Tag: Trial

Categories
For Edit

Analysis: Trump’s Senate trial matters regardless of outcome

FILE – In this Jan. 6, 2021, file photo, President Donald Trump arrives to speak at a rally in Washington. Arguments begin Tuesday, Feb. 9, in the impeachment trial of Donald Trump on allegations that he incited the violent mob that stormed the U.S. Capitol on Jan. 6. (AP Photo/Jacquelyn Martin, File)

 

WASHINGTON (AP) — This matters.

The outcome may seem preordained in the unprecedented second impeachment trial of Donald Trump.

Democrats prosecuting the former president for inciting a deadly insurrection at the U.S. Capitol will struggle to persuade at least 17 Republicans to convict Trump and bar him from office. Forty-five of the 50 Republican senators backed a bid last month to dismiss the trial, essentially telegraphing how the final vote will play out.

But the trial set to begin Tuesday is ultimately a test of whether a president, holding an office that many of the nation’s founders feared could become too powerful in the wrong hands, is above the law. Senators will be forced to sit still, listen to evidence and wrestle with elemental questions about American democracy. There will be visual, visceral evidence, and the American people will also be sitting in their own form of judgment as they watch.

The verdict and the process itself will be scrutinized for generations.

“For historians, what that trial does is to provide additional evidence and documentation under oath,” said Carol Anderson, a professor of African American studies at Emory University. “It also gives us a sense of the strength, or the weakness, in American democracy as the senators are confronted with this evidence.”

That record is certain to be grisly, a reminder on a human level of the horror at the Capitol on Jan. 6.

Senators will review Trump’s call that morning to “fight like hell” before the mob of loyalists showed up to Capitol Hill to do just that. Senators will be reminded of the rioters’ chants calling for then-Vice President Mike Pence’s hanging. House prosecutors could resurface the image of a police officer crushed between doors, blood trickling from his mouth, as the violent crowd moved in. There might be additional evidence of how another officer, Brian Sicknick, died defending the building.

If that’s not enough, senators will be reminded of their own vulnerability as they fled the mob entering their chamber — one of the most rarefied spaces in Washington — in fear of their lives.

And then they’ll have to decide whether there should be consequences. But the potential of an acquittal doesn’t mean the trial should be abandoned before it begins, said Rep. Val Demings, who was an impeachment manager in Trump’s first trial.

“The jury not convicting is always a possibility,” the Florida Democrat said, recalling her previous career as the chief of the Orlando Police Department. “But decisions are never made solely on that.”

Nearly two-thirds of Americans believe Trump bears at least a moderate amount of responsibility for the riot, according to a poll released last week by The Associated Press-NORC Center for Public Affairs Research. That includes half who say Trump bears a great deal or quite a bit of responsibility.

Most Republicans absolve him of guilt, but about 3 in 10 think he bears at least a measure of blame for the events.

Of course, Congress has more on its plate than another fight over the previous president. In the early days of his administration, President Joe Biden is pushing a $1.9 trillion package to confront the coronavirus pandemic. He’s also pressing lawmakers on immigration, health care and climate change.

Lee Hamilton, a former Democratic congressman from Indiana who served during President Bill Clinton’s impeachment, said a trial could be a “distraction” from larger priorities. He suggested censure could be a better use of time and that the historical record could be achieved through the creation of a commission like the one he helped lead to investigate the terrorist attacks of Sept. 11, 2001.

But, he said, that only works if Congress is united on the need for a thorough investigation of what happened during the insurrection and provides the resources to back it up.

“If you’re going to do it, do it right,” Hamilton said.

As much as the trial is about history, the implications are just as powerful in the present moment. Leaders in capitals across the world are watching what happens in Washington to assess whether the U.S. remains committed to democratic principles. Steadfast American allies, including Germany and the United Kingdom, expressed shock at the insurrection.

U.S. foes seized on the violence to say that the United States could not now lecture others on the sanctity of democracy.

“American democracy is obviously limping on both feet,” Konstantin Kosachev, head of the foreign affairs committee in Russia’s upper house of parliament, said after the riot. “America no longer charts a course and therefore has lost all rights to set it — and even more so to impose it on others.”

It’s telling that Republicans aren’t going into the trial with a robust defense of Trump. Few are publicly defending his behavior in the runup to the insurrection, whether it’s his baseless insistence that the election was “stolen” or his more specific — and troubling — calls to supporters to rally on his behalf.

Instead, the GOP is narrowly focused on a more technical constitutional issue, arguing that a president can’t face an impeachment trial once out of office, a path they believe is easier to defend than trying to rationalize Trump’s actions.

Anticipating that posture, Democrats filed a pretrial brief noting there’s no “January exception” in the Constitution.

“Presidents do not get a free pass to commit high crimes and misdemeanors near the end of their term,” the House impeachment managers wrote.

The trial comes as the GOP is struggling with its future.

Sen. Mitch McConnell of Kentucky, the Republican leader, has flirted with the possibility of purging Trump from the party. If Trump is convicted, the Senate could vote to bar him from seeking office again, a notable punishment for someone who has dangled the potential of a 2024 presidential run to keep bending the party to his will.

McConnell hasn’t yet said how he’ll vote, and, so far, only a few moderate Republicans seem certain to convict. They’re running into the reality that Trump’s supporters remain a dominant force in the party.

The trial “really will only reinforce what we already know about American politics,” said Brendan Buck, a top adviser to former House Speaker Paul Ryan, R-Wis. ”And in that, I mean we are so tribal and divided that there’s really no question where people will fall down on something that should generate thoughtful discourse and reflection about a fundamental democratic principle.”

___

EDITOR’S NOTE — Political Editor Steven Sloan has covered politics for The Associated Press since 2018. Follow him at http://twitter.com/stevenpsloan

 

— Associated Press

Categories
For Edit

Impeachment managers call Trump ‘singularly responsible’ for riot

Filings due today from the House impeachment managers and former President Donald J. Trump’s lawyers will outline their cases ahead of his trial next week. Meanwhile, President Biden will sign executive orders on immigration.

 

— NYT: Top Stories

Categories
Healthcare

Opdivo® (nivolumab) in combination with CABOMETYX® (cabozantinib) demonstrates significant survival benefits in patients with advanced Renal Cell Carcinoma in pivotal Phase 3 CheckMate -9ER trial

Opdivo in combination with CABOMETYX showed superior overall survival and doubled median progression-free survival and objective response rate with a favorable safety profile vs. sunitinib

Efficacy benefits were observed across key patient subgroups, including all International Metastatic Renal Cell Carcinoma Database Consortium risk and PD-L1 subgroups

Data selected for presentation during a Presidential Symposium and featured in official Press Programme at European Society for Medical Oncology Virtual Congress 2020

PRINCETON, N.J., & ALAMEDA, Calif.–(BUSINESS WIRE)–$BMY #BMS—Bristol Myers Squibb (NYSE: BMY) and Exelixis, Inc. (NASDAQ: EXEL) today announced the first presentation of results from the pivotal Phase 3 CheckMate -9ER trial, in which Opdivo® (nivolumab) in combination with CABOMETYX® (cabozantinib) demonstrated significant improvements across all efficacy endpoints, including overall survival (OS), in previously untreated advanced renal cell carcinoma (RCC). Opdivo in combination with CABOMETYX reduced the risk of death by 40% vs. sunitinib (Hazard Ratio [HR] 0.60; 98.89% Confidence Interval [CI]: 0.40 to 0.89; p=0.0010; median OS not reached in either arm). In patients receiving Opdivo in combination with CABOMETYX, median progression-free survival (PFS), the trial’s primary endpoint, was doubled compared to those receiving sunitinib alone: 16.6 months vs. 8.3 months, respectively (HR 0.51; 95% CI: 0.41 to 0.64; p<0.0001).

In addition, Opdivo in combination with CABOMETYX demonstrated a superior objective response rate (ORR), with twice as many patients responding compared to sunitinib (56% vs. 27%), and 8% vs. 5% achieved a complete response. Opdivo in combination with CABOMETYX was associated with a longer duration of response than sunitinib, with a median duration of 20.2 months vs. 11.5 months. All of these key efficacy results were consistent across the pre-specified International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) risk and PD-L1 subgroups.

Opdivo combined with CABOMETYX was well tolerated and reflected the known safety profiles of the immunotherapy and tyrosine kinase inhibitor (TKI) components in previously untreated advanced RCC. The incidence of treatment-related adverse events (TRAEs), including any-grade and high-grade TRAEs, was slightly higher for Opdivo in combination with CABOMETYX vs. sunitinib (97% vs. 93% for any-grade; 61% vs. 51% for grade 3 and higher), with a low rate of treatment-related discontinuations (6% for Opdivo only, 7% for CABOMETYX only and 3% for both Opdivo and CABOMETYX vs. 9% for sunitinib). Patients treated with Opdivo in combination with CABOMETYX reported significantly better health-related quality of life than those treated with sunitinib at most time points, according to National Comprehensive Cancer Network-Functional Assessment of Cancer Therapy (NCCN-FACT) Kidney Symptom Index 19 (FKSI-19) scores.

These results (Presentation #696O_PR) will be featured as a Proffered Paper during a Presidential Symposium at the European Society for Medical Oncology (ESMO) Virtual Congress 2020, on September 19, 2020 from 19:34-19:46 CEST.

“While we’ve seen considerable progress in the treatment of metastatic renal cell carcinoma, we must continue to research new options to help more patients achieve positive outcomes,” said Dr. Toni Choueiri, Director of the Lank Center for Genitourinary Oncology at Dana-Farber Cancer Institute and Jerome and Nancy Kohlberg Professor of Medicine at Harvard Medical School. “The CheckMate -9ER data demonstrate meaningful efficacy benefits with nivolumab plus cabozantinib, which significantly improved overall survival and doubled progression-free survival and objective response rate with consistent effects observed across pre-specified subgroups. These results, along with a favorable tolerability profile and superior health-related quality of life, highlight this regimen’s potential importance among combinations of immunotherapies and tyrosine kinase inhibitors.”

Based on these efficacy and safety results from CheckMate -9ER, Bristol Myers Squibb and Exelixis’ partner Ipsen, which has exclusive rights to commercialize and develop CABOMETYX outside of the U.S. and Japan, each submitted type II variation applications for Opdivo plus CABOMETYX to the European Medicines Agency (EMA). On September 12, the EMA validated the type II variations, confirming the submissions are complete and beginning the EMA’s centralized review process. In addition, Bristol Myers Squibb and Exelixis recently completed their respective U.S. Food and Drug Administration (FDA) submissions for Opdivo in combination with CABOMETYX and, along with their partners, plan to discuss the CheckMate -9ER data with regulatory authorities across the world.

“These data are yet another example of the potential of immunotherapy-based combinations to meaningfully extend survival for patients with advanced cancers, strengthening our legacy in the genitourinary space,” said Nick Botwood, M.D., vice president, interim head, Oncology Development, Bristol Myers Squibb. “Opdivo was the first immune checkpoint inhibitor approved as a second-line treatment for advanced renal cell carcinoma, and then, with the addition of Yervoy, the first dual immunotherapy approved for certain patients in the first-line setting. With the promising results from CheckMate -9ER, we hope to bring the highly efficacious combination of Opdivo and CABOMETYX to patients with advanced renal cell carcinoma for whom an immunotherapy plus tyrosine kinase inhibitor regimen is chosen.”

“Considering the scientific and clinical evidence suggesting CABOMETYX uniquely creates a more immune-permissive tumor environment that may allow for synergistic antitumor activity when combined with Opdivo, we’re encouraged by the significant and consistent efficacy benefits shown in Checkmate -9ER for the first-line treatment of advanced kidney cancer, including all IMDC risk groups and PD-L1 status,” said Gisela Schwab, M.D., president, product development and medical affairs and chief medical officer, Exelixis. “The favorable efficacy and tolerability profile suggests that, if approved, CABOMETYX in combination with Opdivo would be an important new option for patients with advanced kidney cancer.”

Bristol Myers Squibb and Exelixis thank the patients and investigators who were involved in the CheckMate -9ER clinical trial.

About CheckMate -9ER

CheckMate -9ER is an open-label, randomized, multi-national Phase 3 trial evaluating patients with previously untreated advanced or metastatic renal cell carcinoma (RCC). A total of 651 patients (23% favorable risk, 58% intermediate risk, 20% poor risk; 25% PD-L1≥1%) were randomized to Opdivo plus CABOMETYX (n=323) vs. sunitinib (n=328). The primary endpoint is progression-free survival (PFS). Secondary endpoints include overall survival (OS) and objective response rate (ORR). The primary efficacy analysis is comparing the doublet combination vs. sunitinib in all randomized patients. The trial is sponsored by Bristol Myers Squibb and Ono Pharmaceutical Co and co-funded by Exelixis, Ipsen and Takeda Pharmaceutical Company Limited.

About Renal Cell Carcinoma

Renal cell carcinoma (RCC) is the most common type of kidney cancer in adults, accounting for more than 140,000 deaths worldwide each year. RCC is approximately twice as common in men as in women, with the highest rates of the disease in North America and Europe. Globally, the five-year survival rate for those diagnosed with metastatic, or advanced, kidney cancer is 12.1%.

Bristol Myers Squibb: Advancing Cancer Research

At Bristol Myers Squibb, patients are at the center of everything we do. The goal of our cancer research is to increase patients’ quality of life, long-term survival and make cure a possibility. We harness our deep scientific experience, cutting-edge technologies and discovery platforms to discover, develop and deliver novel treatments for patients.

Building upon our transformative work and legacy in hematology and Immuno-Oncology that has changed survival expectations for many cancers, our researchers are advancing a deep and diverse pipeline across multiple modalities. In the field of immune cell therapy, this includes registrational CAR T cell agents for numerous diseases, and a growing early-stage pipeline that expands cell and gene therapy targets, and technologies. We are developing cancer treatments directed at key biological pathways using our protein homeostasis platform, a research capability that has been the basis of our approved therapies for multiple myeloma and several promising compounds in early- to mid-stage development. Our scientists are targeting different immune system pathways to address interactions between tumors, the microenvironment and the immune system to further expand upon the progress we have made and help more patients respond to treatment. Combining these approaches is key to delivering potential new options for the treatment of cancer and addressing the growing issue of resistance to immunotherapy. We source innovation internally, and in collaboration with academia, government, advocacy groups and biotechnology companies, to help make the promise of transformational medicines a reality for patients.

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 CABOMETYX®

In the U.S., CABOMETYX tablets are approved for the treatment of patients with advanced RCC and for the treatment of patients with HCC who have been previously treated with sorafenib. CABOMETYX tablets have also received regulatory approvals in the European Union, Japan and additional countries and regions worldwide. In 2016, Exelixis granted Ipsen exclusive rights for the commercialization and further clinical development of cabozantinib outside of the United States and Japan. In 2017, Exelixis granted exclusive rights to Takeda Pharmaceutical Company Limited for the commercialization and further clinical development of cabozantinib for all future indications in Japan. Exelixis holds the exclusive rights to develop and commercialize cabozantinib in the United States.

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) is indicated for the treatment of patients with metastatic small cell lung cancer (SCLC) with progression after platinum-based chemotherapy and at least one other line of therapy. 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 advanced renal cell carcinoma (RCC) who have received prior anti-angiogenic therapy.

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

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.

IMPORTANT SAFETY INFORMATION

Severe and Fatal Immune-Mediated Adverse Reactions

Immune-mediated adverse reactions listed herein may not be inclusive of 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 at any time after starting or discontinuing YERVOY. Early identification and management are essential to ensure safe use of 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 before each dose. Institute medical management promptly, including specialty consultation as appropriate.

Withhold or permanently discontinue YERVOY depending on severity. In general, if YERVOY requires interruption or discontinuation, administer systemic corticosteroid therapy (1 to 2 mg/kg/day prednisone or equivalent) until improvement to Grade 1 or less followed by corticosteroid taper for at least 1 month. Consider administration of other systemic immunosuppressants in patients whose immune-mediated adverse reaction is not controlled with corticosteroid therapy. Institute hormone replacement therapy for endocrinopathies as warranted.

Immune-Mediated Pneumonitis

OPDIVO can cause immune-mediated pneumonitis. Fatal cases have been reported. Monitor patients for signs with radiographic imaging and for symptoms of pneumonitis. Administer corticosteroids for Grade 2 or more severe pneumonitis. Permanently discontinue for Grade 3 or 4 and withhold until resolution for Grade 2. In patients receiving OPDIVO monotherapy, fatal cases of immune-mediated pneumonitis have occurred. Immune-mediated pneumonitis occurred in 3.1% (61/1994) of patients. In melanoma patients receiving OPDIVO 1 mg/kg with YERVOY 3 mg/kg, immune-mediated pneumonitis occurred in 6% (25/407) of patients. In HCC patients receiving OPDIVO 1 mg/kg with YERVOY 3 mg/kg, immune-mediated pneumonitis occurred in 10% (5/49) of patients. In RCC patients receiving OPDIVO 3 mg/kg with YERVOY 1 mg/kg, immune-mediated pneumonitis occurred in 4.4% (24/547) of patients. In MSI-H/dMMR mCRC patients receiving OPDIVO 3 mg/kg with YERVOY 1 mg/kg, immune-mediated pneumonitis occurred in 1.7% (2/119) of patients. In NSCLC patients receiving OPDIVO 3 mg/kg with YERVOY 1 mg/kg, immune-mediated pneumonitis occurred in 9% (50/576) of patients, including Grade 4 (0.5%), Grade 3 (3.5%), and Grade 2 (4.0%) immune-mediated pneumonitis. Four patients (0.7%) died due to pneumonitis. The incidence and severity of immune-mediated pneumonitis in patients with NSCLC treated with OPDIVO 360 mg every 3 weeks in combination with YERVOY 1 mg/kg every 6 weeks and 2 cycles of platinum-doublet chemotherapy were comparable to treatment with OPDIVO in combination with YERVOY only.

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: Grade 3 (n=1) and Grade 2 (n=12).

Immune-Mediated Colitis

OPDIVO can cause immune-mediated colitis. Monitor patients for signs and symptoms of colitis. Administer corticosteroids for Grade 2 (of more than 5 days duration), 3, or 4 colitis. Withhold OPDIVO monotherapy for Grade 2 or 3 and permanently discontinue for Grade 4 or recurrent colitis upon re-initiation of OPDIVO. When administered with YERVOY, withhold OPDIVO and YERVOY for Grade 2 and permanently discontinue for Grade 3 or 4 or recurrent colitis. In patients receiving OPDIVO monotherapy, immune-mediated colitis occurred in 2.9% (58/1994) of patients. In melanoma patients receiving OPDIVO 1 mg/kg with YERVOY 3 mg/kg, immune-mediated colitis occurred in 26% (107/407) of patients including three fatal cases. In HCC patients receiving OPDIVO 1 mg/kg with YERVOY 3 mg/kg, immune-mediated colitis occurred in 10% (5/49) of patients. In RCC patients receiving OPDIVO 3 mg/kg with YERVOY 1 mg/kg, immune-mediated colitis occurred in 10% (52/547) of patients. In MSI-H/dMMR mCRC patients receiving OPDIVO 3 mg/kg with YERVOY 1 mg/kg, immune-mediated colitis occurred in 7% (8/119) of patients.

In a separate Phase 3 trial of YERVOY 3 mg/kg, immune-mediated diarrhea/colitis occurred in 12% (62/511) of patients, including Grade 3-5 (7%).

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. Addition of an alternative immunosuppressive agent to the corticosteroid therapy, or replacement of the corticosteroid therapy, should be considered in corticosteroid-refractory immune-mediated colitis if other causes are excluded.

Immune-Mediated Hepatitis

OPDIVO can cause immune-mediated hepatitis. Monitor patients for abnormal liver tests prior to and periodically during treatment. Administer corticosteroids for Grade 2 or greater transaminase elevations. For patients without HCC, withhold OPDIVO for Grade 2 and permanently discontinue OPDIVO for Grade 3 or 4. For patients with HCC, withhold OPDIVO and administer corticosteroids if AST/ALT is within normal limits at baseline and increases to >3 and up to 5 times the upper limit of normal (ULN), if AST/ALT is >1 and up to 3 times ULN at baseline and increases to >5 and up to 10 times the ULN, and if AST/ALT is >3 and up to 5 times ULN at baseline and increases to >8 and up to 10 times the ULN. Permanently discontinue OPDIVO and administer corticosteroids if AST or ALT increases to >10 times the ULN or total bilirubin increases >3 times the ULN.

Contacts

Bristol Myers Squibb
Media Inquiries:
Media@BMS.com
609-252-3345

Investors:
Tim Power

609-252-7509

timothy.power@bms.com

Exelixis
Investors Contact:
Susan Hubbard

EVP, Public Affairs and Investor Relations

(650) 837-8194

shubbard@exelixis.com

Media Contact:
Lindsay Treadway

Senior Director, Public Affairs and Advocacy Relations

(650) 837-7522

ltreadway@exelixis.com

Read full story here

Categories
Healthcare

TYME announces outcome of interim futility review for HopES Sarcoma Phase II study

  • Principal Investigator of the HopES Sarcoma Study Recommended Continuation of the Trial

BEDMINSTER, N.J.–(BUSINESS WIRE)–$TYME—Tyme Technologies, Inc. (NASDAQ: TYME), an emerging biotechnology company developing cancer metabolism-based therapies (CMBTs™), announced today a positive outcome of an interim futility review for the HopES Sarcoma Phase II clinical trial that is evaluating TYME’s lead cancer metabolism-based candidate, SM-88, as a potential oral treatment for patients with Ewing’s Sarcoma and other high-risk sarcomas.

“It is evident that the salvage cohort will pass the futility test and meet the criteria for expansion,” said Sant Chawla, M.D., founder of the Sarcoma Oncology Center, Santa Monica, CA and principal investigator for the HopES Sarcoma trial.

The interim futility review was completed in late July and, based on the analysis of the data and recommendations of Dr. Sant Chawla, the study will proceed with the current trial design as planned. The next major milestone in the HopES Sarcoma trial is expected in calendar year 2021. Sarcomas represents a great unmet medical need and significant opportunity for all stakeholders. There are more than 12,000 patients diagnosed each year without meaningful treatment options.

“We are pleased to have reached this important point in the HopES Sarcoma trial and now await the final results of the trial to determine the potential of oral SM-88 in high-risk sarcomas in an effort to improve the lives of these patients with, what we believe could be, a better safer approach,” said Giuseppe Del Priore, M.D., M.P.H., Chief Medical Officer at TYME. “To date, SM-88 has demonstrated encouraging tumor responses in 15 different cancers across four separate studies with minimal serious grade 3 or higher adverse events.”

The HopES Sarcoma trial is a prospective open-label Phase II trial evaluating the efficacy and safety of SM-88, with the conditioning agents methoxsalen, phenytoin and sirolimus, in two cohorts of patients. Up to 24 evaluable patients (12 per cohort) will be enrolled. The first cohort will evaluate oral SM-88 as maintenance monotherapy following standard primary or palliative treatments for Ewing’s sarcoma patients with a high risk of relapse or disease progression. The second cohort will determine the clinical benefits of SM-88 as salvage monotherapy for patients with clinically advanced sarcomas. Patient dosing began in January 2020. The Joseph Ahmed Foundation is providing funding and patient support for this investigator-initiated Phase II (HopES) trial of SM-88 in patients with previously treated metastatic sarcoma, sponsored by the Sarcoma Oncology Research Center. The primary objectives are to measure efficacy events, including overall response, stable disease and progression free survival. Secondary objectives include duration of response, overall survival, clinical benefit rate using response evaluation criteria in solid tumors (RECIST 1.1), and incidence of treatment-emergent adverse events. Learn more at TYMETRIALS.com.

About Sarcomas and Ewing’s Sarcoma

Sarcomas are rare cancers in adults but are more common in children. There are approximately 12,0001 new sarcoma cases annually in the U.S. alone. There are many “subtypes” of sarcoma, as it can arise in many tissue structures throughout the body (nerves, muscles, joints, bone, fat, blood vessels – collectively referred to as the body’s “connective tissues”). Sarcomas are most frequently found in the limbs, as this is where the majority of the body’s connective tissues are found but can also present within the sites of more “common” cancers (e.g., breast sarcoma, stomach sarcoma, lung sarcoma, ovarian sarcoma, etc.). Sarcoma cancers often grow hidden deep in the body and are often diagnosed when the tumor size limits effective treatment options.

Ewing’s sarcoma is a primary bone cancer within a group of cancers known collectively as the Ewing’s sarcoma family of tumors. Ewing’s sarcoma is a type of tumor that forms in the bone or soft tissue. It is a rare type of cancer that is often overlooked and receives minimal recognition and research funding. Although Ewing’s sarcoma is typically a pediatric cancer, (it accounts for 30% of bone cancers in children), it can also be found in adults. The most commonly affected areas include the pelvis, thigh, lower leg, upper arm, and chest wall.

About SM-88

SM-88 is an oral investigational modified proprietary tyrosine derivative that is believed to interrupt the metabolic processes of cancer cells by breaking down the cells’ key defenses and leading to cell death through oxidative stress and exposure to the body’s natural immune system. Clinical trial data have shown that SM-88 has demonstrated encouraging tumor responses across 15 different cancers, including pancreatic, lung, breast, prostate and sarcoma cancers with minimal serious grade 3 or higher adverse events. SM-88 is an investigational therapy that is not approved for any indication in any disease. Learn more.

About the Joseph Ahmed Foundation

The Joseph Ahmed Foundation (JAF) is a 501(c)(3) non-profit organization that was founded in 2016 by the family of Joseph Ahmed, who lost his courageous battle with Ewing’s Sarcoma eight months after his diagnosis on September 1, 2014, at the age of 16. Through their tragic loss and grief, Joseph’s loved ones established the Joseph Ahmed Foundation which is dedicated to raising public awareness for the importance of early detection of the disease, and the urgent need of funding for research and development of innovative treatment and therapies to treat Ewing’s Sarcoma and other forms of pediatric cancer. JAF’s mission is to provide resources for research programs and support services through fundraising, philanthropic donations, corporate sponsorship and grants. JAF is comprised of passionate board members and volunteers who all share the same vision, finding a cure. The foundation can be reached at 212-867-8667. The global website is www.thejosephahmedfoundation.org

About Tyme Technologies

Tyme Technologies, Inc., is an emerging biotechnology company developing cancer therapeutics that are intended to be broadly effective across tumor types and have low toxicity profiles. Unlike targeted therapies that attempt to regulate specific mutations within cancer, the Company’s therapeutic approach is designed to take advantage of a cancer cell’s innate metabolic weaknesses to compromise its defenses, leading to cell death through oxidative stress and exposure to the body’s natural immune system. For more information, visit www.tymeinc.com. Follow us on social media: @tyme_Inc, LinkedIn, Instagram, Facebook and YouTube.

Forward-Looking Statements/Disclosure Notice

In addition to historical information, this press release contains forward-looking statements under the Private Securities Litigation Reform Act that involve substantial risks and uncertainties. Such forward-looking statements within this press release include, without limitation, statements regarding our drug candidates, including SM-88, and their clinical potential and non-toxic safety profiles, our drug development plans and strategies, ongoing and planned preclinical and clinical trials, preliminary data results and the therapeutic design and mechanisms of our drug candidates; and readers can identify forward-looking statements by sentences or passages involving the use of terms such as “believes,” “expects,” “hopes,” “may,” “will,” “plan,” “intends,” “estimates,” “could,” “should,” “would,” “continue,” “seeks,” or “anticipates,” and similar words including their use in the negative or by discussions of future matters such as effect of the novel coronavirus (COVID-19) pandemic and the associated economic downturn and impacts on the Company’s ongoing preclinical and clinical trials and ability to analyze data from those trials, the cost of development and potential commercialization of our lead drug candidate and of other new products, expected releases of interim or final data from our clinical trials, possible collaborations, the timing, scope and objectives of our ongoing and planned clinical trials and other statements that are not historical. The forward-looking statements contained in this press release are based on management’s current expectations, which are subject to uncertainty, risks and changes in circumstances that are difficult to predict and many of which are outside of TYME’s control. These statements involve known and unknown risks, uncertainties and other factors which may cause the Company’s actual results, performance or achievements to be materially different from any historical results and future results, performances or achievements expressed or implied by the forward-looking statements. These risks and uncertainties include, but are not limited to, the severity, duration, and economic impact of the COVID-19 pandemic; that the information is of a preliminary nature and may be subject to change; uncertainties inherent in the cost and outcomes of research and development, including the cost and availability of acceptable-quality clinical supply and the ability to achieve adequate clinical study design and start and completion dates; the possibility of unfavorable study results, including unfavorable new clinical data and additional analyses of existing data; risks associated with early, initial data, including the risk that the final data from any clinical trial may differ from prior or preliminary study data; final results of additional clinical trials that may be different from the preliminary data analysis and may not support further clinical development; that past reported data are not necessarily predictive of future patient or clinical data outcomes; whether and when any applications or other submissions for SM-88 may be filed with regulatory authorities; whether and when regulatory authorities may approve any applications or submissions; decisions by regulatory authorities regarding labeling and other matters that could affect commercial availability of SM-88; the ability of TYME and its collaborators to develop and realize collaborative synergies; competitive developments; and the factors described in the section captioned “Risk Factors” of TYME’s Annual Report on Form 10-K filed with the U.S. Securities and Exchange Commission on May 22, 2020, as well as subsequent reports we file from time to time with the U.S. Securities and Exchange Commission available at www.sec.gov.

The information contained in this press release is as of its release date and TYME assumes no obligation to update forward-looking statements contained in this release as a result of future events or developments.

1 https://www.cancer.org/cancer/soft-tissue-sarcoma/about/key-statistics.html

Contacts

For Investor Relations & Media Inquiries:

Investor Relations

1-212- 461-2315

investorrelations@tymeinc.com
media@tymeinc.com

Categories
Healthcare

FDA grants priority review to Merck’s New Drug Application for Vericiguat

Application Based on First Contemporary Outcomes Study Focused Exclusively on Chronic Heart Failure Patient Population Following a Worsening Event

KENILWORTH, N.J.–(BUSINESS WIRE)–$MRK #MRK–Merck (NYSE: MRK), known as MSD outside the United States and Canada, announced today that the U.S. Food and Drug Administration (FDA) has accepted for priority review the New Drug Application (NDA) for vericiguat, an orally administered soluble guanylate cyclase (sGC) stimulator, to reduce the risk of cardiovascular death and heart failure hospitalization following a worsening heart failure event in patients with symptomatic chronic heart failure with reduced ejection fraction (HFrEF), in combination with other heart failure therapies. The FDA has set a Prescription Drug User Fee Act (PDUFA), or target action date, of Jan. 20, 2021. Vericiguat is being jointly developed with Bayer AG.

“This submission builds on Merck’s commitment to patients with cardiovascular disease and long legacy of advancing cardiovascular research to meet unmet medical needs,” said Dr. Roy Baynes, senior vice president and head of global clinical development, chief medical officer, Merck Research Laboratories. “We look forward to working with the FDA as they review this New Drug Application for vericiguat.”

The application is based on results from the Phase 3 VICTORIA trial, which is the first contemporary outcomes study focused exclusively on a population with worsening chronic heart failure who are at high risk for cardiovascular mortality and repeated heart failure hospitalizations. Data from VICTORIA were presented at the virtual American College of Cardiology’s 69th Annual Scientific Session together with World Congress of Cardiology (ACC.20/WCC) and published in The New England Journal of Medicine.

About the VICTORIA Trial

VICTORIA (NCT02861534) is a randomized, placebo-controlled, parallel-group, multi-center, double-blind, Phase 3 study of vericiguat versus placebo when given in combination with available heart failure therapies in patients with worsening chronic heart failure (New York Heart Association class II-IV), a reduced left ventricular ejection fraction of <45% within 12 months prior to randomization following a decompensation event. The primary endpoint of the study was the composite of time to first occurrence of heart failure hospitalization or cardiovascular death. Secondary endpoints included time to occurrence of cardiovascular death, time to first occurrence of heart failure hospitalization, time to total heart failure hospitalizations (including first and recurrent events), time to the composite of all-cause mortality or heart failure hospitalization, and time to all-cause mortality.

The study enrolled a total of 5,050 patients who were randomly selected to receive either vericiguat once daily (titrated up to 10 mg) or placebo when given in combination with available heart failure therapies. The study was co-sponsored by Merck and Bayer, conducted under the scientific oversight of the Canadian VIGOUR Centre and the Duke Clinical Research Institute, and executed by Merck in more than 600 centers in 42 countries including in Europe, Japan, China and the U.S.

About Heart Failure with Reduced Ejection Fraction

HFrEF, formerly known as systolic heart failure, is characterized by the compromised ability of the heart to eject blood sufficiently during its contraction phase. In the U.S., 6.5 million people have heart failure, and approximately 40-50% of these patients have HFrEF. Annually, approximately 30% of patients with symptomatic chronic heart failure will experience worsening of the disease, which is marked by progressive symptoms and/or a recent heart failure event. Approximately half of patients with worsening chronic HFrEF are rehospitalized within 30 days of a worsening event, and an estimated one in five patients with worsening chronic HFrEF will die within two years.

About the Worldwide Collaboration Between Bayer and Merck

Since October 2014, Bayer and Merck (known as MSD outside of the United States and Canada) have pursued a worldwide collaboration in the field of sGC modulators. The collaboration brings together two leading companies that have stated their intent to fully evaluate this therapeutic class in areas of unmet medical need. The vericiguat program is being co-developed by Bayer and Merck.

About Merck

For more than 125 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 recent 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 2019 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).

Contacts

Media

Pamela Eisele, (267) 305-3558

Elizabeth Sell, (267) 305-3877

Investor

Peter Dannenbaum, (908) 740-1037

Michael DeCarbo, (908) 740-1807