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Merck presents new data from ongoing phase 2a clinical trial evaluating the safety, tolerability and pharmacokinetics of investigational, once-monthly, oral islatravir for HIV-1 prevention at IAS 2021

Results from this study support the safety profile of oral islatravir PrEP regimen through 24 weeks versus placebo

 

KENILWORTH, N.J. — (BUSINESS WIRE) — $MRK #MRK–Merck (NYSE: MRK), known as MSD outside the United States and Canada, today announced results from a Phase 2a clinical trial evaluating the safety, tolerability and pharmacokinetics (PK) of six monthly oral doses, over 24 weeks, of islatravir, the company’s investigational nucleoside reverse transcriptase translocation inhibitor, versus placebo for pre-exposure prophylaxis (PrEP) of HIV-1 infection in adults at low-risk of contracting HIV-1. After 24 weeks, once-monthly oral islatravir was generally well tolerated versus placebo. Most adverse events (AEs) were mild and there were no serious drug-related AEs in people who received islatravir. The levels of islatravir in peripheral blood mononuclear cells (PBMCs) also remained above the pre-specified efficacy PK threshold for PrEP at both doses studied (60 mg and 120 mg) eight weeks after the last study dose. These data were shared as a late-breaking oral presentation during the virtual 11th International AIDS Society Conference on HIV Science (IAS 2021) and are a follow-up to the interim analysis that was presented earlier this year at the virtual 2021 HIV Research for Prevention Conference (HIVR4P 2021).

“The 24-week analysis of investigational, once-monthly oral islatravir not only builds upon the PK data we have already seen, but also provides encouraging support for the safety and tolerability profile of this HIV-1 PrEP regimen,” said Dr. Joan Butterton, vice president, global clinical development, infectious diseases, Merck Research Laboratories. “As part of our commitment to understanding the potential for our HIV medicines in a broad range of patients, we focused on the enrollment of diverse patient populations at risk for HIV, including women, who have one of the highest unmet needs in HIV prevention.”

 

Islatravir is currently being evaluated across a variety of dosing regimens, for both the treatment of HIV-1 infection in combination with other antiretroviral agents and for the prevention of HIV-1 infection as a monotherapy. An overview of the islatravir treatment and prevention development program is available here, which includes our two Phase 3 IMPOWER trials evaluating islatravir as once-monthly oral PrEP across diverse populations of people who may benefit from additional HIV-1 prevention options.

 

Phase 2a Oral Study Results for Investigational Islatravir

In the ongoing Phase 2a (NCT04003103) randomized, double-blind, parallel assignment, placebo-controlled, multicenter trial in adults at low-risk for acquiring HIV-1 infection, participants were randomly assigned (2:2:1) to one of three oral once-monthly therapy groups: islatravir 60 mg, islatravir 120 mg or placebo. Participants received once monthly oral doses of islatravir or placebo over a 24-week blinded therapy period, followed by a 12-week blinded follow-up in all groups and a 32-week unblinded follow-up in the islatravir groups to characterize the terminal elimination phase. Outcome measures for safety, tolerability and PK will be analyzed through week 68.

 

Of the 242 randomized participants at this 24-week analysis, which concludes the dosing portion of the study, 92% (n=222/242) completed dosing and 8% (n=20/242) discontinued the study intervention before week 24. Less than 1% (n=2) of participants discontinued due to an AE. Of the total participants, 67.4% (n=163/242) were female, 52.9% (n=128/242) were white, 41.7% (n=101/242) were Black or African American and 14.9% (n=36/242) were Hispanic or Latino. Unblinded safety data showed that both doses of islatravir were generally well tolerated versus placebo over 24 weeks and most AEs were mild (73.5%). The most common AEs (occurring in >5% of participants) in the islatravir 60 mg, islatravir 120 mg and placebo groups respectively were headache (10.3% [n=10/97], 9.3% [n=9/97] and 4.2% [n=2/48]), diarrhea (5.2% [n=5/97], 5.2% [n=5/97] and 8.3% [n=4/48]) and nausea (5.2% [n=5/97]), 7.2% [n=7/97] and 4.2% [n=2/48]). There were no serious drug-related AEs in people who received islatravir. The study enrolled a population at low-risk for HIV infection as evidenced by no confirmed HIV infections occurring during the treatment period.

 

The PK analysis showed that trough concentrations (the lowest level between doses) of islatravir triphosphate in PBMCs following either 60 mg or 120 mg monthly doses continue to remain above the pre-specified PK threshold for HIV-1 prophylaxis of 0.05 pmol/106 PBMCs and were sustained through eight weeks after the last dose of islatravir.

 

About Islatravir (MK-8591)

Islatravir (MK-8591) is Merck’s investigational nucleoside reverse transcriptase translocation inhibitor under evaluation in clinical trials for the treatment of HIV-1 infection in combination with other antiretrovirals, including the ILLUMINATE clinical trials program for once-daily treatment. Islatravir is also being studied for pre-exposure prophylaxis (PrEP) of HIV-1 infection as a single agent across a variety of formulations, including the IMPOWER clinical trials evaluating an oral once-monthly regimen.

 

Our Commitment to HIV

For more than 35 years, Merck has been committed to scientific research and discovery (R&D) in HIV. Today, we are developing a series of antiviral options designed to help people manage HIV and protect people from HIV, with the goal of reducing the growing burden of infection worldwide. We remain committed to working hand-in-hand with our partners in the global HIV community to address the complex challenges that impede progress toward ending the epidemic.

 

About Merck

For 130 years, Merck, known as MSD outside of the United States and Canada, has been inventing for life, bringing forward medicines and vaccines for many of the world’s most challenging diseases in pursuit of our mission to save and improve lives. We demonstrate our commitment to patients and population health by increasing access to health care through far-reaching policies, programs and partnerships. Today, Merck continues to be at the forefront of research to prevent and treat diseases that threaten people and animals – including cancer, infectious diseases such as HIV and Ebola, and emerging animal diseases – as we aspire to be the premier research-intensive biopharmaceutical company in the world. For more information, visit www.merck.com and connect with us on Twitter, Facebook, Instagram, YouTube and LinkedIn.

 

Forward-Looking Statement of Merck & Co., Inc., Kenilworth, N.J., USA

This news release of Merck & Co., Inc., Kenilworth, N.J., USA (the “company”) includes “forward-looking statements” within the meaning of the safe harbor provisions of the U.S. Private Securities Litigation Reform Act of 1995. These statements are based upon the current beliefs and expectations of the company’s management and are subject to significant risks and uncertainties. There can be no guarantees with respect to pipeline products that the products will receive the necessary regulatory approvals or that they will prove to be commercially successful. If underlying assumptions prove inaccurate or risks or uncertainties materialize, actual results may differ materially from those set forth in the forward-looking statements.

 

Risks and uncertainties include but are not limited to, general industry conditions and competition; general economic factors, including interest rate and currency exchange rate fluctuations; the impact of the global outbreak of novel coronavirus disease (COVID-19); the impact of pharmaceutical industry regulation and health care legislation in the United States and internationally; global trends toward health care cost containment; technological advances, new products and patents attained by competitors; challenges inherent in new product development, including obtaining regulatory approval; the company’s ability to accurately predict future market conditions; manufacturing difficulties or delays; financial instability of international economies and sovereign risk; dependence on the effectiveness of the company’s patents and other protections for innovative products; and the exposure to litigation, including patent litigation, and/or regulatory actions.

 

The company undertakes no obligation to publicly update any forward-looking statement, whether as a result of new information, future events or otherwise. Additional factors that could cause results to differ materially from those described in the forward-looking statements can be found in the company’s 2020 Annual Report on Form 10-K and the company’s other filings with the Securities and Exchange Commission (SEC) available at the SEC’s Internet site (www.sec.gov).

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Business

Merck announces U.S. FDA approval of VAXNEUVANCE™ (Pneumococcal 15-valent conjugate vaccine) for the prevention of invasive pneumococcal disease in adults 18 years and older caused by 15 Serotypes

Clinical Data Supporting Approval Demonstrated Non-Inferior Immune Responses for the Serotypes Shared with PCV13 (1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F and 23F)

 VAXNEUVANCE Elicited Superior Immune Responses for Serotypes 3, 22F and 33F Compared to PCV13, Which Are Major Causes of Disease

 

KENILWORTH, N.J. — (BUSINESS WIRE) — $MRK #MRK–(NYSE: MRK), known as MSD outside the United States and Canada, today announced the U.S. Food and Drug Administration (FDA) approved VAXNEUVANCE™ (Pneumococcal 15-valent Conjugate Vaccine) (pronounced VAKS-noo-vans) for active immunization for the prevention of invasive disease caused by Streptococcus pneumoniae serotypes 1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, 22F, 23F and 33F in adults 18 years of age and older. The approval follows the FDA’s Priority Review of Merck’s application. VAXNEUVANCE is contraindicated for individuals with a history of severe allergic reaction (e.g., anaphylaxis) to any component of VAXNEUVANCE or to diphtheria toxoid; see additional Select Safety Information below.

The U.S. Centers for Disease Control and Prevention’s (CDC) Advisory Committee on Immunization Practices (ACIP) is expected to meet in October to discuss and make recommendations on the use of VAXNEUVANCE in adults.

VAXNEUVANCE was approved based on data from seven randomized, double-blind clinical studies assessing safety, tolerability, and immunogenicity in adults (see “Clinical Data Supporting FDA Approval” below for additional details). Clinical data showed that immune responses elicited by VAXNEUVANCE were non-inferior to the currently available 13-valent pneumococcal conjugate vaccine (PCV13) for the 13 shared serotypes, as assessed by opsonophagocytic activity (OPA) Geometric Mean Titers (GMTs).

Additionally, immune responses for VAXNEUVANCE were superior to PCV13 for shared serotype 3 and for the two serotypes unique to VAXNEUVANCE, 22F and 33F. In the pivotal Phase 3 PNEU-AGE (V114-019) study, superiority for VAXNEUVANCE relative to PCV13 was based on statistically significantly greater OPA GMT ratios for serotypes 22F [GMT Ratio 32.52 (95% Confidence Interval (CI) 25.87, 40.88)] and 33F [GMT Ratio 7.19 (95% CI 6.13, 8.43)], as well as for the key secondary objective assessing serotype 3 [GMT Ratio 1.62 (95% CI 1.40, 1.87)]. Randomized controlled trials assessing the clinical efficacy of VAXNEUVANCE compared to PCV13 have not been conducted.

“Some adults, including older adults or those with certain chronic medical conditions or immunocompromising conditions, are at increased risk for pneumococcal disease and its serious, sometimes life-threatening complications,” said Dr. Jose Cardona, Indago Research and Health Center, coordinating investigator for the PNEU-AGE trial. “The FDA’s approval of VAXNEUVANCE is based on robust Phase 2 and 3 studies assessing immune responses in a broad range of adult populations and provides an important new option in protection from invasive pneumococcal disease.”

Pneumococcal disease is an infection caused by bacteria called Streptococcus pneumoniae, or pneumococcus. Different strains of this bacteria are called serotypes. Invasive pneumococcal disease (IPD) occurs when the bacteria infect parts of the body that are usually free from germs. Approximately 80 percent of all adult IPD burden is among adults 50 years of age and older. Serotypes 3, 22F and 33F contribute significantly to the burden of IPD, and serotype 3 is the leading cause of IPD in adults in the U.S.

“At Merck, we are committed to helping protect more people from invasive pneumococcal disease. That’s why we set out to develop a conjugate vaccine that includes pneumococcal serotypes that pose the greatest threat and elicits a strong immune response to each serotype covered,” said Dr. Roy Baynes, senior vice president and head of global clinical development, chief medical officer, Merck Research Laboratories. “The FDA approval of VAXNEUVANCE builds on Merck’s more than 40 years of experience in pneumococcal disease prevention with a new option that includes serotypes responsible for substantial disease burden in adults, like serotype 3, as well as serotypes 22F and 33F, which are associated with a high degree of invasiveness and antibiotic resistance.”

About VAXNEUVANCE

VAXNEUVANCE, Merck’s approved 15-valent pneumococcal conjugate vaccine, consists of purified capsular polysaccharides from S. pneumoniae serotypes 1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, 22F, 23F and 33F individually conjugated to CRM197 carrier protein. VAXNEUVANCE is indicated for active immunization for the prevention of invasive disease caused by the S. pneumoniae serotypes contained in the vaccine. VAXNEUVANCE previously received Breakthrough Therapy designation from the FDA for the prevention of IPD in adults 18 years of age and older. In January 2021, it received Priority Review designation.

Merck is involved in litigation challenging the validity of several Pfizer Inc. patents that relate to pneumococcal vaccine technology in the United States and several foreign jurisdictions.

Select Safety Information for VAXNEUVANCE

Do not administer VAXNEUVANCE to individuals with a severe allergic reaction (e.g., anaphylaxis) to any component of VAXNEUVANCE or to diphtheria toxoid.

Some individuals with altered immunocompetence, including those receiving immunosuppressive therapy, may have a reduced immune response to VAXNEUVANCE.

The most commonly reported solicited adverse reactions in individuals 18 through 49 years of age were: injection site pain (75.8%), fatigue (34.3%), myalgia (28.8%), headache (26.5%), injection site swelling (21.7%), injection site erythema (15.1%) and arthralgia (12.7%).

The most commonly reported solicited adverse reactions in individuals 50 years of age and older were: injection site pain (66.8%), myalgia (26.9%), fatigue (21.5%), headache (18.9%), injection site swelling (15.4%), injection site erythema (10.9%) and arthralgia (7.7%).

Vaccination with VAXNEUVANCE may not protect all vaccine recipients.

Clinical Data Supporting FDA Approval

VAXNEUVANCE was approved based on data from seven randomized, double-blind clinical studies designed to evaluate its safety, tolerability, and immunogenicity in 7,438 individuals from a variety of adult populations and clinical circumstances, 5,630 of whom received VAXNEUVANCE. These included studies of:

  • Healthy adults 50 years of age and older. The pivotal Phase 3 active comparator-controlled study assessed serotype-specific OPA responses for each of the 15 serotypes contained in VAXNEUVANCE at 30 days post-vaccination in pneumococcal vaccine naïve participants randomized to receive either VAXNEUVANCE (n=604) or PCV13 (n=601) (V114-019/PNEU-AGE [NCT03950622]). The study demonstrated that VAXNEUVANCE was non-inferior to PCV13 for the 13 shared serotypes and induces statistically significantly greater OPA GMTs compared to PCV13 for shared serotype 3 and for the two unique serotypes (22F, 33F).
  • Adults 18-49 years of age with no history of pneumococcal vaccination, including individuals at increased risk of developing pneumococcal disease.

A Phase 3 descriptive study included individuals with stable underlying medical conditions (e.g., diabetes mellitus, renal disorders, chronic heart disease, chronic liver disease, chronic lung disease including asthma) and/or behavioral risk factors (e.g., smoking, increased alcohol use) that increased their risk of developing pneumococcal disease. Participants were randomized to receive VAXNEUVANCE (n=1,135) or PCV13 (n=380), followed by PNEUMOVAX® 23 (pneumococcal vaccine polyvalent) six months later (V114-017/PNEU-DAY [NCT03547167]). VAXNEUVANCE elicited immune responses to all 15 serotypes as assessed by OPA GMTs at 30 days following vaccination. Additionally, following vaccination with PNEUMOVAX 23, the OPA GMTs for the 15 serotypes in VAXNEUVANCE were numerically similar among subjects who had received VAXNEUVANCE or PCV13 for the first vaccination.

  • Adults living with HIV, an immunocompromising condition. A Phase 3 descriptive study assessed the use of VAXNEUVANCE in pneumococcal vaccine naïve HIV-infected adults 18 years of age and older with CD4+ T cell count ≥50 cells per microliter and plasma HIV RNA value <50,000 copies/mL (V114-018/PNEU- WAY [NCT03480802]). Participants were randomized to receive VAXNEUVANCE (n=152) or PCV13 (n=150), followed by PNEUMOVAX 23 two months later. OPA GMTs were higher after administration of VAXNEUVANCE, compared to pre-vaccination, for the 15 serotypes contained in VAXNEUVANCE. After sequential administration with PNEUMOVAX 23, OPA GMTs were numerically similar between the two vaccination groups for all 15 serotypes contained in VAXNEUVANCE.
  • Co-administration of VAXNEUVANCE with seasonal quadrivalent influenza vaccine (QIV). A Phase 3 trial evaluated adults 50 years of age and older who were randomized to receive VAXNEUVANCE concomitantly with a seasonal inactivated QIV (Fluarix Quadrivalent) (n=600) or non-concomitantly 30 days after QIV (n=600) (V114-021/PNEU-FLU [NCT03615482]). The non-inferiority criteria for the comparisons of GMTs were met for the 15 pneumococcal serotypes in VAXNEUVANCE and for the 4 influenza vaccine strains tested. VAXNEUVANCE can be administered concomitantly with seasonal inactivated influenza vaccine.
  • Use of VAXNEUVANCE as part of a sequential regimen with PNEUMOVAX 23.

A Phase 3 active comparator-controlled descriptive study in pneumococcal vaccine-naïve adults 50 years of age or older assessed the use of VAXNEUVANCE (n=327) or PCV13 (n=325), followed by PNEUMOVAX 23 one year later (V114-016/PNEU-PATH [NCT03480763]). Following vaccination with PNEUMOVAX 23, OPA GMTs were numerically similar between the two vaccination groups for the 15 serotypes in VAXNEUVANCE.

About Merck

For 130 years, Merck, known as MSD outside of the United States and Canada, has been inventing for life, bringing forward medicines and vaccines for many of the world’s most challenging diseases in pursuit of our mission to save and improve lives. We demonstrate our commitment to patients and population health by increasing access to health care through far-reaching policies, programs and partnerships. Today, Merck continues to be at the forefront of research to prevent and treat diseases that threaten people and animals – including cancer, infectious diseases such as HIV and Ebola, and emerging animal diseases – as we aspire to be the premier research-intensive biopharmaceutical company in the world. For more information, visit www.merck.com and connect with us on Twitter, Facebook, Instagram, YouTube and LinkedIn.

Forward-Looking Statement of Merck & Co., Inc., Kenilworth, N.J., USA

This news release of Merck & Co., Inc., Kenilworth, N.J., USA (the “company”) includes “forward-looking statements” within the meaning of the safe harbor provisions of the U.S. Private Securities Litigation Reform Act of 1995. These statements are based upon the current beliefs and expectations of the company’s management and are subject to significant risks and uncertainties. There can be no guarantees with respect to pipeline products that the products will receive the necessary regulatory approvals or that they will prove to be commercially successful. If underlying assumptions prove inaccurate or risks or uncertainties materialize, actual results may differ materially from those set forth in the forward-looking statements.

Risks and uncertainties include but are not limited to, general industry conditions and competition; general economic factors, including interest rate and currency exchange rate fluctuations; the impact of the global outbreak of novel coronavirus disease (COVID-19); the impact of pharmaceutical industry regulation and health care legislation in the United States and internationally; global trends toward health care cost containment; technological advances, new products and patents attained by competitors; challenges inherent in new product development, including obtaining regulatory approval; the company’s ability to accurately predict future market conditions; manufacturing difficulties or delays; financial instability of international economies and sovereign risk; dependence on the effectiveness of the company’s patents and other protections for innovative products; and the exposure to litigation, including patent litigation, and/or regulatory actions.

The company undertakes no obligation to publicly update any forward-looking statement, whether as a result of new information, future events or otherwise. Additional factors that could cause results to differ materially from those described in the forward-looking statements can be found in the company’s 2020 Annual Report on Form 10-K and the company’s other filings with the Securities and Exchange Commission (SEC) available at the SEC’s Internet site (www.sec.gov).

Please see Prescribing Information for VAXNEUVANCE (pneumococcal 15-valent conjugate vaccine) at https://www.merck.com/product/usa/pi_circulars/v/vaxneuvance/vaxneuvance_pi.pdf.

and Patient Information at https://www.merck.com/product/usa/pi_circulars/v/vaxneuvance/vaxneuvance_ppi.pdf.

Brands mentioned are trademarks of their respective owners.

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Media Contacts:

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Steve Wanczyk

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Investor Contacts:

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Business

AM Best maintains under review with negative implications status for credit ratings of Watford Re Ltd. and its subsidiaries

OLDWICK, N.J. — (BUSINESS WIRE) — #insurance—AM Best has maintained the under review with negative implications status for the Financial Strength Rating of A- (Excellent) and the Long-Term Issuer Credit Ratings (Long-Term ICR) of “a-” (Excellent) of Watford Re Ltd. (Watford Re) (Bermuda) and its subsidiaries, Watford Insurance Company Europe Limited (WICE) (Gibraltar), Watford Insurance Company (WIC) (New Jersey) and Watford Specialty Insurance Company (WSIC) (New Jersey). In addition, AM Best has maintained the under review with negative implications status for the Long-Term ICR of “bbb-” (Good) and the Long-Term Issue Credit Rating of “bb” (Fair) on the $225 million ($52 million outstanding) 8.5% cumulative preference shares of Watford Holdings Ltd. (Watford) (Bermuda) [NASDAQ: WTRE], the group’s ultimate holding company.

This Credit Rating (rating) action considers the recent announcement that Arch Capital Group Ltd. (Arch) has completed its merger agreement with Watford. Arch has assigned its interests and obligations under the merger agreement to a newly formed entity, Greysbridge Holdings Ltd., under which Arch owns approximately a 40% stake, with funds managed by Warburg Pincus LLC and Kelso & Company, each owning approximately 30%.

AM Best acknowledges that the transaction with Arch could benefit the Watford group through potential further de-risking of its investment portfolio, removing the burden of public company status, and possible rating enhancement stemming from being a member of a large, well-diversified group. However, although the transaction has closed, the ultimate impact to Watford’s ratings will be determined when AM Best has met with management and analyzed the group’s business plans, including an analysis of future investment risk, financial projections and operating structure within the Arch group. The under review status therefore is expected to be resolved following these discussions. AM Best will continue to evaluate Watford’s balance sheet strength, operating performance and enterprise risk management to assess that it stays in line with projected amounts.

This press release relates to Credit Ratings that have been published on AM Best’s website. For all rating information relating to the release and pertinent disclosures, including details of the office responsible for issuing each of the individual ratings referenced in this release, please see AM Best’s Recent Rating Activity web page. For additional information regarding the use and limitations of Credit Rating opinions, please view Guide to Best’s Credit Ratings. For information on the proper use of Best’s Credit Ratings, Best’s Preliminary Credit Assessments and AM Best press releases, please view Guide to Proper Use of Best’s Ratings & Assessments.

AM Best is a global credit rating agency, news publisher and data analytics provider specializing in the insurance industry. Headquartered in the United States, the company does business in over 100 countries with regional offices in London, Amsterdam, Dubai, Hong Kong, Singapore and Mexico City. For more information, visit www.ambest.com.

Copyright © 2021 by A.M. Best Rating Services, Inc. and/or its affiliates. ALL RIGHTS RESERVED.

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Business Sports & Gaming

Fubo Gaming, The Cordish Companies announce completion of market access agreement in Pennsylvania for forthcoming mobile Fubo Sportsbook

Fubo Gaming Now Holds Market Access Deals in 4 States

 

NEW YORK — (BUSINESS WIRE) — Fubo Gaming, a subsidiary of leading sports-first live TV streaming platform fuboTV Inc. (NYSE: FUBO), and The Cordish Companies announced today the completion of a market access agreement for the forthcoming mobile Fubo Sportsbook in Pennsylvania. Fubo Gaming’s agreement with The Cordish Companies, owner and operator of Live! Casino & Hotel Philadelphia and Live! Casino Pittsburgh, provides for state-wide mobile access for both sports betting and iGaming. The launch of Fubo Sportsbook in Pennsylvania is subject to obtaining requisite regulatory approvals.

Through Fubo Sportsbook, fuboTV intends to integrate gaming with its expansive live sports offering for a seamless user experience enabling consumers to wager while they watch. fuboTV currently has a leading sports offering in Pennsylvania through its carriage agreements with regional sports networks NBC Sports Philadelphia (Philadelphia 76ers, Philadelphia Flyers, Philadelphia Phillies) and AT&T SportsNet Pittsburgh (Pittsburgh Penguins, Pittsburgh Pirates), in addition to local and national network coverage.

 

Today’s agreement in Pennsylvania will bring Fubo Sportsbook to a minimum of four states following previously announced market access agreements in New Jersey and Indiana (through Caesars Entertainment, Inc.) and Iowa (through Casino Queen). Fubo Sportsbook is expected to begin rolling out state-by-state in the fourth quarter 2021, subject to obtaining requisite regulatory approvals in each jurisdiction.

 

“Entering Pennsylvania, one of the largest sports betting and iGaming makers in the U.S., is a significant accomplishment for our forthcoming Fubo Sportsbook which, in this market, can also include mobile casino games,” said Scott Butera, president, Fubo Gaming. “We are also excited to be partnering with Cordish who has been a leader in gaming and sports entertainment for decades.”

 

“Our agreement with The Cordish Companies will bring Fubo Sportsbook to consumers in Pennsylvania, expanding our sportsbook’s reach to at least four states,” said David Gandler, co-founder and CEO, fuboTV. “With our sportsbook, we’re looking forward to delivering a comprehensive sports entertainment experience that combines live streaming and wagering. We expect to launch Fubo Sportsbook in the fourth quarter of this year pending regulatory approvals.”

 

“Partnering with Fubo Gaming to bring our guests this exciting, integrated mobile sports betting option is the natural evolution of our Live! Casino brands in Pennsylvania,” said Rob Norton, president, Cordish Gaming Group. “Philadelphia and Pittsburgh are both iconic sports cities that are deserving of best-in-class sports betting platforms, so we look forward to working with Fubo Gaming on this new endeavor.”

 

About The Cordish Companies

The Cordish Companies’ origins date back to 1910 and encompass four generations of privately-held, family ownership. During the past ten decades, The Cordish Companies has grown into a global leader in Commercial Real Estate; Entertainment Districts; Sports-Anchored Developments; Gaming; Hotels; Residential Properties; Restaurants; International Development; Coworking Spaces; and Private Equity. One of the largest and most respected developers in the world, The Cordish Companies has been awarded an unprecedented seven Urban Land Institute Awards for Excellence for public-private developments that are of unique significance to the cities in which they are located. The Cordish Companies has developed and operates highly acclaimed dining, entertainment and hospitality destinations throughout the United States, many falling under The Cordish Companies’ Live! Brand, highly regarded as one of the premier entertainment brands in the country. In gaming, The Cordish Companies has developed among the most successful casino hotel resorts in the world including the Hard Rock Hotel & Casino Hollywood, Hard Rock Hotel & Casino Tampa and Live! Casino & Hotel Maryland. Welcoming over 55 million visitors per year, these developments are among the highest profile dining, entertainment, gaming, hotel and sports-anchored destinations in the country. Over the generations, The Cordish Companies has remained true to the family’s core values of quality, entrepreneurial spirit, long-term personal relationships, and integrity. As a testimony to the long-term vision of its family leadership, The Cordish Companies still owns and manages virtually every business it has created. For more information visit www.cordish.com or follow us on Twitter.

 

“The Cordish Companies,” “The Cordish Company” and “Cordish” are trademarks used under license by independent corporations, legal liability companies and partnerships (“Cordish Entities”). Each Cordish Entity is a separate, single-purpose legal entity that is solely responsible for its obligations and liabilities. No common operations or financial interdependency, and no intermingling of assets or liabilities of the Cordish Entities exists, or should be deemed to exist, as a result of the potential common reference to multiple independent entities operating under the names “Cordish,” “The Cordish Companies” or “The Cordish Company” here or elsewhere.

 

About Fubo Gaming

Fubo Gaming Inc. is a subsidiary of fuboTV Inc. (NYSE: FUBO) that launched in 2021. Complementing fuboTV’s leading sports streaming platform, Fubo Gaming aims to provide a comprehensive sports entertainment experience through sports betting and interactive gaming. The online wagering experience, Fubo Sportsbook, is expected to launch in Q4 2021, subject to obtaining requisite regulatory approvals. Fubo Gaming is based in Chicago.

 

About fuboTV

With a mission to provide the world’s most thrilling sports-first live TV experience through the greatest breadth of premium content, interactivity and integrated wagering, fuboTV Inc. (NYSE: FUBO) is focused on bringing to life its vision of a streaming platform that transcends the industry’s current virtual MVPD model. fuboTV Inc. operates in the U.S., Canada and Spain.

Leveraging its proprietary data and technology platform optimized for live TV and sports viewership, fuboTV Inc. aims to turn passive viewers into active participants and define a new category of interactive television. Through its cable TV replacement product, fuboTV, subscribers can stream a broad mix of 100+ live TV channels, including 74 of the top 100 Nielsen-ranked networks across sports, news and entertainment — more than any other live TV streaming platform (source: Nielsen Total Viewers, 2020). fuboTV intends to add interactivity to its streaming experience with the launch of predictive free-to-play gaming in Q3 2021.

Fubo Gaming Inc., a subsidiary of fuboTV Inc., expects to launch Fubo Sportsbook, a comprehensive sports entertainment experience through sports betting and interactive gaming, in Q4 2021, subject to obtaining requisite regulatory approvals.

 

Forward-Looking Statements

This letter contains forward-looking statements of fuboTV Inc. (“fuboTV”) that involve substantial risks and uncertainties. All statements contained in this press release are forward-looking statements within the meaning of The Private Securities Litigation Reform Act of 1995. The words “could,” “will,” “plan,” “intend,” “anticipate,” “approximate,” “expect,” “potential,” or the negative of these terms or other similar expressions are intended to identify forward-looking statements, although not all forward-looking statements contain these identifying words. Actual results or events could differ materially from the plans, intentions and expectations disclosed in the forward-looking statements that fuboTV makes due to a number of important factors, including (i) risks related to the ability to realize the anticipated benefits of the Balto and Vigtory acquisitions, (ii) risks related to the company’s access to capital and fundraising prospects to fund its ongoing operations, (iii) risks related to diverting management’s attention from fuboTV’s ongoing business operations to address integration and fundraising efforts, (iv) risks related to our ability to capitalize successfully on market trends and develop and market a sports wagering offering, and (v) other business effects, including the effects of industry, market, economic, political or regulatory conditions, future exchange and interest rates, and changes in tax and other laws, regulations, rates and policies, including the impact of COVID-19 on the broader market. Further risks that could cause actual results to differ materially from those matters expressed in or implied by such forward-looking statements are discussed in the company’s periodic filings with the Securities and Exchange Commission and we encourage you to read such risks in detail. The forward-looking statements in this press release represent fuboTV’s views as of the date of this press release. fuboTV anticipates that subsequent events and developments will cause its views to change. However, while it may elect to update these forward-looking statements at some point in the future, it specifically disclaims any obligation to do so. You should, therefore, not rely on these forward-looking statements as representing fuboTV’s views as of any date subsequent to the date of this letter.

Contacts

Investor Contact:

The Blueshirt Group for fuboTV

ir@fubo.tv

Media Contacts:

Jennifer L. Press, fuboTV

jpress@fubo.tv

Katie Minogue, fuboTV

kminogue@fubo.tv

Cari Furman, The Cordish Companies

cfurman@cordish.com

Carmen Gonzales, Live! Casinos & Hotels

Carmen.Gonzales@livech.com

Categories
Business Technology

Dahua technology joins efforts with moms in Security Global Outreach to help end human trafficking

IRVINE, Calif. — (BUSINESS WIRE) — #1080p–Global leader in video surveillance and security technology, Dahua, was proud to sponsor the first ever Moms in Security Global Outreach (MISGO) Golf Outing. The inaugural charity golf event, held on June 21, 2021 in Lincoln Park, New Jersey, aimed to raise funds for organizations that fight human trafficking. Dahua was happy to join other industry sponsors in donating to and participating in the first of its kind event.

Dahua’s generous donation was dispersed among various non-profit organizations, all committed to either preventing, ending, or bringing awareness to the child trafficking epidemic. Beneficiaries of the MISGO Golf Outing include Operation Underground Railroad, Prevent Child Abuse New Jersey, and Veterans For Child Rescue. Dahua’s investment in these local and national causes underlines their dedication to the US market.

 

This kind of dedication did not go unnoticed by the event organizer, Elisa Mula, who also serves as the anti-human trafficking task force leader for the New York chapter of Women In International Security. “We are so pleased that Dahua really stepped up and supported and sponsored our MISGO event,” said Mula. “It really couldn’t have even happened without sponsors like them, so we were just so happy to have an industry leader like Dahua put their name behind our first golf event.”

 

Likewise, Dahua was more than willing to support such a great cause. “It was a great event and at the end of the day, it was all for a great cause,” said Tim Wang, President and CEO for Dahua Technology USA. “We can’t wait for next year’s golf outing!”

 

 

About Dahua Technology

Dahua Technology is a world-leading, video-centric smart IoT solution and service provider. Since the launch of the industry’s first self-developed 8-channel embedded DVR in 2002, Dahua Technology has devoted itself to technological innovation and has been continuously increasing its investment in R&D. Dahua Technology brings high-value, total security solutions to the market by focusing on integrity and personal relationships to enhance the customer experience. Our surveillance solutions, ranging from award-winning cameras to video management software, deliver unparalleled quality, reliability, and stability.

 

 

About Moms in Security Global Outreach

Seeing a need for collaboration between those rescuing children around the world and those with resources in the security world, we formed our organization to make an impact in the area of human trafficking.

 

We focus on making the maximum positive effort for the rescue and protection of our most vulnerable and precious asset, our children. There is nothing more heart wrenching than a child in a tragic situation. And there is nothing more heartwarming and uplifting than seeing them recovered. We are committed to shining a light on those efforts, raising funds to recover more children and to putting the “Heart” back into the security industry.

Contacts

Press Contact
Defined Marketing

Janet Dabice Fenner

jfenner@definedmktg.com

Categories
Entertainment News

Tiger Balm U.S. videos win six coveted Telly Awards for excellence

Awards are the latest milestone in brand’s continued sales and marketing momentum

 

LIVERMORE, Calif. — (BUSINESS WIRE) — Prince of Peace Enterprises, Inc., the sole United States distributor for all Tiger Balm pain-relieving products, is proud to announce that online commercials and social videos supporting its products earned six trophies from this year’s 42nd Annual Telly Awards.


Founded in 1979, the Telly Awards are the world’s largest honor for video content across television and all screens, and are judged by leaders from entertainment, publishing, advertising, and emerging technology. Nearly 15,000 submissions were entered this year from all 50 states and 5 continents. Winners represent some of the world’s most respected advertising agencies, television stations, production companies, and publishers.

 

Tiger Balm videos won three Gold Awards and three Silver Awards, including the only two Gold awards presented in the Social Video: Art Direction category:

  • Gold, Social Video: Art Direction – Tiger Balm “Professional Basketball Player Jeremy Lin Behind the Scenes” (Official Listing)
  • Gold, Social Video: Art Direction – Tiger Balm “Kristin Allen Acrobatic Gymnast Behind the Scenes” (Official Listing)
  • Gold, Social Video: Editing – Tiger Balm “Kristin Allen Acrobatic Gymnast Behind the Scenes” (Official Listing)
  • Silver, Social Video: Health & Wellness – Tiger Balm “Professional Basketball Player Jeremy Lin Behind the Scenes” (Official Listing)
  • Silver, Social Video: Editing – Tiger Balm “Professional Basketball Player Jeremy Lin Behind the Scenes” (Official Listing)
  • Silver, Social Video: Health & Wellness – Tiger Balm “Kristin Allen Acrobatic Gymnast Behind the Scenes” (Official Listing)

 

The videos were produced by Inception Marketing, Inc., a leading San Francisco Bay Area-based marketing communications firm that is Prince of Peace’s official advertising agency of record.

 

Continuing growth for Tiger Balm U.S.

Even with a radically altered landscape during the past year, Tiger Balm has seen strong continuous sales growth in the United States for over two decades. Tiger Balm products are sold in more retail channels across the country than any other external analgesics brand, a testament to the popularity the brand enjoys among consumers seeking topical pain relief for their aches and pains. Additionally, its flagship product – Tiger Balm Ultra Strength Ointment – is the top-selling pain-relieving ointment in the United States, according to IRI.

“The ongoing collaboration between the Prince of Peace and Inception Marketing teams has driven the Tiger Balm brand to new levels of success in the United States,” said Kenneth Yeung, Founder and President of Prince of Peace. “Since partnering with Inception over ten years ago, we have produced consistently innovative creative, developed a loyal social media fan base, and have attracted widely-respected and influential brand ambassadors who are passionate about the Tiger Balm brand and product offerings.”

 

World-Class Brand Ambassadors

The award-winning videos feature pro basketball favorite Jeremy Lin and Hall of Fame American acrobatic gymnast Kristin Allen, two elite athletes who choose Tiger Balm from a crowded field of pain relievers to stay at the top of their game and recover from strenuous activities.

Tiger Balm U.S. has a history of developing marketing campaigns with world-class athletes. Previous influential Brand Ambassadors have included NFL standouts, Joe Montana and Jerry Rice, three-time World Champion and two-time U.S. Olympic Gold Medalist Christian Taylor, professional flatland BMX rider Terry Adams, and World Champion Rock Climber Sasha DiGiulian.

 

About Inception Marketing

With over 40 years of proven independent advertising agency experience, Inception Marketing, Inc. (www.inceptionus.com) works with clients of all sizes to take their brands further. Inception has created integrated marketing campaigns for global, national, and regional accounts, from Singapore to SOMA, in a wide range of categories across all media channels. Inception is located in the San Francisco Bay Area.

 

About Tiger Balm U.S.

Prince of Peace Enterprises, Inc. (http://www.popus.com) introduced the world-famous Tiger Balm brand to the United States mainstream market in 1986 and has been the sole licensed U.S. distributor for all Tiger Balm products since. Prince of Peace is headquartered in the heart of the San Francisco Bay Area, CA with additional branch offices in New Jersey, Los Angeles, Hong Kong, and Guang Zhou China.

Tiger Balm U.S. (http://www.tigerbalm.com/us) can be found on Facebook (www.facebook.com/TigerBalmUS), Twitter (www.twitter.com/Tiger_Balm_US), and Instagram (www.instagram.com/tiger_balm_us).

Contacts

Steve Stamates

415-399-1045

Steve@inceptionus.com

Categories
Local News Science

Bristol Myers Squibb provides update on CheckMate -651 trial evaluating Opdivo (nivolumab) plus Yervoy (ipilimumab) versus EXTREME regimen as first-line treatment for squamous cell carcinoma of the head and neck

PRINCETON, N.J. — (BUSINESS WIRE) — $BMY #CheckMate—Bristol Myers Squibb (NYSE: BMY) today announced an update on the Phase 3 CheckMate -651 trial comparing Opdivo (nivolumab) plus Yervoy (ipilimumab) to the EXTREME regimen (cetuximab, cisplatin/carboplatin and fluorouracil) as a first-line treatment in platinum-eligible patients with recurrent or metastatic squamous cell carcinoma of the head and neck (SCCHN). Although Opdivo plus Yervoy showed a clear, positive trend towards overall survival (OS) in patients whose tumors express PD-L1 with a combined positive score (CPS) ≥ 20, the study did not meet its primary endpoints. The safety profile of Opdivo and Yervoy in this trial was consistent with previously reported studies in solid tumors.

“Numerous studies have shown long-term survival improvements with the Opdivo plus Yervoy combination across various tumor types, bringing benefit to patients around the world,” said Abderrahim Oukessou, M.D., vice president, thoracic cancers, development lead, Bristol Myers Squibb. “In the CheckMate -651 trial, Opdivo plus Yervoy showed a positive overall survival trend relative to EXTREME in patients with squamous cell carcinoma of the head and neck whose tumors express PD-L1, despite the control arm performing better than expected based on historical data. We are disappointed that these results did not reach statistical significance, and we remain committed to advancing research and supporting patients with this difficult-to-treat cancer.”

 

Opdivo monotherapy previously demonstrated a survival benefit in adults with recurrent or metastatic SCCHN after platinum-based therapy in the CheckMate -141 trial. Based on these results, the U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA) approved Opdivo for this indication in 2016.

 

In addition, Opdivo plus Yervoy-based combinations have shown significant improvements in OS in six Phase 3 clinical trials in five different tumors to date: non-small cell lung cancer, metastatic melanoma, advanced renal cell carcinoma, malignant pleural mesothelioma and esophageal squamous cell carcinoma.

 

Bristol Myers Squibb thanks the patients and investigators involved in the CheckMate -651 clinical trial. The company will complete a full evaluation of the data and work with investigators to share the results with the scientific community.

 

About CheckMate -651

CheckMate -651 is a Phase 3 randomized, multi-center study evaluating Opdivo 3 mg/kg every two weeks in combination with Yervoy 1 mg/kg every six weeks compared with the EXTREME regimen of cetuximab, cisplatin/carboplatin and fluorouracil as a first-line treatment in patients with recurrent or metastatic squamous cell carcinoma of the head and neck (SCCHN). The dual primary endpoints of the trial are overall survival (OS) in the all-randomized (i.e. intent-to-treat) population and OS in patients whose tumors express PD-L1 with a CPS ≥ 20. Secondary endpoints include OS in patients with PD-L1-expressing tumors at different cut-off values, objective response rate, duration of response and progression-free survival in all patients and in those with PD-L1-expressing tumors.

 

About Head & Neck Cancer

Head and neck cancer refers to a group of cancers that start in the head and neck, usually in the squamous cells that line the moist mucosal surfaces in this region of the body, like those on the inside of the mouth, nose and throat. Head and neck cancer is the sixth most common cancer globally, with an estimated 930,000 new cases diagnosed and more than 467,000 related deaths per year. Squamous cell carcinoma of the head and neck (SCCHN) accounts for more than 90% of all head and neck cancers. Risk factors for SCCHN can be behavioral, including tobacco or alcohol consumption, or viral, related to human papillomavirus (HPV).

 

Bristol Myers Squibb: Creating a Better Future for People with Cancer

Bristol Myers Squibb is inspired by a single vision — transforming patients’ lives through science. The goal of the company’s cancer research is to deliver medicines that offer each patient a better, healthier life and to make cure a possibility. Building on a legacy across a broad range of cancers that have changed survival expectations for many, Bristol Myers Squibb researchers are exploring new frontiers in personalized medicine, and through innovative digital platforms, are turning data into insights that sharpen their focus. Deep scientific expertise, cutting-edge capabilities and discovery platforms enable the company to look at cancer from every angle. Cancer can have a relentless grasp on many parts of a patient’s life, and Bristol Myers Squibb is committed to taking actions to address all aspects of care, from diagnosis to survivorship. Because as a leader in cancer care, Bristol Myers Squibb is working to empower all people with cancer to have a better future.

 

About Opdivo

Opdivo is a programmed death-1 (PD-1) immune checkpoint inhibitor that is designed to uniquely harness the body’s own immune system to help restore anti-tumor immune response. By harnessing the body’s own immune system to fight cancer, Opdivo has become an important treatment option across multiple cancers.

 

Opdivo’s leading global development program is based on Bristol Myers Squibb’s scientific expertise in the field of Immuno-Oncology and includes a broad range of clinical trials across all phases, including Phase 3, in a variety of tumor types. To date, the Opdivo clinical development program has treated more than 35,000 patients. The Opdivo trials have contributed to gaining a deeper understanding of the potential role of biomarkers in patient care, particularly regarding how patients may benefit from Opdivo across the continuum of PD-L1 expression.

 

In July 2014, Opdivo was the first PD-1 immune checkpoint inhibitor to receive regulatory approval anywhere in the world. Opdivo is currently approved in more than 65 countries, including the United States, the European Union, Japan and China. In October 2015, the Company’s Opdivo and Yervoy combination regimen was the first Immuno-Oncology combination to receive regulatory approval for the treatment of metastatic melanoma and is currently approved in more than 50 countries, including the United States and the European Union.

 

About Yervoy

Yervoy is a recombinant, human monoclonal antibody that binds to the cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4). CTLA-4 is a negative regulator of T-cell activity. Yervoy binds to CTLA-4 and blocks the interaction of CTLA-4 with its ligands, CD80/CD86. Blockade of CTLA-4 has been shown to augment T-cell activation and proliferation, including the activation and proliferation of tumor infiltrating T-effector cells. Inhibition of CTLA-4 signaling can also reduce T-regulatory cell function, which may contribute to a general increase in T-cell responsiveness, including the anti-tumor immune response. On March 25, 2011, the U.S. Food and Drug Administration (FDA) approved Yervoy 3 mg/kg monotherapy for patients with unresectable or metastatic melanoma. Yervoy is approved for unresectable or metastatic melanoma in more than 50 countries. There is a broad, ongoing development program in place for Yervoy spanning multiple tumor types.

 

INDICATIONS

OPDIVO® (nivolumab), as a single agent, is indicated for the treatment of patients with unresectable or metastatic melanoma.

OPDIVO® (nivolumab), in combination with YERVOY® (ipilimumab), is indicated for the treatment of patients with unresectable or metastatic melanoma.

OPDIVO® (nivolumab), in combination with YERVOY® (ipilimumab), is indicated for the first-line treatment of adult patients with metastatic non-small cell lung cancer (NSCLC) whose tumors express PD-L1 (≥1%) as determined by an FDA-approved test, with no EGFR or ALK genomic tumor aberrations.

OPDIVO® (nivolumab), in combination with YERVOY® (ipilimumab) and 2 cycles of platinum-doublet chemotherapy, is indicated for the first-line treatment of adult patients with metastatic or recurrent non-small cell lung cancer (NSCLC), with no EGFR or ALK genomic tumor aberrations.

OPDIVO® (nivolumab) is indicated for the treatment of patients with metastatic non-small cell lung cancer (NSCLC) with progression on or after platinum-based chemotherapy. Patients with EGFR or ALK genomic tumor aberrations should have disease progression on FDA-approved therapy for these aberrations prior to receiving OPDIVO.

OPDIVO® (nivolumab), in combination with YERVOY® (ipilimumab), is indicated for the first-line treatment of adult patients with unresectable malignant pleural mesothelioma (MPM).

OPDIVO® (nivolumab), in combination with YERVOY® (ipilimumab), is indicated for the first-line treatment of patients with intermediate or poor risk advanced renal cell carcinoma (RCC).

OPDIVO® (nivolumab), in combination with cabozantinib, is indicated for the first-line treatment of patients with advanced renal cell carcinoma (RCC).

OPDIVO® (nivolumab) is indicated for the treatment of patients with advanced renal cell carcinoma (RCC) who have received prior anti-angiogenic therapy.

OPDIVO® (nivolumab) is indicated for the treatment of adult patients with classical Hodgkin lymphoma (cHL) that has relapsed or progressed after autologous hematopoietic stem cell transplantation (HSCT) and brentuximab vedotin or after 3 or more lines of systemic therapy that includes autologous HSCT. This indication is approved under accelerated approval based on overall response rate. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.

OPDIVO® (nivolumab) is indicated for the treatment of patients with recurrent or metastatic squamous cell carcinoma of the head and neck (SCCHN) with disease progression on or after platinum-based therapy.

OPDIVO® (nivolumab) is indicated for the treatment of patients with locally advanced or metastatic urothelial carcinoma who have disease progression during or following platinum-containing chemotherapy or have disease progression within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy. This indication is approved under accelerated approval based on tumor response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.

OPDIVO® (nivolumab), as a single agent, is indicated for the treatment of adult and pediatric (12 years and older) patients with microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) metastatic colorectal cancer (CRC) that has progressed following treatment with a fluoropyrimidine, oxaliplatin, and irinotecan. This indication is approved under accelerated approval based on overall response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.

OPDIVO® (nivolumab), in combination with YERVOY® (ipilimumab), is indicated for the treatment of adults and pediatric patients 12 years and older with microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) metastatic colorectal cancer (CRC) that has progressed following treatment with a fluoropyrimidine, oxaliplatin, and irinotecan. This indication is approved under accelerated approval based on overall response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.

OPDIVO® (nivolumab) is indicated for the treatment of patients with hepatocellular carcinoma (HCC) who have been previously treated with sorafenib. This indication is approved under accelerated approval based on overall response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.

OPDIVO® (nivolumab), in combination with YERVOY® (ipilimumab), is indicated for the treatment of patients with hepatocellular carcinoma (HCC) who have been previously treated with sorafenib. This indication is approved under accelerated approval based on overall response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.

OPDIVO® (nivolumab) is indicated for the adjuvant treatment of patients with melanoma with involvement of lymph nodes or metastatic disease who have undergone complete resection.

OPDIVO® (nivolumab) is indicated for the treatment of patients with unresectable advanced, recurrent or metastatic esophageal squamous cell carcinoma (ESCC) after prior fluoropyrimidine- and platinum-based chemotherapy.

OPDIVO® (nivolumab) is indicated for the adjuvant treatment of completely resected esophageal or gastroesophageal junction cancer with residual pathologic disease in patients who have received neoadjuvant chemoradiotherapy (CRT).

OPDIVO® (nivolumab), in combination with fluoropyrimidine- and platinum-containing chemotherapy, is indicated for the treatment of patients with advanced or metastatic gastric cancer, gastroesophageal junction cancer, and esophageal adenocarcinoma.

 

 

IMPORTANT SAFETY INFORMATION

Severe and Fatal Immune-Mediated Adverse Reactions

 

Immune-mediated adverse reactions listed herein may not include all possible severe and fatal immune-mediated adverse reactions.

 

Immune-mediated adverse reactions, which may be severe or fatal, can occur in any organ system or tissue. While immune-mediated adverse reactions usually manifest during treatment, they can also occur after discontinuation of OPDIVO or YERVOY. Early identification and management are essential to ensure safe use of OPDIVO and YERVOY. Monitor for signs and symptoms that may be clinical manifestations of underlying immune-mediated adverse reactions. Evaluate clinical chemistries including liver enzymes, creatinine, adrenocorticotropic hormone (ACTH) level, and thyroid function at baseline and periodically during treatment with OPDIVO and before each dose of YERVOY. In cases of suspected immune-mediated adverse reactions, initiate appropriate workup to exclude alternative etiologies, including infection. Institute medical management promptly, including specialty consultation as appropriate.

 

Withhold or permanently discontinue OPDIVO and YERVOY depending on severity (please see section 2 Dosage and Administration in the accompanying Full Prescribing Information). In general, if OPDIVO or YERVOY interruption or discontinuation is required, administer systemic corticosteroid therapy (1 to 2 mg/kg/day prednisone or equivalent) until improvement to Grade 1 or less. Upon improvement to Grade 1 or less, initiate corticosteroid taper and continue to taper over at least 1 month. Consider administration of other systemic immunosuppressants in patients whose immune-mediated adverse reactions are not controlled with corticosteroid therapy. Toxicity management guidelines for adverse reactions that do not necessarily require systemic steroids (e.g., endocrinopathies and dermatologic reactions) are discussed below.

 

Immune-Mediated Pneumonitis

 

OPDIVO and YERVOY can cause immune-mediated pneumonitis. The incidence of pneumonitis is higher in patients who have received prior thoracic radiation. In patients receiving OPDIVO monotherapy, immune-mediated pneumonitis occurred in 3.1% (61/1994) of patients, including Grade 4 (<0.1%), Grade 3 (0.9%), and Grade 2 (2.1%). In patients receiving OPDIVO 1 mg/kg with YERVOY 3 mg/kg every 3 weeks, immune-mediated pneumonitis occurred in 7% (31/456) of patients, including Grade 4 (0.2%), Grade 3 (2.0%), and Grade 2 (4.4%). In patients receiving OPDIVO 3 mg/kg with YERVOY 1 mg/kg every 3 weeks, immune-mediated pneumonitis occurred in 3.9% (26/666) of patients, including Grade 3 (1.4%) and Grade 2 (2.6%). In NSCLC patients receiving OPDIVO 3 mg/kg every 2 weeks with YERVOY 1 mg/kg every 6 weeks, immune-mediated pneumonitis occurred in 9% (50/576) of patients, including Grade 4 (0.5%), Grade 3 (3.5%), and Grade 2 (4.0%). Four patients (0.7%) died due to pneumonitis.

 

In Checkmate 205 and 039, pneumonitis, including interstitial lung disease, occurred in 6.0% (16/266) of patients receiving OPDIVO. Immune-mediated pneumonitis occurred in 4.9% (13/266) of patients receiving OPDIVO, including Grade 3 (n=1) and Grade 2 (n=12).

 

Immune-Mediated Colitis

 

OPDIVO and YERVOY can cause immune-mediated colitis, which may be fatal . A common symptom included in the definition of colitis was diarrhea. Cytomegalovirus (CMV) infection/reactivation has been reported in patients with corticosteroid-refractory immune-mediated colitis. In cases of corticosteroid-refractory colitis, consider repeating infectious workup to exclude alternative etiologies. In patients receiving OPDIVO monotherapy, immune-mediated colitis occurred in 2.9% (58/1994) of patients, including Grade 3 (1.7%) and Grade 2 (1%). In patients receiving OPDIVO 1 mg/kg with YERVOY 3 mg/kg every 3 weeks, immune-mediated colitis occurred in 25% (115/456) of patients, including Grade 4 (0.4%), Grade 3 (14%) and Grade 2 (8%). In patients receiving OPDIVO 3 mg/kg with YERVOY 1 mg/kg every 3 weeks, immune-mediated colitis occurred in 9% (60/666) of patients, including Grade 3 (4.4%) and Grade 2 (3.7%).

 

Immune-Mediated Hepatitis and Hepatotoxicity

 

OPDIVO and YERVOY can cause immune-mediated hepatitis. In patients receiving OPDIVO monotherapy, immune-mediated hepatitis occurred in 1.8% (35/1994) of patients, including Grade 4 (0.2%), Grade 3 (1.3%), and Grade 2 (0.4%). In patients receiving OPDIVO monotherapy in Checkmate 040, immune-mediated hepatitis requiring systemic corticosteroids occurred in 5% (8/154) of patients. In patients receiving OPDIVO 1 mg/ kg with YERVOY 3 mg/kg every 3 weeks, immune-mediated hepatitis occurred in 15% (70/456) of patients, including Grade 4 (2.4%), Grade 3 (11%), and Grade 2 (1.8%). In patients receiving OPDIVO 3 mg/kg with YERVOY 1 mg/kg every 3 weeks, immune-mediated hepatitis occurred in 7% (48/666) of patients, including Grade 4 (1.2%), Grade 3 (4.9%), and Grade 2 (0.4%).

 

OPDIVO in combination with cabozantinib can cause hepatic toxicity with higher frequencies of Grade 3 and 4 ALT and AST elevations compared to OPDIVO alone. Consider more frequent monitoring of liver enzymes as compared to when the drugs are administered as single agents. In patients receiving OPDIVO and cabozantinib, Grades 3 and 4 increased ALT or AST were seen in 11% of patients.

 

Immune-Mediated Endocrinopathies

 

OPDIVO and YERVOY can cause primary or secondary adrenal insufficiency, immune-mediated hypophysitis, immune-mediated thyroid disorders, and Type 1 diabetes mellitus, which can present with diabetic ketoacidosis. Withhold OPDIVO and YERVOY depending on severity (please see section 2 Dosage and Administration in the accompanying Full Prescribing Information). For Grade 2 or higher adrenal insufficiency, initiate symptomatic treatment, including hormone replacement as clinically indicated. Hypophysitis can present with acute symptoms associated with mass effect such as headache, photophobia, or visual field defects. Hypophysitis can cause hypopituitarism; initiate hormone replacement as clinically indicated. Thyroiditis can present with or without endocrinopathy. Hypothyroidism can follow hyperthyroidism; initiate hormone replacement or medical management as clinically indicated. Monitor patients for hyperglycemia or other signs and symptoms of diabetes; initiate treatment with insulin as clinically indicated.

 

In patients receiving OPDIVO monotherapy, adrenal insufficiency occurred in 1% (20/1994), including Grade 3 (0.4%) and Grade 2 (0.6%). In patients receiving OPDIVO 1 mg/kg with YERVOY 3 mg/kg every 3 weeks, adrenal insufficiency occurred in 8% (35/456), including Grade 4 (0.2%), Grade 3 (2.4%), and Grade 2 (4.2%). In patients receiving OPDIVO 3 mg/kg with YERVOY 1 mg/kg every 3 weeks, adrenal insufficiency occurred in 7% (48/666) of patients, including Grade 4 (0.3%), Grade 3 (2.5%), and Grade 2 (4.1%). In patients receiving OPDIVO and cabozantinib, adrenal insufficiency occurred in 4.7% (15/320) of patients, including Grade 3 (2.2%) and Grade 2 (1.9%).

 

In patients receiving OPDIVO monotherapy, hypophysitis occurred in 0.6% (12/1994) of patients, including Grade 3 (0.2%) and Grade 2 (0.3%). In patients receiving OPDIVO 1 mg/kg with YERVOY 3 mg/kg every 3 weeks, hypophysitis occurred in 9% (42/456), including Grade 3 (2.4%) and Grade 2 (6%). In patients receiving OPDIVO 3 mg/kg with YERVOY 1 mg/kg every 3 weeks, hypophysitis occurred in 4.4% (29/666) of patients, including Grade 4 (0.3%), Grade 3 (2.4%), and Grade 2 (0.9%).

 

In patients receiving OPDIVO monotherapy, thyroiditis occurred in 0.6% (12/1994) of patients, including Grade 2 (0.2%). In patients receiving OPDIVO 3 mg/kg with YERVOY 1 mg/kg every 3 weeks, thyroiditis occurred in 2.7% (22/666) of patients, including Grade 3 (4.5%) and Grade 2 (2.2%).

 

In patients receiving OPDIVO monotherapy, hyperthyroidism occurred in 2.7% (54/1994) of patients, including Grade 3 (<0.1%) and Grade 2 (1.2%). In patients receiving OPDIVO 1 mg/kg with YERVOY 3 mg/kg every 3 weeks, hyperthyroidism occurred in 9% (42/456) of patients, including Grade 3 (0.9%) and Grade 2 (4.2%). In patients receiving OPDIVO 3 mg/kg with YERVOY 1 mg/kg every 3 weeks, hyperthyroidism occurred in 12% (80/666) of patients, including Grade 3 (0.6%) and Grade 2 (4.5%).

 

In patients receiving OPDIVO monotherapy, hypothyroidism occurred in 8% (163/1994) of patients, including Grade 3 (0.2%) and Grade 2 (4.8%). In patients receiving OPDIVO 1 mg/kg with YERVOY 3 mg/kg every 3 weeks, hypothyroidism occurred in 20% (91/456) of patients, including Grade 3 (0.4%) and Grade 2 (11%). In patients receiving OPDIVO 3 mg/kg with YERVOY 1 mg/kg every 3 weeks, hypothyroidism occurred in 18% (122/666) of patients, including Grade 3 (0.6%) and Grade 2 (11%).

 

In patients receiving OPDIVO monotherapy, diabetes occurred in 0.9% (17/1994) of patients, including Grade 3 (0.4%) and Grade 2 (0.3%), and 2 cases of diabetic ketoacidosis. In patients receiving OPDIVO 3 mg/kg with YERVOY 1 mg/kg every 3 weeks, diabetes occurred in 2.7% (15/666) of patients, including Grade 4 (0.6%), Grade 3 (0.3%), and Grade 2 (0.9%).

 

Immune-Mediated Nephritis with Renal Dysfunction

 

OPDIVO and YERVOY can cause immune-mediated nephritis. In patients receiving OPDIVO monotherapy, immune-mediated nephritis and renal dysfunction occurred in 1.2% (23/1994) of patients, including Grade 4 (<0.1%), Grade 3 (0.5%), and Grade 2 (0.6%). In patients receiving OPDIVO 3 mg/kg with YERVOY 1 mg/kg every 3 weeks, immune-mediated nephritis with renal dysfunction occurred in 4.1% (27/666) of patients, including Grade 4 (0.6%), Grade 3 (1.1%), and Grade 2 (2.2%).

 

Immune-Mediated Dermatologic Adverse Reactions

 

OPDIVO can cause immune-mediated rash or dermatitis. Exfoliative dermatitis, including Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), and drug rash with eosinophilia and systemic symptoms (DRESS) has occurred with PD-1/PD-L1 blocking antibodies. Topical emollients and/or topical corticosteroids may be adequate to treat mild to moderate nonexfoliative rashes.

Contacts

Bristol Myers Squibb

Media Inquiries:
Media@BMS.com

Investors:
Tim Power

609-252-7509

timothy.power@bms.com

Nina Goworek

908-673-9711

nina.goworek@bms.com

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Categories
Healthcare Science

KEYTRUDA® (pembrolizumab) plus chemotherapy before surgery and continued as a single agent after surgery showed statistically significant event-free survival (EFS) result versus neoadjuvant chemotherapy alone in high-risk early-stage TNBC

KEYNOTE-522 Is the First Phase 3 Study With an Immunotherapy to Show Positive EFS Results in High-Risk Early-Stage Triple-Negative Breast Cancer

Merck Has Submitted These Data From KEYNOTE-522 to the US FDA for Review

 

KENILWORTH, N.J. — (BUSINESS WIRE) — $MRK #MRK–Merck (NYSE: MRK), known as MSD outside the United States and Canada, today announced positive event-free survival (EFS) data from the pivotal neoadjuvant/adjuvant Phase 3 study KEYNOTE-522. The trial investigated neoadjuvant KEYTRUDA, Merck’s anti-PD-1 therapy, plus chemotherapy followed by adjuvant KEYTRUDA as monotherapy (the KEYTRUDA regimen) compared with neoadjuvant chemotherapy followed by adjuvant placebo (the chemotherapy-placebo regimen) in patients with high-risk early-stage triple-negative breast cancer (TNBC). This is the first time an anti-PD-1/L1 therapy has demonstrated a statistically significant EFS result as combined neoadjuvant and adjuvant therapy for these patients. These results are being presented today during a European Society for Medical Oncology (ESMO) Virtual Plenary.

After a median follow-up of 39 months, the KEYTRUDA regimen reduced the risk of EFS events by 37% (HR=0.63 [95% CI, 0.48-0.82]; p=0.00031) versus the chemotherapy-placebo regimen – a statistically significant and clinically meaningful EFS result. EFS was defined as the time from randomization to the first occurrence of either disease progression that precluded definitive surgery, a local/distant recurrence, a second primary cancer, or death from any cause. As previously announced, KEYNOTE-522 met the dual primary endpoint of pathological complete response (pCR) at the first interim analysis. The trial is continuing to allow for additional follow-up of overall survival (OS), a key secondary endpoint. At this fourth interim analysis, although these data have not crossed the boundary for statistical significance, there was a 28% reduction in the risk of death with the KEYTRUDA regimen versus the chemotherapy-placebo regimen (HR=0.72 [95% CI, 0.51-1.02]; p=0.03214). The safety profile of the KEYTRUDA regimen was consistent with the known profiles of each regimen, and no new safety concerns were identified.

“Given the high rates of recurrence within the first five years of diagnosis, patients with high-risk early-stage TNBC need new treatment options,” said Dr. Peter Schmid, lead, Centre for Experimental Cancer Medicine, Barts Cancer Institute in London, England. “KEYNOTE-522 was designed to study whether the combined neoadjuvant and adjuvant regimen with KEYTRUDA could help treat the cancer earlier. Now, with more than three years of follow-up, we see the potential of this approach. These event-free survival data are very encouraging for patients and show that this combination of KEYTRUDA plus chemotherapy as neoadjuvant therapy, followed by single-agent KEYTRUDA as adjuvant therapy, may offer women with high-risk early-stage TNBC a new treatment option for this aggressive disease.”

“These highly anticipated event-free survival results in this TNBC population build upon earlier findings from the KEYNOTE-522 trial and further support the potential use of KEYTRUDA in these patients,” said Dr. Vicki Goodman, vice president, clinical research, Merck Research Laboratories. “KEYNOTE-522 is the first large randomized Phase 3 study to report a statistically significant and clinically meaningful EFS result among patients with stage II and stage III TNBC. We have submitted these data to the FDA and are working closely with the agency on its review of our application.”

KEYTRUDA is currently approved under accelerated approval in the U.S. in combination with chemotherapy for the treatment of patients with locally recurrent unresectable or metastatic TNBC whose tumors express PD-L1 (Combined Positive Score [CPS] ≥10) as determined by an FDA-approved test.

Merck is rapidly advancing a broad portfolio in women’s cancers with an extensive clinical development program for KEYTRUDA and several other investigational and approved medicines across multiple gynecologic and breast cancers. The KEYTRUDA clinical development program for TNBC encompasses several internal studies and external collaborative trials, including the ongoing studies KEYNOTE-242 and KEYNOTE-355.

Study Design and Additional Data From KEYNOTE-522

KEYNOTE-522 is a Phase 3, randomized, double-blind trial (ClinicalTrials.gov, NCT03036488). The dual primary endpoints are pCR, defined as pathological stage ypT0/Tis ypN0 at the time of definitive surgery, and EFS, defined as the time from randomization to the first occurrence of either disease progression that precluded definitive surgery, a local/distant recurrence, a second primary cancer, or death from any cause in all patients randomized. Secondary endpoints include pCR rate using alternative definitions, OS in all patients randomized, pCR rate according to all definitions, EFS and OS in patients whose tumors express PD-L1 (CPS ≥1), safety and health-related quality of life assessments. The study enrolled 1,174 patients who were randomized 2:1 to receive either:

  • The KEYTRUDA regimen: KEYTRUDA (every three weeks) plus paclitaxel (weekly) and carboplatin (weekly or every three weeks) for four cycles, followed by KEYTRUDA plus cyclophosphamide and either doxorubicin or epirubicin (every three weeks) for four cycles as neoadjuvant therapy prior to surgery, followed by nine cycles of KEYTRUDA (every three weeks) as adjuvant therapy post-surgery (n=784)
  • The chemotherapy-placebo regimen: Placebo (every three weeks) plus paclitaxel (weekly) and carboplatin (weekly or every three weeks) for four cycles, followed by placebo plus cyclophosphamide and either doxorubicin or epirubicin (every three weeks) for four cycles as neoadjuvant therapy prior to surgery, followed by nine cycles of placebo (every three weeks) as adjuvant therapy post-surgery (n=390)

As previously announced, KEYNOTE-522 met the success criterion for the dual primary endpoint of pCR at the first interim analysis; pCR was observed in 64.8% of patients treated with KEYTRUDA plus chemotherapy (n=401), an increase of 13.6% (p=0.00055) from 51.2% in patients treated with placebo plus chemotherapy (n=201). At the fourth interim analysis, KEYNOTE-522 met the success criterion for the dual primary endpoint of EFS. The study is continuing to allow for additional follow-up of OS.

At three years, 84.5% of patients treated with the KEYTRUDA regimen were alive and did not experience an EFS event compared to 76.8% of patients treated with the chemotherapy-placebo regimen.

In pre-specified exploratory subgroup analyses of EFS, the EFS benefit seen with the KEYTRUDA regimen was independent of PD-L1 expression. In the PD-L1-positive subgroup (n=973), defined as CPS ≥1, treatment with the KEYTRUDA regimen reduced the risk of EFS events by 33% (HR=0.67 [95% CI, 0.49-0.92]) versus the chemotherapy-placebo regimen. In the PD-L1-negative subgroup (n=197), defined as CPS <1, treatment with the KEYTRUDA regimen reduced the risk of EFS events by 52% (HR=0.48 [95% CI, 0.28-0.85]) versus the chemotherapy-placebo regimen.

In a pre-specified but non-randomized exploratory analysis of EFS by pCR outcome, the reduction in EFS events with the KEYTRUDA regimen was observed independent of pCR outcome at definitive surgery.

Treatment-related adverse events (TRAEs) were examined in the neoadjuvant phase, the adjuvant phase and the combined phases. TRAEs in the neoadjuvant phase have been previously reported. At the time of this data cutoff, no patients were still receiving protocol treatment. For the combined neoadjuvant and adjuvant phases, TRAEs occurred in 98.9% of patients receiving the KEYTRUDA regimen (n=783) and 99.7% of patients receiving the chemotherapy-placebo regimen (n=389); Grade 3-5 TRAEs occurred in 77.1% versus 73.3%, respectively. TRAEs led to death in 0.5% of patients receiving the KEYTRUDA regimen (n=4) and 0.3% of patients receiving the chemotherapy-placebo regimen (n=1). No new safety concerns were identified. In the adjuvant phase, TRAEs occurred in 53.7% of patients receiving adjuvant KEYTRUDA (n=588) and 48.6% of patients receiving adjuvant placebo (n=331), including 6.3% and 2.7%, respectively, who had at least one Grade ≥3 event.

Immune-mediated adverse events (AEs) and infusion reactions of any grade in the combined neoadjuvant and adjuvant phases occurred in 43.6% of patients receiving the KEYTRUDA regimen and 21.9% of patients receiving the chemotherapy-placebo regimen. The most common of these events (occurring in ≥10% of patients) were infusion reactions (18.0%) and hypothyroidism (15.1%) in patients receiving the KEYTRUDA regimen and infusion reactions (11.6%) in patients receiving the chemotherapy-placebo regimen. Immune-mediated AEs led to death in 0.3% of patients receiving the KEYTRUDA regimen (n=2) and no patients receiving the chemotherapy-placebo regimen. In the adjuvant phase, immune-mediated AEs and infusion reactions occurred in 10.2% of patients receiving adjuvant KEYTRUDA and 6.0% of patients receiving adjuvant placebo, including 2.9% and 0.3%, respectively, who had at least one Grade ≥3 event.

About Triple-Negative Breast Cancer (TNBC)

Triple-negative breast cancer is an aggressive type of breast cancer that characteristically has a high recurrence rate within the first five years after diagnosis. While some breast cancers may test positive for estrogen receptors, progesterone receptors or overexpression of human epidermal growth factor receptor 2 (HER2), TNBC tests negative for all three. Approximately 10-15% of patients with breast cancer are diagnosed with TNBC. TNBC tends to be more common in people who are younger than 40 years of age, who are African American or who have a BRCA1 mutation.

About KEYTRUDA® (pembrolizumab) Injection, 100 mg

KEYTRUDA is an anti-programmed death receptor-1 (PD-1) therapy that works by increasing the ability of the body’s immune system to help detect and fight tumor cells. KEYTRUDA is a humanized monoclonal antibody that blocks the interaction between PD-1 and its ligands, PD-L1 and PD-L2, thereby activating T lymphocytes which may affect both tumor cells and healthy cells.

Merck has the industry’s largest immuno-oncology clinical research program. There are currently more than 1,500 trials studying KEYTRUDA across a wide variety of cancers and treatment settings. The KEYTRUDA clinical program seeks to understand the role of KEYTRUDA across cancers and the factors that may predict a patient’s likelihood of benefitting from treatment with KEYTRUDA, including exploring several different biomarkers.

Selected KEYTRUDA® (pembrolizumab) Indications in the U.S.

Melanoma

KEYTRUDA is indicated for the treatment of patients with unresectable or metastatic melanoma.

KEYTRUDA is indicated for the adjuvant treatment of patients with melanoma with involvement of lymph node(s) following complete resection.

Non-Small Cell Lung Cancer

KEYTRUDA, in combination with pemetrexed and platinum chemotherapy, is indicated for the first-line treatment of patients with metastatic nonsquamous non-small cell lung cancer (NSCLC), with no EGFR or ALK genomic tumor aberrations.

KEYTRUDA, in combination with carboplatin and either paclitaxel or paclitaxel protein-bound, is indicated for the first-line treatment of patients with metastatic squamous NSCLC.

KEYTRUDA, as a single agent, is indicated for the first-line treatment of patients with NSCLC expressing PD-L1 [tumor proportion score (TPS) ≥1%] as determined by an FDA-approved test, with no EGFR or ALK genomic tumor aberrations, and is:

  • stage III where patients are not candidates for surgical resection or definitive chemoradiation, or
  • metastatic.

KEYTRUDA, as a single agent, is indicated for the treatment of patients with metastatic NSCLC whose tumors express PD-L1 (TPS ≥1%) as determined by an FDA-approved test, with disease progression on or after platinum-containing chemotherapy. Patients with EGFR or ALK genomic tumor aberrations should have disease progression on FDA-approved therapy for these aberrations prior to receiving KEYTRUDA.

Head and Neck Squamous Cell Cancer

KEYTRUDA, in combination with platinum and fluorouracil (FU), is indicated for the first-line treatment of patients with metastatic or with unresectable, recurrent head and neck squamous cell carcinoma (HNSCC).

KEYTRUDA, as a single agent, is indicated for the first-line treatment of patients with metastatic or with unresectable, recurrent HNSCC whose tumors express PD-L1 (CPS ≥1) as determined by an FDA-approved test.

KEYTRUDA, as a single agent, is indicated for the treatment of patients with recurrent or metastatic HNSCC with disease progression on or after platinum-containing chemotherapy.

Classical Hodgkin Lymphoma

KEYTRUDA is indicated for the treatment of adult patients with relapsed or refractory classical Hodgkin lymphoma (cHL).

KEYTRUDA is indicated for the treatment of pediatric patients with refractory cHL, or cHL that has relapsed after 2 or more lines of therapy.

Primary Mediastinal Large B-Cell Lymphoma

KEYTRUDA is indicated for the treatment of adult and pediatric patients with refractory primary mediastinal large B-cell lymphoma (PMBCL), or who have relapsed after 2 or more prior lines of therapy. KEYTRUDA is not recommended for treatment of patients with PMBCL who require urgent cytoreductive therapy.

Urothelial Carcinoma

KEYTRUDA is indicated for the treatment of patients with locally advanced or metastatic urothelial carcinoma (mUC) who are not eligible for cisplatin-containing chemotherapy and whose tumors express PD-L1 (CPS ≥10) as determined by an FDA-approved test, or in patients who are not eligible for any platinum-containing chemotherapy regardless of PD-L1 status. This indication is approved under accelerated approval based on tumor response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.

KEYTRUDA is indicated for the treatment of patients with locally advanced or mUC who have disease progression during or following platinum-containing chemotherapy or within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy.

KEYTRUDA is indicated for the treatment of patients with Bacillus Calmette-Guerin-unresponsive, high-risk, non-muscle invasive bladder cancer (NMIBC) with carcinoma in situ with or without papillary tumors who are ineligible for or have elected not to undergo cystectomy.

Microsatellite Instability-High or Mismatch Repair Deficient Cancer

KEYTRUDA is indicated for the treatment of adult and pediatric patients with unresectable or metastatic microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) solid tumors that have progressed following prior treatment and who have no satisfactory alternative treatment options.

This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials. The safety and effectiveness of KEYTRUDA in pediatric patients with MSI-H central nervous system cancers have not been established.

Microsatellite Instability-High or Mismatch Repair Deficient Colorectal Cancer

KEYTRUDA is indicated for the treatment of patients with unresectable or metastatic MSI-H or dMMR colorectal cancer (CRC).

Gastric Cancer

KEYTRUDA, in combination with trastuzumab, fluoropyrimidine- and platinum-containing chemotherapy, is indicated for the first-line treatment of patients with locally advanced unresectable or metastatic HER2-positive gastric or gastroesophageal junction (GEJ) adenocarcinoma. This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.

Esophageal Cancer

KEYTRUDA is indicated for the treatment of patients with locally advanced or metastatic esophageal or GEJ (tumors with epicenter 1 to 5 centimeters above the GEJ) carcinoma that is not amenable to surgical resection or definitive chemoradiation either:

  • in combination with platinum- and fluoropyrimidine-based chemotherapy, or
  • as a single agent after one or more prior lines of systemic therapy for patients with tumors of squamous cell histology that express PD-L1 (CPS ≥10) as determined by an FDA-approved test.

Cervical Cancer

KEYTRUDA is indicated for the treatment of patients with recurrent or metastatic cervical cancer with disease progression on or after chemotherapy whose tumors express PD-L1 (CPS ≥1) as determined by an FDA-approved test. This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.

Hepatocellular Carcinoma

KEYTRUDA is indicated for the treatment of patients with hepatocellular carcinoma (HCC) who have been previously treated with sorafenib. This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.

Merkel Cell Carcinoma

KEYTRUDA is indicated for the treatment of adult and pediatric patients with recurrent locally advanced or metastatic Merkel cell carcinoma (MCC). This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.

Renal Cell Carcinoma

KEYTRUDA, in combination with axitinib, is indicated for the first-line treatment of patients with advanced renal cell carcinoma.

Tumor Mutational Burden-High Cancer

KEYTRUDA is indicated for the treatment of adult and pediatric patients with unresectable or metastatic tumor mutational burden-high (TMB-H) [≥10 mutations/megabase] solid tumors, as determined by an FDA-approved test, that have progressed following prior treatment and who have no satisfactory alternative treatment options. This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials. The safety and effectiveness of KEYTRUDA in pediatric patients with TMB-H central nervous system cancers have not been established.

Cutaneous Squamous Cell Carcinoma

KEYTRUDA is indicated for the treatment of patients with recurrent or metastatic cutaneous squamous cell carcinoma (cSCC) or locally advanced cSCC that is not curable by surgery or radiation.

Triple-Negative Breast Cancer

KEYTRUDA, in combination with chemotherapy, is indicated for the treatment of patients with locally recurrent unresectable or metastatic triple-negative breast cancer (TNBC) whose tumors express PD-L1 (CPS ≥10) as determined by an FDA-approved test. This indication is approved under accelerated approval based on progression-free survival. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.

Selected Important Safety Information for KEYTRUDA

Severe and Fatal Immune-Mediated Adverse Reactions

KEYTRUDA is a monoclonal antibody that belongs to a class of drugs that bind to either the programmed death receptor-1 (PD-1) or the programmed death ligand 1 (PD-L1), blocking the PD-1/PD-L1 pathway, thereby removing inhibition of the immune response, potentially breaking peripheral tolerance and inducing immune-mediated adverse reactions. Immune-mediated adverse reactions, which may be severe or fatal, can occur in any organ system or tissue, can affect more than one body system simultaneously, and can occur at any time after starting treatment or after discontinuation of treatment. Important immune-mediated adverse reactions listed here may not include all possible severe and fatal immune-mediated adverse reactions.

Monitor patients closely for symptoms and signs that may be clinical manifestations of underlying immune-mediated adverse reactions. Early identification and management are essential to ensure safe use of anti–PD-1/PD-L1 treatments. Evaluate liver enzymes, creatinine, and thyroid function at baseline and periodically during treatment. In cases of suspected immune-mediated adverse reactions, initiate appropriate workup to exclude alternative etiologies, including infection. Institute medical management promptly, including specialty consultation as appropriate.

Withhold or permanently discontinue KEYTRUDA depending on severity of the immune-mediated adverse reaction. In general, if KEYTRUDA requires interruption or discontinuation, administer systemic corticosteroid therapy (1 to 2 mg/kg/day prednisone or equivalent) until improvement to Grade 1 or less. Upon improvement to Grade 1 or less, initiate corticosteroid taper and continue to taper over at least 1 month. Consider administration of other systemic immunosuppressants in patients whose adverse reactions are not controlled with corticosteroid therapy.

Immune-Mediated Pneumonitis

KEYTRUDA can cause immune-mediated pneumonitis. The incidence is higher in patients who have received prior thoracic radiation. Immune-mediated pneumonitis occurred in 3.4% (94/2799) of patients receiving KEYTRUDA, including fatal (0.1%), Grade 4 (0.3%), Grade 3 (0.9%), and Grade 2 (1.3%) reactions. Systemic corticosteroids were required in 67% (63/94) of patients. Pneumonitis led to permanent discontinuation of KEYTRUDA in 1.3% (36) and withholding in 0.9% (26) of patients. All patients who were withheld reinitiated KEYTRUDA after symptom improvement; of these, 23% had recurrence. Pneumonitis resolved in 59% of the 94 patients.

Pneumonitis occurred in 8% (31/389) of adult patients with cHL receiving KEYTRUDA as a single agent, including Grades 3-4 in 2.3% of patients. Patients received high-dose corticosteroids for a median duration of 10 days (range: 2 days to 53 months). Pneumonitis rates were similar in patients with and without prior thoracic radiation. Pneumonitis led to discontinuation of KEYTRUDA in 5.4% (21) of patients. Of the patients who developed pneumonitis, 42% interrupted KEYTRUDA, 68% discontinued KEYTRUDA, and 77% had resolution.

Immune-Mediated Colitis

KEYTRUDA can cause immune-mediated colitis, which may present with diarrhea. Cytomegalovirus infection/reactivation has been reported in patients with corticosteroid-refractory immune-mediated colitis. In cases of corticosteroid-refractory colitis, consider repeating infectious workup to exclude alternative etiologies. Immune-mediated colitis occurred in 1.7% (48/2799) of patients receiving KEYTRUDA, including Grade 4 (<0.1%), Grade 3 (1.1%), and Grade 2 (0.4%) reactions. Systemic corticosteroids were required in 69% (33/48); additional immunosuppressant therapy was required in 4.

Contacts

Media:

Melissa Moody

(215) 407-3536

Ayn Wisler

(908) 740-5590

Investors:

Peter Dannenbaum

(908) 740-1037

Courtney Ronaldo

(908) 740-6132

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Categories
Business

AM Best maintains under review with negative implications status for credit ratings of American Millennium Insurance Company and Citadel Reinsurance Company Limited

OLDWICK, N.J. — (BUSINESS WIRE) — #insurance—AM Best has maintained the under review with negative implications status for the Financial Strength Rating (FSR) of C- (Weak) and the Long-Term Issuer Credit Rating (Long-Term ICR) of “cc” (Weak) of American Millennium Insurance Company (AMIC) (Bridgewater, NJ), a wholly owned subsidiary of Citadel Reinsurance Company Limited (Citadel Re) (Hamilton, Bermuda). Additionally, AM Best has maintained the under review with negative implications status for the FSR of B (Fair) and the Long-Term ICR of “bb” (Fair) of Citadel Re.

AM Best downgraded the Credit Ratings (ratings) of AMIC and Citadel Re in February 2021 and maintained the under review with negative implications status following the downgrade of the ratings of AMIC in October 2020. These rating actions resulted from persistent net underwriting losses that continued into the second half of 2020 and negatively impacted the risk-adjusted capitalization of AMIC and Citadel Re given its direct ownership of AMIC. For AMIC, the impact of these unanticipated losses (net of reinsurance) resulted in a significant deterioration in surplus and notably, risk-based capital (RBC) levels, which were likely to prompt state regulatory actions. The “under review” status was pending the parent Citadel Re potentially recapitalizing AMIC’s balance sheet and its plans to raise more capital from outside investors. The negative implications for AMIC considered the pending regulatory pressures and the uncertainty related to AMIC as a going concern.

 

As of late June, 2021, AMIC’s regulator, the Department of Banking and Insurance (DOBI) of New Jersey, had agreed that Citadel Re will immediately recapitalize AMIC with $2.55 million in the first tranche, to correct the RBC to 200% or above, based upon the first quarter 2021 financial statements. The first tranche of the recapitalization has now been completed. DOBI expects another cash contribution of $3.65 million before the end of July (to push the RBC above 300%), following the schedules of Citadel Re’s fundraising.

 

AM Best is maintaining the under review with negative implications status for both AMIC and Citadel Re. Although some of the uncertainties incorporated in the previous under review status had been addressed through the completion of the first tranche of recapitalization, the planned external fundraising has not yet been completed and is likely to be delayed until August. Although Citadel Re reported a fair amount of interest from potential investors, the ultimate success of these efforts is far from certain. If the external fundraising is ultimately unsuccessful, AM Best expects continuing pressure from AMIC’s regulator (DOBI) while Citadel Re’s ratings could also be negatively impacted. AM Best plans to finalize the under review status of both Citadel Re and AMIC once the external funding is completed, which is expected to occur sometime in the third quarter of 2021.

 

This press release relates to Credit Ratings that have been published on AM Best’s website. For all rating information relating to the release and pertinent disclosures, including details of the office responsible for issuing each of the individual ratings referenced in this release, please see AM Best’s Recent Rating Activity web page. For additional information regarding the use and limitations of Credit Rating opinions, please view Guide to Best’s Credit Ratings. For information on the proper use of Best’s Credit Ratings, Best’s Preliminary Credit Assessments and AM Best press releases, please view Guide to Proper Use of Best’s Ratings & Assessments.

 

AM Best is a global credit rating agency, news publisher and data analytics provider specializing in the insurance industry. Headquartered in the United States, the company does business in over 100 countries with regional offices in London, Amsterdam, Dubai, Hong Kong, Singapore and Mexico City. For more information, visit www.ambest.com.

 

Copyright © 2021 by A.M. Best Rating Services, Inc. and/or its affiliates. ALL RIGHTS RESERVED.

Contacts

Jieqiu Fan
Senior Financial Analyst
+1 908 439 2200, ext. 5372
jieqiu.fan@ambest.com

Christopher Sharkey
Manager, Public Relations
+1 908 439 2200, ext. 5159
christopher.sharkey@ambest.com

Daniel Ryan
Senior Director
+1 908 439 2200, ext. 5325
daniel.ryan@ambest.com

Jim Peavy
Director, Communications
+1 908 439 2200, ext. 5644
james.peavy@ambest.com

Categories
Business

AM Best affirms credit ratings of Brookfield Annuity Company

OLDWICK, N.J. — (BUSINESS WIRE) — #insurance—AM Best has affirmed the Financial Strength Rating of A- (Excellent) and the Long-Term Issuer Credit Rating of “a-” (Excellent) of Brookfield Annuity Company (Toronto, Ontario, Canada). Brookfield Annuity Company is a wholly owned subsidiary of Brookfield Asset Management Reinsurance Partners Ltd (BAM Re) [TSX: BAMR; NYSE: BAMR]. The outlook of these Credit Ratings (ratings) is stable.

The ratings reflect Brookfield Annuity Company’s balance sheet strength, which AM Best assesses as strong, as well as its adequate operating performance, neutral business profile and appropriate enterprise risk management.

 

The ratings also reflect the company’s ability to execute on its business plan and the utilization of the balance sheet. The business profile of the company has improved as the company matures.

 

The balance sheet strength is assessed based on the company’s five-year business plan, with a very high level of capital injected into the business at startup by the parent company. As typically seen with startups, risk-adjusted capital has decreased over the years as Brookfield Annuity Company writes business. As of year-end 2020, the parent company has contributed a total of $100 million of capital. AM Best expects the company’s balance sheet capacity to remain stable going forward as the in-force business emerges. Furthermore, the company has developed a good reinsurance program that serves to strengthen capital management. Brookfield Annuity Company is a pension-risk transfer (PRT) carrier in the Canada market, and it continues to write profitable business.

 

The company has achieved a respectable market share in the PRT market and has expanded its product offering. The company continues to nurture its developed enterprise risk management program.

 

This press release relates to Credit Ratings that have been published on AM Best’s website. For all rating information relating to the release and pertinent disclosures, including details of the office responsible for issuing each of the individual ratings referenced in this release, please see AM Best’s Recent Rating Activity web page. For additional information regarding the use and limitations of Credit Rating opinions, please view Guide to Best’s Credit Ratings. For information on the proper media use of Best’s Credit Ratings and AM Best press releases, please view Guide for Media – Proper Use of Best’s Credit Ratings and AM Best Rating Action Press Releases.

 

AM Best is a global credit rating agency, news publisher and data analytics provider specializing in the insurance industry. Headquartered in the United States, the company does business in over 100 countries with regional offices in London, Amsterdam, Dubai, Hong Kong, Singapore and Mexico City. For more information, visit www.ambest.com.

Copyright © 2021 by A.M. Best Rating Services, Inc. and/or its affiliates. ALL RIGHTS RESERVED.

Contacts

Bruno Caron
Associate Director
+1 908 439 2200, ext. 5144
bruno.caron@ambest.com

Anthony McSwieney
Senior Financial Analyst
+1 908 439 2200, ext. 5715
anthony.mcswieney@ambest.com

Christopher Sharkey
Manager, Public Relations
+1 908 439 2200, ext. 5159
christopher.sharkey@ambest.com

Jim Peavy
Director, Communications
+1 908 439 2200, ext. 5644
james.peavy@ambest.com