LONDON—Taking a lead in the tight race to develop and release melanoma medications, GlaxoSmithKline plc (GSK) has received accelerated approval from the U.S. Food and Drug Administration for its combination of Mekinist (trametinib) and Tafinlar (dabrafenib) for treatment of melanoma with BRAF mutations V600E and V600K. Roche, which is also a big player in this market, is now behind, said Aine Slowey, senior analyst for London-based analysis firm Datamonitor Healthcare. While both GSK drugs had been approved as monotherapies in 2013, the combined results “were very positive and significantly better than the BRAF monotherapy,” Slowey said.
The Swiss giant has a monotherapy in Zelboraf (vemurafenib) but does not yet have a combination therapy targeting BRAF mutations. In fact, “the combination of Zelboraf and Yervoy has already crashed and burned,” she said. While Zelboraf is less toxic than Bristol-Myers Squibb’s (BMS) Yervoy (ipilimumab) and therefore may be used first, with Yervoy going only to those who see no improvement, a combination of the two drugs was hoped to be a powerful one-two punch. But the trial combining them was halted last year because of toxicity.
In the wake of that failure, Roche may be looking to “leapfrog” GSK, to combine dual therapy with additional PD-1 inhibitors, she said.
Both GSK’s approved dual treatment and the failed combination from Roche and BMS inhibit MEK as well as BRAF, delaying medication resistance that arose when inhibiting just BRAF. But it’s only a delay, Slowey said; eventually resistance does develop. Adding immunotherapy, such as PD-1 inhibition, may help, Slowey said.
Melanoma medications are a small, and relatively new, market. The disease is easily detected in its early stages, and surgery is usually both quick and effective, particularly when compared to surgery for other types of cancer. But basic research uncovered the fact that BRAF mutations are a “convenient biomarker that patients are going to respond well to this kind of targeted therapy,” Slowey said, so companies started exploring commercialization.
For those patients who do develop metastatic melanoma, about half have a BRAF V600 mutation; of those, 90 percent have the V600E variant, Slowey said. (The other half, who have what is called “wild-type” metastatic melanoma, get Yervoy and immunotherapy, Slowey said.)
While Datamonitor projects patient numbers will grow about 3.5 percent a year through 2021, the market numbers are still low: Seven years from now, there will only be 170,000 patients in the U.S., Japanese and European markets combined, the company projects, with sales totaling $459 million then.
Nevertheless, “it’s probably one of the fastest-moving oncology markets at the minute,” Slowey said.
Prior to 2011, only standard cytotoxic chemotherapies were available. But then Yervoy was approved for metastatic melanoma patients. Already there are four approved drugs, with more on the way.
BMS has entered the fray, winning fast-track designation for nivolumab, which is now in Phase 1 trials, as well as combination testing.