Tag: Phase II

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Healthcare

Bayer and Orion expand development program for NUBEQA® (darolutamide) in prostrate cancer

  •  Phase III study ARANOTE to be initiated in metastatic hormone-sensitive prostate cancer (mHSPC) assessing the androgen receptor inhibitor (ARi) in combination with standard androgen deprivation therapy (ADT)
  • Start of patient enrollment expected by the end of Q1 2021
  • Study adds to the robust development program for NUBEQA, exploring an opportunity to help even more patients with prostate cancer

WHIPPANY, N.J. — (BUSINESS WIRE) — Bayer and Orion Corporation are expanding the global clinical development program for the oral androgen receptor inhibitor (ARi) NUBEQA® (darolutamide) in prostate cancer. A new Phase III study ARANOTE will investigate NUBEQA in addition to androgen deprivation therapy (ADT) versus placebo plus ADT in men with metastatic hormone-sensitive prostate cancer (mHSPC). The study builds on the robust development program comprising multiple studies, including the Phase III study ARASENS, which investigates NUBEQA combined with ADT and docetaxel compared to docetaxel and ADT alone in men with mHSPC.

“NUBEQA has already shown in men with non-metastatic castration-resistant prostate cancer (nmCRPC) that it extends metastasis-free and overall survival,” said Scott Z. Fields, M.D., Senior Vice President and Head of Oncology Development at Bayer’s Pharmaceutical Division. “Given the encouraging results that we have seen with NUBEQA so far, it is important that we also evaluate the potential of NUBEQA in other stages of prostate cancer that may offer men with mHSPC a new treatment option.”

In 2019, NUBEQA was approved in the U.S. for the treatment of patients with nmCRPC. The ARAMIS study demonstrated proven efficacy and tolerability, including significant improvement in metastasis-free survival (MFS). NUBEQA plus ADT showed the same low rate of permanent discontinuation due to adverse reactions compared to ADT alone (9% versus 9%). The most frequent adverse reactions requiring discontinuation in patients who received NUBEQA included cardiac failure (0.4%), and death (0.4%). Adverse reactions occurring more frequently in the NUBEQA arm (≥2% over placebo) were fatigue (16% versus 11%), pain in extremity (6% versus 3%) and rash (3% versus 1%). NUBEQA was not studied in women and there is a warning and precaution for embryo-fetal toxicity.1

About the ARANOTE Trial

The ARANOTE trial will be a randomized, double-blind, placebo-controlled Phase III study of NUBEQA in addition to androgen deprivation therapy (ADT) versus placebo plus ADT in men with metastatic hormone-sensitive prostate cancer (mHSPC). The primary endpoint of this study is radiological progression-free survival (rPFS), as measured as the time from the date of randomization to the date of first documentation of radiological progressive disease or death due to any cause, whichever occurs first. The trial is expected to enroll about 555 men, with the first patients enrolled by the end of Q1 2021.

Data from the Phase III ARAMIS Trial

Previously published in The New England Journal of Medicine, results in 1,509 patients from the Phase III ARAMIS trial demonstrated a highly significant improvement in the primary efficacy endpoint of metastasis-free survival (MFS), with a median of 40.4 months (n=955) with NUBEQA plus androgen deprivation therapy (ADT), more than double the 18.4 months (n=554) for placebo plus ADT (p<0.001). MFS is defined as the time from randomization to the time of first evidence of blinded independent central review (BICR)-confirmed distant metastasis or death from any cause within 33 weeks after the last evaluable scan, whichever occurred first.1

Additionally, NUBEQA plus ADT showed a statistically significant improvement in the secondary endpoint of overall survival (OS) compared to placebo plus ADT, with a 31% reduction in risk of death (HR=0.69, 95% CI 0.53-0.88; p=0.003). OS was statistically significant despite 31% (n=170) of patients in the ADT arm crossing over to NUBEQA. In total, 55% (n=307) of patients in the ADT arm crossed over to NUBEQA or received another life-prolonging therapy prior to this analysis.1

Dose interruptions due to an adverse reaction occurred in 13% of patients treated with NUBEQA. The most frequent adverse reactions requiring dosage interruption in patients who received NUBEQA included hypertension (0.6%), diarrhea (0.5%), and pneumonia (0.5%). Dose reductions due to an adverse reaction occurred in 6% of patients treated with NUBEQA. The most frequent adverse reactions requiring dosage reduction in patients treated with NUBEQA included fatigue (0.7%), hypertension (0.3%), and nausea (0.3 %).1

About NUBEQA® (darolutamide)1

NUBEQA is an androgen receptor inhibitor (ARi) with a distinct chemical structure that competitively inhibits androgen binding, AR nuclear translocation, and AR-mediated transcription.1 A Phase III study in metastatic hormone-sensitive prostate cancer (ARASENS) is ongoing. Information about this trial can be found at www.clinicaltrials.gov.

Developed jointly by Bayer and Orion Corporation, a globally operating Finnish pharmaceutical company, NUBEQA is indicated for the treatment of men with nmCRPC.1 The approvals of NUBEQA in the U.S., European Union (EU), and other global markets have been based on the pivotal Phase III ARAMIS trial data evaluating the efficacy and safety of NUBEQA plus androgen deprivation therapy (ADT) compared to ADT alone.1 Filings in other regions are underway or planned.

INDICATION FOR NUBEQA (darolutamide)

NUBEQA® (darolutamide) is an androgen receptor inhibitor indicated for the treatment of patients with non-metastatic castration-resistant prostate cancer.

IMPORTANT SAFETY INFORMATION FOR NUBEQA (darolutamide)

Embryo-Fetal Toxicity: Safety and efficacy of NUBEQA have not been established in females. NUBEQA can cause fetal harm and loss of pregnancy. Advise males with female partners of reproductive potential to use effective contraception during treatment with NUBEQA and for 1 week after the last dose.

Adverse Reactions

Serious adverse reactions occurred in 25% of patients receiving NUBEQA and in 20% of patients receiving placebo. Serious adverse reactions in ≥1 % of patients who received NUBEQA were urinary retention, pneumonia, and hematuria. Overall, 3.9% of patients receiving NUBEQA and 3.2% of patients receiving placebo died from adverse reactions, which included death (0.4%), cardiac failure (0.3%), cardiac arrest (0.2%), general physical health deterioration (0.2%), and pulmonary embolism (0.2%) for NUBEQA.

Adverse reactions occurring more frequently in the NUBEQA arm (≥2% over placebo) were fatigue (16% vs 11%), pain in extremity (6% vs 3%) and rash (3% vs 1%).

Clinically significant adverse reactions occurring in ≥2% of patients treated with NUBEQA included ischemic heart disease (4.0% vs 3.4% on placebo) and heart failure (2.1% vs 0.9% on placebo).

Drug Interactions

Effect of Other Drugs on NUBEQA – Combined P-gp and strong or moderate CYP3A4 inducers decrease NUBEQA exposure, which may decrease NUBEQA activity. Avoid concomitant use.

Combined P-gp and strong CYP3A4 inhibitors increase NUBEQA exposure, which may increase the risk of NUBEQA adverse reactions. Monitor more frequently and modify NUBEQA dose as needed.

Effects of NUBEQA on Other Drugs – NUBEQA inhibits breast cancer resistance protein (BCRP) transporter. Concomitant use increases exposure (AUC) and maximal concentration of BCRP substrates, which may increase the risk of BCRP substrate-related toxicities. Avoid concomitant use where possible. If used together, monitor more frequently for adverse reactions, and consider dose reduction of the BCRP substrate.

NUBEQA inhibits OATP1B1 and OATP1B3 transporters. Concomitant use may increase plasma concentrations of OATP1B1 or OATP1B3 substrates. Monitor more frequently for adverse reactions and consider dose reduction of these substrates.

Review the prescribing information of drugs that are BCRP, OATP1B1, and OATP1B3 substrates when used concomitantly with NUBEQA.

For important risk and use information about NUBEQA, please see the accompanying full Prescribing Information.

About Metastatic Hormone-Sensitive Prostate Cancer

Prostate cancer is the second most commonly diagnosed malignancy in men worldwide. In 2018, an estimated 1.2 million men were diagnosed with prostate cancer, and about 358,000 died from the disease worldwide.2

At the time of diagnosis, most men have localized prostate cancer, meaning their cancer is confined to the prostate gland and can be treated with curative surgery or radiotherapy.3,4 Upon relapse when the disease will metastasize or spread, androgen deprivation therapy (ADT) is the cornerstone of treatment for this hormone-sensitive disease. Approximately five percent of men will already suffer from prostate cancer with distant metastases when first diagnosed. Men with metastatic hormone-sensitive prostate cancer (mHSPC) will start their treatment with hormone therapy, such as ADT, androgen receptor inhibitor (ARi) plus ADT or a combination of the chemotherapy docetaxel and ADT. Despite this first-line treatment, most men with mHSPC will eventually progress to metastatic castration-resistant prostate cancer (mCRPC), which can impact survival.5,6

About Oncology at Bayer

Bayer is committed to delivering science for a better life by advancing a portfolio of innovative treatments. The oncology franchise at Bayer now expands to six marketed products and several other assets in various stages of clinical development. Together, these products reflect the company’s approach to research, which prioritizes targets and pathways with the potential to impact the way that cancer is treated.

About Bayer

Bayer is a global enterprise with core competencies in the life science fields of health care and nutrition. Its products and services are designed to benefit people by supporting efforts to overcome the major challenges presented by a growing and aging global population. At the same time, the Group aims to increase its earning power and create value through innovation and growth. Bayer is committed to the principles of sustainable development, and the Bayer brand stands for trust, reliability and quality throughout the world. In fiscal 2019, the Group employed around 104,000 people and had sales of 43.5 billion euros. Capital expenditures amounted to 2.9 billion euros, R&D expenses to 5.3 billion euros. For more information, go to www.bayer.us.

© 2021 Bayer

BAYER, the Bayer Cross and NUBEQA are registered trademarks of Bayer.

Forward-Looking Statements

This release may contain forward-looking statements based on current assumptions and forecasts made by Bayer management. Various known and unknown risks, uncertainties and other factors could lead to material differences between the actual future results, financial situation, development or performance of the company and the estimates given here. These factors include those discussed in Bayer’s public reports which are available on the Bayer website at www.bayer.com. The company assumes no liability whatsoever to update these forward-looking statements or to conform them to future events or developments.

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References

  1. NUBEQA® (darolutamide) tablets [Prescribing Information]. Whippany, NJ: Bayer HealthCare Pharmaceuticals, January 2021.
  2. GLOBOCAN 2018: Estimated Cancer Incidence, Mortality and Prevalence Worldwide in 2018. CA: A Cancer Journal for Clinicians. https://onlinelibrary.wiley.com/doi/epdf/10.3322/caac.21492. Accessed February 2021.
  3. Cancer.Net 2020: Prostate Cancer Statistics. https://www.cancer.net/cancer-types/prostate-cancer/statistics. Accessed February 2021.
  4. American Cancer Society: Hormone Therapy for Prostate Cancer. https://www.cancer.org/cancer/prostate-cancer/treating/hormone-therapy.html. Accessed February 2021.
  5. Siegel DA, O’Neil ME, Richards TB, Dowling NF, Weir HK. Prostate Cancer Incidence and Survival, by Stage and Race/Ethnicity — United States, 2001–2017. MMWR Morb Mortal Wkly Rep 2020;69:1473–1480. http://dx.doi.org/10.15585/mmwr.mm6941a1.
  6. Ng, K., Smith, S., Shamash, J. Metastatic Hormone-Sensitive Prostate Cancer (mHSPC): Advances and Treatment Strategies in the First-Line Setting. Oncol Ther 8, 209–230 (2020). https://doi.org/10.1007/s40487-020-00119-z.

PP-NUB-US-0940-1

Contacts

Rose Talarico, Tel. +1 862.404.5302

E-Mail: rose.talarico@bayer.com

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

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