BAVENCIO® (avelumab) Receives Positive CHMP Opinion for First-Line Maintenance Treatment of Locally Advanced or Metastatic Urothelial Carcinoma

Merck and Pfizer today announced that the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) adopted a positive opinion recommending approval of BAVENCIO^® (avelumab) as monotherapy for the first‑line maintenance treatment of adult patients with locally advanced or metastatic urothelial carcinoma (UC) whose disease has not progressed with platinum‑based induction chemotherapy. The CHMP positive opinion will now be reviewed by the European Commission (EC), with a decision expected in early 2021.

The opinion was based on positive findings from the Phase III JAVELIN Bladder 100 trial, results of which were published in The New England Journal of Medicine in September 2020.¹ BAVENCIO is the only immunotherapy to significantly prolong overall survival (OS) in locally advanced or metastatic UC in the first-line maintenance setting in a Phase III trial.

Dr Simon Crabb, Associate Professor in Medical Oncology, University of Southampton explains, “The prognosis and quality of life for patients with urothelial carcinoma is unacceptably poor. Despite high response rates to first-line platinum-based chemotherapy treatment, which is the current standard of care, it has limited durability and most patients will ultimately experience disease progression within nine months of initiation of treatment. Introducing BAVENCIO as a first-line maintenance treatment after chemotherapy can sustain and extend the benefits of treatment and significantly prolong overall survival, compared to best supportive care, without a detrimental impact on a patient’s quality of life. I believe this strategy will now change clinical practice for the treatment of patients with locally advanced or metastatic urothelial carcinoma.”

“BAVENCIO is the only immunotherapy treatment to demonstrate in the first-line maintenance setting the ability to help patients with locally advanced or metastatic urothelial carcinoma live longer,” said Danny Bar-Zohar, MD, Global Head of Development for the Biopharma business of Merck KGaA, Darmstadt, Germany. “Now with this positive opinion, we have come a big step closer to being able to offer a new option that may shift the treatment paradigm for patients in Europe.”

Based on 2018 results, bladder cancer is the tenth most common cancer worldwide.² In 2018 in Europe alone, nearly 200,000 people were diagnosed with bladder cancer and more than 60,000 patients died from the disease, despite available treatments.³ UC, which accounts for about 90% of all bladder cancers, becomes harder to treat as it advances, spreading through the layers of the bladder wall.^4,5 For patients with advanced UC, the five-year survival rate is 5%.⁶ About 4% of bladder cancers are diagnosed at an advanced stage. ⁷ 

“Patients living with locally advanced or metastatic urothelial carcinoma in Europe are in urgent need of more treatment options that have the potential to extend their lives,” said Chris Boshoff, M.D., Ph.D., Chief Development Officer, Oncology, Pfizer Global Product Development. “The overall survival results from JAVELIN Bladder 100 show the potential benefits of a first-line maintenance approach with BAVENCIO as a significant advancement for patients with locally advanced or metastatic urothelial carcinoma.”

Avelumab is not licensed in the UK as monotherapy for the first line maintenance treatment of adult patients with locally advanced or metastatic urothelial carcinoma (UC) whose disease has not progressed with platinum-based induction chemotherapy and a marketing authorisation application for this indication is currently under review by the European Medicines Agency (EMA).

This medicine is subject to additional monitoring. This will allow quick identification of new safety information. Healthcare professionals are asked to report any suspected adverse events.  Reporting forms and information can be found at mhra.gov.uk/yellowcard. Adverse events should also be reported to Merck Serono Limited on 0208 818 7373 (email: medinfo.uk@merckgroup.com).

About JAVELIN Bladder 100

JAVELIN Bladder 100 (NCT02603432) is a Phase III, multicenter, multinational, randomized, open-label, parallel-arm study investigating first-line maintenance treatment with BAVENCIO plus best supportive care (BSC) versus BSC alone in patients with locally advanced or metastatic UC. A total of 700 patients whose disease had not progressed after platinum-based induction chemotherapy as per RECIST v1.1 were randomly assigned to receive either BAVENCIO plus BSC or BSC alone. The primary endpoint was OS in the two primary populations of all patients and patients with PD-L1+ tumors.

About BAVENCIO^® (avelumab)

BAVENCIO is a human anti-programmed death ligand-1 (PD-L1) antibody. BAVENCIO has been shown in preclinical models to engage both the adaptive and innate immune functions. By blocking the interaction of PD-L1 with PD-1 receptors, BAVENCIO has been shown to release the suppression of the T cell-mediated antitumor immune response in preclinical models.^8-10 In November 2014, Merck and Pfizer announced a strategic alliance to co-develop and co-commercialize BAVENCIO. 

BAVENCIO Approved Indications in Europe

The European Commission (EC) has authorized the use of BAVENCIO in combination with axitinib for the first-line treatment of adult patients with advanced renal cell carcinoma (RCC). BAVENCIO is also authorized by the EC for use as a monotherapy for the treatment of adult patients with metastatic Merkel cell carcinoma (MCC).¹¹

BAVENCIO is currently approved for patients in 50 countries for at least one use.

BAVENCIO Safety Profile from the EU Summary of Product Characteristics (SmPC)¹¹

The special warnings and precautions for use for BAVENCIO monotherapy include infusion-related reactions, as well as immune-related adverse reactions that include pneumonitis and hepatitis (including fatal cases), colitis, pancreatitis (including fatal cases), myocarditis (including fatal cases), endocrinopathies, nephritis and renal dysfunction, and other immune-related adverse reactions. The special warnings and precautions for use for BAVENCIO in combination with axitinib include hepatotoxicity.

The SmPC list of the most common adverse reactions with BAVENCIO monotherapy in patients with solid tumors includes fatigue, nausea, diarrhea, decreased appetite, constipation, infusion-related reactions, weight decreased and vomiting.

About Merck-Pfizer Alliance

Immuno-oncology is a top priority for Merck and Pfizer. The global strategic alliance between Merck and Pfizer enables the companies to benefit from each other’s strengths and capabilities and further explore the therapeutic potential of BAVENCIO, an anti-PD-L1 antibody initially discovered and developed by Merck. The immuno-oncology alliance is jointly developing and commercializing BAVENCIO. The alliance is focused on developing high-priority international clinical programs to investigate BAVENCIO as a monotherapy as well as combination regimens, and is striving to find new ways to treat cancer.

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About Merck

Merck, a leading science and technology company, operates across healthcare, life science and performance materials. Around 57,000 employees work to make a positive difference to millions of people’s lives every day by creating more joyful and sustainable ways to live. From advancing gene editing technologies and discovering unique ways to treat the most challenging diseases to enabling the intelligence of devices – the company is everywhere. In 2019, Merck generated sales of € 16.2 billion in 66 countries.

Scientific exploration and responsible entrepreneurship have been key to Merck’s technological and scientific advances. This is how Merck has thrived since its founding in 1668. The founding family remains the majority owner of the publicly listed company. Merck holds the global rights to the Merck name and brand. The only exceptions are the United States and Canada, where the business sectors of Merck operate as EMD Serono in healthcare, MilliporeSigma in life science, and EMD Performance Materials.

Pfizer Inc.: Breakthroughs that change patients’ lives

At Pfizer, we apply science and our global resources to bring therapies to people that extend and significantly improve their lives. We strive to set the standard for quality, safety and value in the discovery, development and manufacture of health care products, including innovative medicines and vaccines. Every day, Pfizer colleagues work across developed and emerging markets to advance wellness, prevention, treatments and cures that challenge the most feared diseases of our time. Consistent with our responsibility as one of the world's premier innovative biopharmaceutical companies, we collaborate with health care providers, governments and local communities to support and expand access to reliable, affordable health care around the world. For more than 150 years, we have worked to make a difference for all who rely on us. We routinely post information that may be important to investors on our website at www.pfizer.com. In addition, to learn more, please visit us on www.pfizer.com and follow us on Twitter at @Pfizer and @Pfizer_News, LinkedIn, YouTube and like us on Facebook at Facebook.com/Pfizer.

Pfizer Disclosure Notice

The information contained in this release is as of 11 December 2020. Pfizer assumes no obligation to update forward-looking statements contained in this release as the result of new information or future events or developments.

This release contains forward-looking information about BAVENCIO (avelumab), including an indication for first-line maintenance therapy for BAVENCIO for the treatment of patients with locally advanced or metastatic urothelial carcinoma, the alliance between Merck and Pfizer involving BAVENCIO and clinical development plans, including their potential benefits, that involves substantial risks and uncertainties that could cause actual results to differ materially from those expressed or implied by such statements. Risks and uncertainties include, among other things, uncertainties regarding the commercial success of BAVENCIO; the uncertainties inherent in research and development, including the ability to meet anticipated clinical endpoints, commencement and/or completion dates for our clinical trials, regulatory submission dates, regulatory approval dates and/or launch dates, as well as the possibility of unfavorable new clinical data and further analyses of existing clinical data; risks associated with interim data; the risk that clinical trial data are subject to differing interpretations and assessments by regulatory authorities; whether regulatory authorities will be satisfied with the design of and results from our clinical studies; whether and when any drug applications may be filed in any other jurisdictions for BAVENCIO for first-line maintenance therapy for locally advanced or metastatic urothelial carcinoma in any jurisdictions or for any other potential indications for BAVENCIO or combination therapies in any jurisdictions; whether and when regulatory authorities in any jurisdictions where any applications are pending or may be submitted for BAVENCIO or combination therapies, including BAVENCIO for locally advanced or metastatic urothelial carcinoma may approve any such applications, which will depend on myriad factors, including making a determination as to whether the product’s benefits outweigh its known risks and determination of the product’s efficacy, and, if approved, whether they will be commercially successful; decisions by regulatory authorities impacting labeling, manufacturing processes, safety and/or other matters that could affect the availability or commercial potential of BAVENCIO, including BAVENCIO for locally advanced or metastatic urothelial carcinoma; the impact of COVID-19 on our business, operations and financial results; and competitive developments.

A further description of risks and uncertainties can be found in Pfizer’s Annual Report on Form 10-K for the fiscal year ended December 31, 2019, and in its subsequent reports on Form 10-Q, including in the sections thereof captioned “Risk Factors” and “Forward-Looking Information and Factors That May Affect Future Results”, as well as in its subsequent reports on Form 8-K, all of which are filed with the U.S. Securities and Exchange Commission and available at www.sec.gov and www.pfizer.com.

References

1. Powles T, Park SH, Voog E, et al. Avelumab maintenance therapy for advanced or metastatic urothelial cancer. N Engl J Med. 2020;383:1218-1230.
2. Bray F, et al. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA: A Cancer Journal. 2018;68(6):394-424.
3. Cancer Today. Estimated number of new cases in 2018, Europe, both sexes, all ages. https://gco.iarc.fr/today/online-analysis-tables. Accessed September 2020.
4. Cancer.net. Bladder cancer: introduction. https://www.cancer.net/cancer-types/bladder-cancer/introduction. Accessed August 2020.
5. American Cancer Society. What is bladder cancer? https://www.cancer.org/cancer/bladder-cancer/about/what-is-bladder-cancer.html. Accessed September 2020.
6. SEER. Cancer stat facts: bladder cancer. https://seer.cancer.gov/statfacts/html/urinb.html.  Accessed September 2020.
7. Cancer.net. Bladder cancer: statistics. https://www.cancer.net/cancer-types/bladder-cancer/statistics. Accessed September 2020.
8. Dolan DE, Gupta S. PD-1 pathway inhibitors: changing the landscape of cancer immunotherapy. Cancer Control. 2014;21(3):231-237.
9. Dahan R, Sega E, Engelhardt J, et al. FcγRs modulate the anti-tumor activity of antibodies targeting the PD-1/PD-L1 axis. Cancer Cell. 2015;28(3):285-295.
10. Boyerinas B, Jochems C, Fantini M, et al. Antibody-dependent cellular cytotoxicity activity of a novel anti-PD-L1 antibody avelumab (MSB0010718C) on human tumor cells. Cancer Immunol Res. 2015;3(10):1148-1157.
11. BAVENCIO® (avelumab) SmPC. https://www.medicines.org.uk/emc/product/8453/smpc. Last updated on EMC: 30 September 2020. Accessed December 2020.

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Date of preparation: December 2020