FDA approves Merck & Co.'s PD-1 inhibitor Keytruda for advanced or unresectable melanoma

The FDA announced Thursday that Merck & Co.'s Keytruda (pembrolizumab) was granted accelerated approval for advanced or unresectable melanoma, making it the first PD-1 inhibitor cleared in the US. Specifically, the agency said the therapy is intended for patients after they have received treatment with Bristol-Myers Squibb's Yervoy (ipilimumab), while for patients who carry the BRAF V600 mutation, Keytruda is indicated following treatment with Yervoy and a BRAF inhibitor. Merck stated that the drug would be available on the US market within one week.

The company said the decision was based on data from the ongoing Phase Ib KEYNOTE-001 study, which indicated that Keytruda was associated with an estimated overall survival (OS) rate of 69 percent at one year, while among patients previously treated with Yervoy the rate was 74 percent. In addition, results showed the estimated OS rate at 18 months to be 62 percent, while about 34 percent of patients overall displayed tumour shrinkage of at least 30 percent. Merck noted that it is conducting ongoing Phase II and Phase III studies in advanced melanoma designed to provide further confirmatory evidence for the drug.

Richard Pazdur, director of the Office of Hematology and Oncology Products in the FDA's Center for Drug Evaluation and Research, remarked that Keytruda, also known as MK-3475, "is the sixth new melanoma treatment approved since 2011, a result of promising advances in melanoma research." The therapy, which was also formerly known as lambrolizumab, had been granted breakthrough therapy status by the agency for the treatment of advanced melanoma in April 2013.

Merck initiated a rolling US regulatory submission process for the immunotherapy this past January in patients with advanced melanoma previously treated with Yervoy. Meanwhile, the drugmaker's European application for Keytruda in advanced melanoma was accepted in June. Analysts estimate that Keytruda could amass $1.5 billion in revenue by 2017, while Leerink is forecasting sales of $6 billion for the therapy by 2025. Merck has indicated that Keytruda would be priced at $12 500 per month, or $150 000 for a year's worth of treatment.

The drug is also being developed for a number of other indications, including lung cancer, advanced head and neck cancer, and late-stage bladder cancer. Last month, Merck and Pfizer disclosed an agreement to develop Keytruda in combination with the latter's lung cancer drug Xalkori (crizotinib) in a Phase Ib study of patients with ALK-positive advanced or metastatic non-small-cell lung cancer (NSCLC). Prior to that, Merck forged collaborations to investigate use of Keytruda as part of various combination regimens, including with Pfizer's Inlyta (axitinib) for renal cell carcinoma, with Amgen's investigational talimogene laherparepvec in patients with previously untreated advanced melanoma, and with Incyte's experimental immunotherapy agent INCB24360 for previously treated metastatic and recurrent NSCLC, among others.

Meanwhile, a number of other drugmakers, including Bristol-Myers Squibb, Roche and Novartis, are also developing PD-1 inhibitors for various cancer indications. In June, Bristol-Myers Squibb halted a Phase III study of its experimental PD-1 inhibitor nivolumab after an Independent Data Monitoring Committee found the drug extended OS compared to dacarbazine in certain patients with advanced melanoma, while earlier that month, the company reported positive Phase I data for nivolumab in combination with Yervoy for the treatment of advanced melanoma. Bristol-Myers Squibb and Ono Pharmaceutical launched nivolumab this week in Japan at a price of $143 000 for a year's worth of treatment per patient, and the therapy is expected to be reviewed by US regulators in the months ahead.

For related analysis, see ViewPoints: Japanese market provides mixed-sentiment reference points for price of forthcoming key drug launches and ViewPoints: Perlmutter's pipeline narrative continues to gain momentum at Merck & Co.

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