FDA Approves Merck's PD-1 Inhibitor, Keytruda
The FDA Office of Drug Information announced this afternoon the granting of accelerated approval to Keytruda (pembrolizumab; MK-3475),Merck's anti-PD-1 drug for advanced or unresected melanoma that no longer responds to other drugs.
Melanoma is a skin cancer originating in pigment-producing cells called melanocytes. The disease is particularly swift and deadly in cases where it metastasizes to other sites in the body, particularly the brain. About 76,000 people will be diagnosed with melanoma in the U.S. this year and nearly 10,000 will die.
FDA’s decision wasn’t expected until late October on the drug, a monoclonal antibody that inhibits the programmed death receptor-1 of activated T lymphocytes, blocking a major pathway by which cancer cells evade the immune system.
Forbes’ Matthew Herper has covered this class of drugs extensively, as well as other approaches to mobilize T-cells in fighting cancer. Update, September 5: Here is Herper’s take on the Keytruda approval in the context of other drugs in the pipeline and a perspective on safety and pre-approval compassionate use from Merck’s research director, Roger Perlmutter.
Keytruda is intended for use after ipilimumab (Yervoy; Bristol-Myers Squibb BMY -0.72%) which blocks another T-cell receptor called CTLA-4. In the event the patient’s melanoma expresses the V600E amino acid change in the BRAF cell signaling protein, Keytruda should be given only after ipilimumab and a BRAF inhibitor such as vermurafenib (Zelboraf; Genentech/Daiichi Sankyo ) or dabrafenib (Tafinlar; GSK).
Bristol-Myers Squibb received approval in Japan for their anti-PD-1 drug, Opdivo (nivolumab), leading to speculation that it might be the first to be approved in the U.S.
Peter Loftus of the Wall Street Journal has reported on concerns raised after BMS and their marketing partner in Japan, Ono Pharmaceutical, priced the drug there at an average annual cost equivalent to $143,000. One can likely expect Keytruda to come in at a similar cost here.
In Merck’s press release today, a trend can be seen as pharmaceutical companies increasingly express gratitude to research study participants:
“KEYTRUDA embodies Merck’s unwavering commitment to pursue breakthrough science to help people who are facing the most challenging diseases,” said Kenneth C. Frazier, chairman and chief executive officer, Merck. “We are grateful to the people with advanced melanoma who participated in our trials, and the scientific and medical community for the shared effort that has led to the accelerated approval of KEYTRUDA.”
In a 411-patient efficacy and safety presented in preliminary form in June at the American Society of Clinical Oncology meeting, not enough time had passed to gauge median overall survival, with 69% of patients alive after one year and an average progression-free survival time of 5.6 months. Stage 4 melanoma generally carries a 5-year survival rate of 10 to 15 percent, according to theAmerican Cancer Society , although many factors influence the long-term prognosis.
Accelerated approval is granted by the FDA for drugs targeting serious or life-threatening diseases where a surrogate marker of efficacy (e.g., progression-free survival) provides an indication that the drug is “reasonably likely” to benefit patients. As the agency’s statement notes today, “This program provides earlier patient access to promising new drugs while the company conducts confirmatory clinical trials.”
Compassionate use attention
But, for some, access isn’t early enough.
Anticancer drugs targeting the PD-1 receptor have been a hot topic among patients seeking pre-approval, compassionate access to therapies outside of clinical trials.
A 25-year-old California woman, Mikaela Knapp, died in late April as her husband and PR industry colleagues appealed to the three pharmaceutical companies developing this class of drugs (Roche & Genentech, in addition to Merck and BMS).
Most recently, a social media campaign, #4Nathalie, has targeted anti-PD-1 drug sponsors on behalf of Nathalie Traller, a 15-year-old with a rare pediatric cancer called, alveolar soft part sarcoma (ASPS), for which no traditional chemotherapy is effective.
Perhaps best-known, however, was the unsuccessful “Save Locky’s Dad”campaign by the family of Colorado’s Nick Auden for PD-1 immunotherapies. Mr. Auden passed away from stage 4 melanoma in November 2013.
The ethical and practical complications of such campaigns for the terminally-ill has led NYU’s Arthur Caplan and former Chimerix CEO, Kenneth Moch, to propose a national institutional review board for compassionate use requests.
Early detection is crucial to survival
While new therapies for advanced melanoma are certainly welcome, monitoring your skin – or that of a loved one – is key to early detection and sustainable cures. One of my old colleagues, University of Colorado medical oncologist, Dr. Bill Robinson, used to start his lectures saying that once a year, you should take a shower with your favorite friend and “examine each others’ pelt.”
Which of the ABCDE criteria below does this melanoma meet? Credit: National Cancer Institute
Dermatologists and primary care physicians should usually tell you about the ABCDE system for monitoring moles and birthmarks:
Asymmetry: One half of the abnormal area is different from the other half.
Borders: The edges of the growth are irregular.
Color: Color changes from one area to another, with shades of tan, brown, or black, and sometimes white, red, or blue. A mixture of colors may appear within one sore.
Diameter: The spot is usually (but not always) larger than 6 mm in diameter – about the size of a pencil eraser.
Evolution: The mole keeps changing appearance.
Another good idea these days is to take a smartphone photo of your moles with a ruler beside them and show any changes to your doctor.
This article has been updated since its original posting.
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