Merck and Pfizer Inc. today announced that the European Commission (EC) has approved BAVENCIO? (avelumab) as monotherapy for the first-line maintenance treatment of adult patients with locally advanced or metastatic urothelial carcinoma (UC) who are progression-free following platinum-based chemotherapy.

"Avelumab is the only immunotherapy to demonstrate a significant improvement in overall survival in the first-line setting in a Phase III study in advanced or metastatic bladder cancer. With this approval by the European Commission, we can now offer patients a potential new first-line maintenance standard of care that may help them live longer," said Professor Thomas Powles, MD, Director of Barts Cancer Centre, London, UK.

In the pivotal JAVELIN Bladder 100 trial, BAVENCIO plus best supportive care (BSC) as first-line maintenance demonstrated a significant improvement in median overall survival (OS) vs BSC alone at the prespecified interim analysis (data cut-off date Oct. 21, 2019): 21.4 months (95% CI: 18.9 to 26.1) vs 14.3 months (95% CI: 12.9 to 17.8) in the coprimary population of all randomized patients (HR 0.69; 95% CI: 0.56 to 0.86).1 In the coprimary population of patients with PD-L1+ tumors (n=358), OS was also significantly longer with BAVENCIO plus BSC (median not reached; 95% CI: 20.3, not reached) vs BSC alone (17.1 months; 95% CI: 13.5, 23.7; HR 0.56; 95% CI, 0.40 to 0.79).1,2 Based on these data, the BAVENCIO first-line maintenance regimen was added to the recently updated ESMO Clinical Practice Guidelines for bladder cancer.3

Updated OS results with a data cut-off of Jan. 19, 2020 also showed BAVENCIO significantly extended OS among all randomized patients vs BSC alone (HR 0.70; 95% CI, 0.56 to 0.86; two-sided P=0.0008), with median OS of 22.1 months (95% CI, 19.0 to 26.1) vs 14.6 months (95% CI, 12.8 to 17.8), respectively.1 

"Today's announcement is the latest example of our decades-long commitment to developing new treatments for people with genitourinary cancers," said Andy Schmeltz, Global President, Pfizer Oncology. "This approval by the EC addresses an urgent unmet need, and we look forward to providing a new treatment option for people in Europe with locally advanced or metastatic urothelial carcinoma."   

"This approval allows us to extend the reach of BAVENCIO to even more patients with bladder cancer and offer the hope of extended survival," said Rehan Verjee, President of North America and Global Head of Innovative Medicine Franchises for the Healthcare business sector of Merck. "This is a clear demonstration of our commitment to transform standards of care in cancer."

BAVENCIO was first approved in the US as a first-line maintenance treatment for advanced UC by the US Food and Drug Administration (FDA) in June 2020 and is now approved for this indication in 38 countries. Additional regulatory applications are under review in 13 countries, including in Japan, where approval is expected in H1 2021.

About Advanced Urothelial Carcinoma

Bladder cancer is the tenth most common cancer worldwide.4 Nearly 204,000 people in Europe were diagnosed with bladder cancer across all stages in 2020, and more than 67,000 patients died from the disease, despite available treatments.4 UC is the most common form of bladder cancer, accounting for about 90% of cases.5 UC becomes harder to treat as it advances.6 For patients diagnosed with metastatic UC, the five-year survival rate is 5%.7

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

The European Commission (EC) has authorized the use of BAVENCIO as monotherapy for the first-line maintenance treatment of adult patients with locally advanced or metastatic urothelial carcinoma (UC) who are progression-free following platinum-based chemotherapy. BAVENCIO in combination with axitinib is indicated 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).

In the US, BAVENCIO is indicated for the maintenance treatment of patients with locally advanced or metastatic urothelial carcinoma (UC) that has not progressed with first-line platinum-containing chemotherapy. BAVENCIO is also indicated for the treatment of patients with locally advanced or metastatic UC 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.

BAVENCIO in combination with axitinib is indicated in the US for the first-line treatment of patients with advanced RCC. Additionally, the US Food and Drug Administration (FDA) granted accelerated approval for BAVENCIO for the treatment of adults and pediatric patients 12 years and older with metastatic MCC. 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.

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)

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. The list of most common adverse reactions with BAVENCIO in combination with axitinib includes diarrhea, hypertension, fatigue, nausea, dysphonia, decreased appetite, hypothyroidism, cough, headache, dyspnea, and arthralgia.

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.

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. 

References

BAVENCIO? (avelumab) EU SmPC. http://www.ema.europa.eu/ema/. Accessed February 2021.

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.

ESMO.org. eUpdate- Bladder cancer treatment recommendations. https://www.esmo.org/guidelines/genitourinary-cancers/bladder-cancer/eupdate-bladder-cancer-treatment-recommendations4. Accessed January 2021. 

IARC. Bladder Fact Sheet: GLOBOCAN. https://gco.iarc.fr/today/data/factsheets/cancers/30-Bladder-fact-sheet.pdf. Accessed January 2021.

Cancer.net. Bladder cancer: introduction. https://www.cancer.net/cancer-types/bladder-cancer/introduction. Accessed January 2021.

American Cancer Society. What is bladder cancer? https://www.cancer.org/cancer/bladder-cancer/about/what-is-bladder-cancer.html. Accessed January 2021.

SEER. Cancer stat facts: bladder cancer. https://seer.cancer.gov/statfacts/html/urinb.html.  Accessed January 2021.

Dolan DE, Gupta S. PD-1 pathway inhibitors: changing the landscape of cancer immunotherapy. Cancer Control. 2014;21(3):231-237.

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.

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.