KENILWORTH, N.J.--(BUSINESS WIRE)--MSD, known as Merck in the United States and Canada, today announced that the European Commission has approved KEYTRUDA® (pembrolizumab), the company’s anti-PD-1 therapy, for the treatment of advanced (unresectable or metastatic) melanoma in adults. The European Commission approval of pembrolizumab is based on data from three clinical studies conducted in more than 1,500 first-line and previously-treated patients with advanced melanoma. Pembrolizumab received European Commission regulatory approval based on Phase 3 data which showed it is the first and only anti-PD-1 therapy to provide a statistically superior survival benefit as a monotherapy compared to ipilimumab, the current standard of care for advanced melanoma. Today’s approval allows marketing of pembrolizumab in all 28 EU member states at the approved dose of 2 mg/kg every three weeks.
“Today’s European approval supports our goal of accelerating immuno-oncology research for the benefit of patients around the world,” said Dr. Roger M. Perlmutter, president, Merck Research Laboratories. “We believe that the broad data set supporting this approval helps illustrate the significant potential of pembrolizumab to treat advanced melanoma, a devastating disease.”
“MSD has long-believed that innovation and access must go hand-in-hand, which is why we work to bring forward new innovations, and ensure access to those innovations,” said Deepak Khanna, senior vice president and regional president, Europe, MSD Oncology. “MSD is committed to working collaboratively with governments and other stakeholders to ensure that pembrolizumab will be made available to advanced melanoma patients in Europe as rapidly as possible.”
About KEYNOTE-001, 002 and 006
The European Commission’s approval is based on data from three studies -- KEYNOTE-001, KEYNOTE-002 and KEYNOTE-006. These studies evaluated the efficacy and safety of pembrolizumab in advanced melanoma patients – across treatment lines, prognostic factors, tumor characteristics, and BRAF mutational status – and established 2 mg/kg every three weeks as the approved dose.
KEYNOTE-001, the largest Phase 1b study to date of an anti-PD-1 antibody, is a single arm, open label study of pembrolizumab (2 mg/kg every three weeks or 10 mg/kg every two or three weeks) that included patients with advanced melanoma who were previously-treated with ipilimumab (and, if BRAF V600 mutation-positive, a BRAF or MEK inhibitor) and patients who were ipilimumab-naïve. In two cohorts of advanced melanoma patients comparing doses of pembrolizumab, of the 140 patients receiving the approved 2 mg/kg every three week dose, the overall response rate (ORR) (primary endpoint) for pembrolizumab was 33 percent in ipilimumab-naïve patients (95% CI, 21, 48) (n=51) and 25 percent in patients previously-treated with ipilimumab (95% CI, 16, 35) (n=89). The secondary endpoints were overall survival (OS), progression-free survival (PFS), and duration of response per RECIST v1.1. Results were similar across dosing schedules.
KEYNOTE-002 is a Phase 2, multi-center, randomized study of pembrolizumab (2 mg/kg every three weeks or 10 mg/kg every three weeks) compared to investigator-choice chemotherapy in 540 patients with advanced melanoma who were previously-treated with ipilimumab and, if BRAF V600 mutation positive, a BRAF or MEK inhibitor. The primary endpoints were PFS and OS. Both pembrolizumab doses evaluated were superior compared to chemotherapy for PFS at both six-months and nine-months, with PFS rates of 34 and 24 percent, respectively, for the 2 mg/kg dose (95% CI, 0.57 [0.45, 0.73]) (n=180) and 38 and 29 percent for the 10 mg/kg dose (95% CI, 0.50 [0.39, 0.64]) (n=181), compared to 16 and 8 percent for investigator-choice chemotherapy (n=179). OS data were not mature at the time of the analysis. The secondary endpoints were ORR and duration of response per RECIST v1.1.
KEYNOTE-006 is a Phase 3, multi-center, randomized, study of pembrolizumab (10 mg/kg every two or three weeks) compared to ipilimumab in 834 patients with advanced melanoma. In the planned interim analysis of the co-primary endpoints, pembrolizumab demonstrated superior PFS and OS compared to ipilimumab. The estimated 6-month and 9-month PFS rates for pembrolizumab were 47 and 40 percent, respectively, for the 2-week group (95% CI, 0.58 [0.46, 0.72], p<0.00001) (n=279) and 46 and 42 percent for the 3-week group (95% CI, 0.58 [0.47, 0.72], p<0.00001) (n=277), compared to 27 and 16 percent for ipilimumab (n=278). One-year OS for pembrolizumab was 74 percent (2-week group) (95% CI, 0.63 [0.47, 0.83], p = 0.00052) and 68 percent (3-week group) (95% CI, 0.69 [0.52, 0.90], p = 0.00358), compared to 58 percent for ipilimumab. The risk of death was reduced by 31 percent for patients treated with pembrolizumab in the 3-week group (hazard ratio 0.69) and 37 percent in the 2-week group (hazard ratio 0.63). The secondary endpoints were ORR and duration of response per RECIST v1.1.
The safety analysis supporting the European approval of pembrolizumab was based on 1,012 advanced melanoma patients across three doses (2 mg/kg every three weeks or 10 mg/kg every two or three weeks) in studies KEYNOTE-001 and KEYNOTE-002 combined. The most common adverse reactions (>10%) with pembrolizumab were diarrhea (15%), nausea (12%), pruritus (25%), rash (25%), arthralgia (13%) and fatigue (33%). The majority of adverse reactions reported were of Grade 1 or 2 severity. The most serious adverse reactions were immune-related adverse reactions and severe infusion-related reactions.
Melanoma, the most serious form of skin cancer, is characterized by the uncontrolled growth of pigment-producing cells. The incidence of melanoma has been increasing over the past four decades. In Europe, approximately 100,000 new cases were estimated to be diagnosed in 2012, which is almost half of the global incidence of melanoma. The five-year survival rates for advanced or metastatic melanoma (Stage IV) are estimated to be 15 to 20 percent in the United States and 5 to 22 percent in Europe.
Pembrolizumab is a humanized monoclonal antibody that blocks the interaction between PD-1 and its ligands, PD-L1 and PD-L2. By binding to the PD-1 receptor and blocking the interaction with the receptor ligands, pembrolizumab releases the PD-1 pathway-mediated inhibition of the immune response, including the anti-tumor immune response.
With the European Commission decision, pembrolizumab is now approved in more than 35 countries for the treatment of advanced melanoma. MSD is advancing a broad and fast-growing clinical development program for pembrolizumab with more than 100 clinical trials – across more than 30 tumor types and enrolling more than 16,000 patients – both as a monotherapy and in combination with other therapies.
Our Focus on Cancer
Our goal is to translate breakthrough science into innovative oncology medicines to help people with cancer worldwide. At MSD Oncology, helping people fight cancer is our passion and supporting accessibility to our cancer medicines is our commitment. Our focus is on pursuing research in immuno-oncology and we are accelerating every step in the journey – from lab to clinic – to potentially bring new hope to people with cancer.
Today's MSD is a global healthcare leader working to help the world be well. MSD is a tradename of Merck & Co., Inc., with headquarters in Kenilworth, N.J., U.S.A. Through our prescription medicines, vaccines, biologic therapies and animal health products, we work with customers and operate in more than 140 countries to deliver innovative health solutions. We also demonstrate our commitment to increasing access to healthcare through far-reaching policies, programs and partnerships.
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