The phase III failure of Blueprint Medicines Corp.’s avapritinib to meet its primary endpoint of improving progression-free survival (PFS) in patients with locally advanced unresectable or metastatic gastrointestinal stromal tumors (GIST) pummeled the company stock on Tuesday but boosted shares and hopes at Deciphera Pharmaceuticals Inc.
Deciphera’s NDA for ripretinib in treating advanced GIST in patients who have received prior treatment with imatinib, sunitinib and regorafenib was accepted for priority review by the FDA and has a PDUFA date of Aug. 13. Deciphera also has the INTRIGUE pivotal phase III study of ripretinib in second-line GIST underway. The company expects complete enrollment in the second half of 2020.
Blueprint’s stock (NASDAQ:BPMC) closed 17.31% down Tuesday, at $58.63 per share, while Deciphera (NASDAQ:DCPH) shares shot 16.12% upward to close at $56.20.
Despite the phase III failure, Cowen analyst Marc Frahm wrote Tuesday that he still views Blueprint shares as undervalued as he expects avapritinib to be “used broadly” in growth factor receptor alpha (PDGFRa) patients, plus possibly used off-label in the future. He pins the drug’s strength to its “strong” clinical profile, the lack of available treatment options for those patients and the large market size.
Last summer, Deciphera disclosed positive data from a pivotal phase III study showing that ripretinib, its lead candidate, a broad-spectrum KIT and platelet-derived PDGFRa inhibitor, enabled people with fourth-line disease and beyond to live a median of 6.3 months before disease progression vs. one month with placebo. Ripretinib also reduced the risk of disease progression or death by 85%. On a key secondary endpoint of the trial, called Invictus, ripretinib demonstrated an overall response rate (ORR) of 9.4% compared with 0% for placebo (p=0.0504), though that result was not statistically significant. In December, Deciphera submitted an NDA for ripretinib in GIST patients who have received a prior treatment with imatinib (Gleevec, Novartis AG), sunitinib (Sutent, Pfizer Inc.) and Stivarga.
Blueprint’s failed phase III VOYAGER trial evaluated the efficacy and safety of avapritinib (N=240) vs. regorafenib (N=236) in patients with third- or fourth-line GIST, resulting in a median PFS of 4.2 months compared to 5.6 months for regorafenib. The difference in median PFS between the avapritinib and regorafenib groups was not statistically significant, the company said. The ORR was 17% for the avapritinib group and 7% for the regorafenib group. Avapritinib was generally well-tolerated with most adverse events reported as grade 1 or 2. Top-line safety results were consistent with previously reported data and no new safety signals were observed, the company added.
GIST is a rare, genomically driven sarcoma of the gastrointestinal tract. About 6% of patients with newly diagnosed GIST bear PDGFRa exon 18 mutations, the most common being that of D842V, making the cancer resistant to all other approved therapies. For example, a retrospective study showed that when such patients were treated with Gleevec, they reaped an overall response rate of zero.
Blueprint said it will discontinue developing avapritinib for in non-PDGFRa exon 18-mutant GIST indications. Branded Ayvakit, the kinase inhibitor was approved by the FDA in January for treating adults with unresectable or metastatic gastrointestinal stromal tumors harboring a PDGFRa exon 18 mutation, including PDGFRa D842V mutations.
In Tuesday morning’s conference call with investors, Blueprint’s CEO and president, Jeff Albers, said the failure maintained the company’s financial runway into the second half of 2022 and reinforced its priorities as the company plans to continue to commercialize Ayvakit in the U.S and seek marketing approval for the drug elsewhere around the world. Blueprint is awaiting a decision from the European Commission on its marketing authorization application for treating adults with PDGFRa D842V-mutant GIST in the third quarter of 2020.
As of Dec. 31, 2019, Blueprint had cash, cash equivalents and investments of $548 million and had received $308.4 million in estimated net proceeds from its January 2020 follow-on public offering.