During the last week or so, both Bristol-Myers Squibb (NYSE:BMY) and Merck (NYSE:MRK) have announced delays in Food and Drug Administration decisions on approvals for their immuno-oncology drugs to treat melanoma. A decision on whether to expand the approval of Bristol-Myers Squibb's Opdivo to early-stage melanoma patients was pushed back from August 27 to November 27. And the FDA's goal to make a decision on the use of Merck's Keytruda in melanoma patients who no longer responded to Bristol's Yervoy is now scheduled for December 24.
The day after Thanksgiving and the day before Christmas. Coincidence? Absolutely.
The FDA automatically gives itself an extra three months to make a decision on a marketing application if the drugmaker submits additional information to supplement the initial application. That's only fair.
In Bristol-Myers Squibb's case, the company submitted additional information that showed the drug works irrespective of whether the tumor contains a mutation in a gene called BRAF. The initial application only included data from a trial that showed advanced melanoma patients with normal BRAF increased survival compared to dacarbazine chemotherapy. Sure the approval for patients with normal BRAF is delayed by three months, but the additional data should result in an earlier approval for patients with mutated BRAF than if the data was submitted in a separate supplemental application, which would have taken at least six months to be ruled on.
Merck was a little coyer about what exactly it submitted to cause the FDA to deem the addition a major amendment worthy of an automatic addition to the review time. "In an effort to provide the FDA with the most robust data for Keytruda in this population, Merck submitted an additional analysis from KEYNOTE-002," the press release said. KEYNOTE-002 was a phase 2 study that compared Keytruda to chemotherapy in patients that no longer responded to Yervoy.
Neither delay is that big of a deal
Bristol-Myers Squibb has also submitted an application to get Opdivo approved in combination with Yervoy, which it also sells, in patients with previously untreated advanced melanoma. The FDA is scheduled to make a decision on that application by September 30.
In a phase 3 trial comparing Opdivo plus Yervoy to the two drugs as monotherapies, the combination delayed progression or death by 11.5 months. Opdivo alone delayed progression or death by 6.9 months, while Yervoy alone only delayed progression by 2.9 months. Getting Opdivo approved as a monotherapy may not be all that important if most patients are going to be treated with the combination of Opdivo and Yervoy.
Merck has already submitted an application to use Keytruda as a first-line treatment for melanoma patients. The FDA is scheduled to make a decision about that application on or before December 19, so the agency could actually approve the drug as a first-line treatment a few days before it makes a decision about the drugs' use as a later-line treatment.
It seems likely -- or at least logical, if that's possible for a government agency -- that the FDA will hand down both decisions at the same time. The oncology division at the FDA has been consistently making decisions well ahead of its target action dates, so we could see decisions for Opdivo and Keytruda ahead of the dates listed above.
In the meantime, both drugs are already on the market, so even though they're not approved for late-stage melanoma patients, they're being prescribed off label for those patients.