Three biopharma drugs are up for FDA approval this week, including one new chemical entity, dasotraline, from Sunovion Pharmaceuticals Inc. to treat binge eating disorder, and two other candidates that are part of supplemental filings for expanded indications.
Sunovion’s drug and Blueprint Medicines Corp.’s Ayvakit (avapritinib) to treat fourth-line gastrointestinal stromal tumors (GIST) have PDUFA dates set for May 14, while Clovis Oncology Inc.’s Rubraca (rucaparib) for prostate cancer is scheduled for May 15.
The FDA accepted Marlborough, Mass.-based Sunovion’s new drug application in July 2019 for its moderate to severe binge eating disorder drug, dasotraline, a dopamine and norepinephrine reuptake inhibitor. The once-daily drug demonstrated efficacy in two 12-week, randomized, placebo-controlled studies, and was found to be generally well-tolerated.
In the SEP360-321 study, the higher 6-mg/day dose decreased the number of binge days per week from baseline compared to placebo, while the lower 4-mg/day dose did not meet the primary endpoint. Both doses, however, were better than placebo on the Binge Eating Clinical Global Impression-Severity (BE-CGI-S) score and the Yale-Brown Obsessive Compulsive Scale Modified for Binge Eating (Y-BOCS-BE) total score. An earlier pivotal study, SEP360-221, of dasotraline 4 mg-8 mg/day showed statistically significant improvement over placebo in the number of binge days per week, as well as with the BE-CGI-S score and the Y-BOCS-BE total score.
Binge eating disorder is often associated with other mental health conditions such as depression, substance abuse and post-traumatic stress disorder. It involves the consumption of large quantities of food in short periods of time, resulting in intense feelings of shame and guilt and a number of medical complications that affect quality of life. Dasotraline was previously under FDA review for attention deficit hyperactivity disorder, but Sunovion received a complete response letter in August 2018 asking for additional clinical data.
Drugs on Deck for this week also include Cambridge, Mass.-based Blueprint’s Ayvakit to treat fourth-line GIST. The FDA approved the candidate in January for adults with unresectable or metastatic GIST harboring a PDGFRA exon 18 mutation, but the agency was waiting on top-line data from the Voyager trial before making a decision on fourth-line GIST. Those data in third- and fourth-line patients emerged in late April showing Ayvakit did not meet the primary endpoint of improved progression-free survival (PFS) in comparison with regorafenib (Stivarga, Bayer AG). Specifically, those receiving Ayvakit demonstrated a median PFS of 4.2 months vs. regorafenib’s 5.6 months.
As a result, Blueprint said it was discontinuing further development of all GIST indications beyond PDGFRA exon 18 mutant GIST, including PDGFRA D842V mutations, which represent about 6% of newly diagnosed patients. Nevertheless, a decision on fourth-line GIST is expected by the FDA’s PDUFA action date of May 14, according to Blueprint’s May 6 10-Q filing with the SEC. Avapritinib has breakthrough therapy designation for unresectable or metastatic GIST with the PDGFRA D842V mutation, as well as orphan drug and fast track designation, from the FDA.
Competitor Deciphera Pharmaceuticals Inc.’s ripretinib for advanced GIST in patients previously treated with imatinib, sunitinib and regorafenib has priority review and a PDUFA date of Aug. 13. Blueprint’s failed Voyager trial resulted in its shares dropping by 17%, while Waltham, Mass.-based Deciphera’s rose by 16%, on April 28.
Boulder, Colo.-based Clovis also is awaiting FDA news by May 15 on its supplemental NDA for Rubraca, a PARP inhibitor, to treat BRCA1/2-mutant recurrent, metastatic castrate-resistant prostate cancer. The sNDA was filed in November 2019 and has priority review status with data from the Triton clinical program. Clovis is preparing for a virtual-only launch. Rubraca was first approved in December 2016 under an accelerated pathway for advanced ovarian cancer.
Finally, Cambridge, U.K.-based Astrazeneca plc’s PARP inhibitor, Lynparza (olaparib), was up for two potential FDA approvals in the second quarter, but one was granted May 8 for its use as a maintenance treatment with bevacizumab (Avastin, Genentech Inc.) for advanced ovarian cancer. Lynparza remains under priority review for metastatic castration-resistant prostate cancer. It is partnered with Kenilworth, N.J.-based Merck & Co. Inc.
On April 24, the partners announced further phase III Profound results showing a statistically significant and clinically meaningful improvement in the secondary endpoint of overall survival with Lynparza vs. enzalutamide or abiraterone in men with BRCA1/2 or ATM gene mutations. The trial had already met the primary endpoint in August 2019, demonstrating significantly improved radiographic PFS.