European Commission Approves Merck’s Keytruda

Merck announced on July 22, 2015 that the European Commission approved Keytruda (pembrolizumab), the company’s anti-PD-1 therapy, for the treatment of unresectable or metastatic melanoma in adults. The approval comes one day after the agency’s approval of Bristol-Myers Squibb’s Opdivo (nivolumab), which BMS said was the first PD-1 checkpoint inhibitor approved in Europe.

FDA approved Keytruda for the treatment of melanoma in September 2014, and it was the sixth new melanoma treatment approved by the agency since 2011. In October 2014, Keytruda also received a Breakthrough Therapy designation from FDA for the treatment of non-small cell lung cancer. Keytruda was also said to show "encouraging anti-tumor activity" in a trial for PD-L1-positive, advanced triple-negative breast cancer.

According to Merck, Keytruda received European Commission regulatory approval based on Phase III data showing "it is the first and only anti-PD-1 therapy to provide a statistically superior survival benefit as a monotherapy compared [with] ipilimumab, the current standard of care for advanced melanoma." FDA has said that Opdivo, however, which was approved in December 2014 and was the seventh melanoma treatment approved since 2011, offered substantial improvement over available therapies, including Keytruda (pembrolizumab), ipilimumab, peginterferon alfa-2b, vemurafenib, dabrafenib, and trametinib.

The overall response rate for Keytruda was 33% in ipilimumab-naïve patients and 25% in patients previously treated with ipilimumab. This response rate is similar to Opdivo’s response rate, which was 32%. The key to this puzzle may be first-line treatment with ipilimumab: As FDA points out, “Opdivo is intended for patients who have been previously treated with ipilimumab and, for melanoma patients whose tumors express a gene mutation called BRAF V600, for use after treatment with ipilimumab and a BRAF inhibitor.” In short, Keytruda’s response rate appears to be 1% higher than Opdivo’s, but upon further investigation, for patients previously treated with ipilimumab, Opdivo’s response rate is actually seven percentage points higher than Keytruda’s. Regardless of how they compare with one another, based on tumor shrinkage, it’s clear that both Opdivo and Keytruda are superior to BMS’ ipilumumab, which also goes by brand name Yervoy.

BMS and Ono Pharmaceutical are investigating the activity of the combination regimen of checkpoint inhibitors Opdivo and Yervoy in treatment-naïve patients in the ongoing trial dubbed CheckMate-067. In CheckMate-067, the one-year overall survival rate for patients with advanced melanoma was 94% and the two-year overall survival rate was 88%. In addition, in the CheckMate-067 study, both the Opdivo plus Yervoy regimen and the Opdivo as monotherapy regimen demonstrated higher objective response rates (57.6% and 43.7%, respectively) compared with Yervoy alone (19%).