DARMSTADT, Germany, and NEW YORK, May 9, 2017 /PRNewswire/ --
- Second approval for BAVENCIO in less than two months - Advanced urothelial carcinoma is an aggressive disease with a high rate of recurrence
Merck and Pfizer Inc. today announced that the US Food and Drug Administration (FDA) has approved BAVENCIO(R) (avelumab) Injection for the treatment of patients with locally advanced or metastatic urothelial carcinoma (UC) who have disease progression during or following platinum-containing chemotherapy therapy, or who have disease progression within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy. BAVENCIO was previously granted accelerated approval from the FDA for the treatment of adults and pediatric patients 12 years and older with metastatic Merkel cell carcinoma (MCC). These indications are approved under accelerated approval based on tumor response and duration of response. Continued approval for these indications may be contingent upon verification and description of clinical benefit in confirmatory trials.[1] BAVENCIO will be co-commercialized by EMD Serono, the biopharmaceutical business of Merck in the US and Canada, and Pfizer.
"This approval for BAVENCIO in patients with locally advanced or metastatic urothelial carcinoma exemplifies our unwavering commitment to finding new treatments for the most challenging cancers," said Luciano Rossetti, M.D., Executive Vice President, Global Head of Research & Development at biopharma business of Merck. "Coming just a few weeks after the approval for metastatic Merkel cell carcinoma, we continue to demonstrate our ability to accelerate access to innovative medicines for patients in need."
"This approval builds on the ongoing clinical development program for BAVENCIO in urothelial carcinoma and reinforces our commitment to providing new medicines to patients with difficult-to-treat cancers," said Liz Barrett, Global President, Pfizer Oncology. "By drawing on the strength of the alliance, as well as Pfizer's deep experience in genitourinary cancers, we believe BAVENCIO will be an important treatment option, and we hope it will help to improve outcomes for these patients."
Bladder cancer makes up approximately 90% of urothelial carcinomas and is the sixth most common cancer in the US.[2],[3] When the disease has metastasized, the five-year survival rate is approximately 5%.[4] Despite advances in the treatment of locally advanced or metastatic urothelial carcinoma, the prognosis for patients remains poor and more treatment options are needed.[2]
"Once urothelial carcinoma progresses after treatment with chemotherapy, the five-year survival rate is alarmingly low," said Dr. Andrea Apolo, National Cancer Institute, Bethesda, MD. "Until recently, there had been limited innovation in urothelial carcinoma, and this approval gives us another treatment to help battle this aggressive disease."
The efficacy and safety of BAVENCIO was demonstrated in the urothelial carcinoma cohorts (N=242) of the JAVELIN Solid Tumor trial, a Phase I, open-label, single-arm, multicenter study of BAVENCIO in the treatment of various solid tumors. The urothelial carcinoma cohorts enrolled patients with locally advanced or metastatic urothelial carcinoma with disease progression on or after platinum-containing chemotherapy or who had disease progression within 12 months of treatment with a platinum-containing neoadjuvant or adjuvant chemotherapy regimen. These data will be presented at an upcoming medical congress.
The warnings and precautions for BAVENCIO include immune-mediated adverse reactions (such as pneumonitis, hepatitis, colitis, endocrinopathies, nephritis and renal dysfunction and other adverse reactions), infusion-related reactions and embryo-fetal toxicity. The most common adverse reactions (reported in at least 20% of patients) in patients with locally advanced or metastatic urothelial carcinoma were fatigue (41%), infusion-related reaction (30%), musculoskeletal pain (25%), nausea (24%), decreased appetite/hypophagia (21%) and urinary tract infection (21%).[1] For more information, please see Important Safety Information for BAVENCIO below.
BAVENCIO is designed to potentially engage both the adaptive and innate immune systems. By binding to PD-L1, BAVENCIO is thought to prevent tumor cells from using PD-L1 for protection against white blood cells, such as T cells, exposing them to anti-tumor responses.[1] BAVENCIO has also been shown to induce antibody-dependent cell-mediated cytotoxicity (ADCC) in vitro.[1]
The alliance is committed to providing industry-leading patient access and reimbursement support through its CoverOne(TM) program in the United States. This program provides a spectrum of patient access and reimbursement support services intended to help patients receive appropriate access to BAVENCIO in the United States.
About Urothelial Carcinoma Cohorts in JAVELIN Solid Tumor Trial
The efficacy and safety of BAVENCIO was demonstrated in the urothelial carcinoma cohorts of the JAVELIN Solid Tumor trial, a Phase I, open-label, single-arm, multicenter study that included 242 patients with locally advanced or metastatic urothelial carcinoma with disease progression on or after platinum-containing chemotherapy or who had disease progression within 12 months of treatment with a platinum-containing neoadjuvant or adjuvant chemotherapy regimen who were treated with BAVENCIO.
Patients with active or a history of central nervous system metastasis; other malignancies within the last five years; an organ transplant; conditions requiring therapeutic immune suppression; or active infection with HIV, hepatitis B or C were excluded. Patients with autoimmune disease, other than type 1 diabetes, vitiligo, psoriasis, or thyroid disease that did not require immunosuppressive treatment, were excluded. Patients were included regardless of their PD-L1 status. Patients received BAVENCIO at a dose of 10 mg/kg intravenously over 60 minutes every two weeks until disease progression or unacceptable toxicity. Tumor response assessments were performed every six weeks, as assessed by an Independent Endpoint Review Committee (IERC) using Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. Efficacy outcome measures included confirmed overall response rate (ORR) and duration of response (DOR). Efficacy measures were evaluated in patients who were followed for a minimum of both 13 weeks and 6 months at the time of data cut-off.
Out of the total 226 patients evaluable for efficacy, 44% had non-bladder urothelial carcinoma, including 23% of patients with upper tract disease; 83% of patients had visceral metastases; 34% of patients had liver metastases. Nine patients (4%) had disease progression following prior platinum-containing neoadjuvant or adjuvant therapy only. Forty-seven percent of patients only received prior cisplatin-based regimens, 32% received only prior carboplatin-based regimens, and 20% received both cisplatin and carboplatin-based regimens.
The international clinical development program for avelumab, known as JAVELIN, involves more than 30 clinical programs, including nine Phase III trials, and more than 5,200 patients across more than 15 tumor types.
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