Despite evidence of efficacy in binge-eating disorder (BED), Sunovion Pharmaceuticals Inc.'s dasotraline's second lease on life is done, for now. Following an initial plan to discontinue the asset in a 2010 portfolio reshuffle, the drug is now being shelved due to the need for additional clinical studies on its benefit-risk profile, parent Sumitomo Dainippon Pharma Co. Ltd. said. NDAs for BED and attention deficit hyperactivity disorder (ADHD) were withdrawn amid growing competitive threats to dasotraline's indications from generics and Sumitomo Dainippon's increasing focus on innovative medicines.

"While Sunovion considers dasotraline to be a promising, novel treatment for BED and ADHD, we believe that further clinical studies would be needed to support a regulatory approval for dasotraline in these indications," the company said. Furthermore, with the only drug currently approved for BED, Takeda Pharmaceutical Co. Ltd.'s Vyvanse (lisdexamfetamine), poised to face generic competition soon and the necessity of getting past a complete response letter in ADHD, Sunovion's managers may have found the drug's prospects dimmer than once expected.

Despite those challenges, as recently as March 3, Sumitomo Dainippon's CEO and president, Hiroshi Nomura, had indicated the company would launch dasotraline for BED in the U.S. this year. What changed wasn't entirely clear, as Sunovion declined to make its CEO available for comment Wednesday.

The clinical case

A dual-acting dopamine and norepinephrine reuptake inhibitor, dasotraline has shown efficacy against moderate to severe BED in trials. In the SEP360-221 study, a 12-week, randomized phase II/III study, once-daily in doses of dasotraline ranging from 4 mg to 8 mg were tested against placebo. The primary efficacy endpoint was the change from baseline in number of binge days per week at week 12. Dasotraline was statistically superior to placebo on the primary efficacy endpoint and all key secondary efficacy endpoints and was generally well-tolerated, Sunovion said. The most common adverse events were consistent with completed adult dasotraline studies and included insomnia, dry mouth, decreased appetite, anxiety, nausea and decreased weight.

Another study, the phase III SEP360-321 trial, found that fixed, once-daily doses of dasotraline also met its primary efficacy endpoint, demonstrating a statistically significant decrease in the number of binge days per week at week 12 in the group treated with dasotraline 6 mg/day vs. a placebo-treated group.

Following the FDA's acceptance of Sunovion's NDA for the drug in moderate to severe BED in July 2019, the regulator set a May 14 PDUFA date.

Looking ahead

Sumitomo acquired Sunovion, then called Sepracor Inc., in 2009 for about $2.6 billion, a deal that at the time turned on Sepracor's insomnia drug, Lunesta (eszopiclone), and the schizophrenia drug Latuda (lurasidone), sales of which hit $1.69 billion in 2019 and are still climbing. In Sumitomo's most recent financial report, it said the U.S.-based company "continued to pour its resources into maximizing revenue" from Latuda and expanding sales of other mainstay products.

Meanwhile, despite dasotraline's demise, Marlborough, Mass.-based Sunovion's strategic direction for the future has not changed, representative Kristina Coppola told BioWorld, citing the advancement of SEP-363856, a non-dopamine 2 candidate for schizophrenia now in phase III testing. Additionally, Sunovion expects an FDA decision later this month regarding its resubmitted NDA for apomorphine sublingual film, a potential new treatment option for "off" episodes associated with Parkinson’s disease. In January 2019, the FDA issued a CRL requesting additional information and analyses, but no new clinical studies. Following acceptance of the resubmission in December 2019, the regulator assigned the application a May 21 PDUFA date.

An estimated 4.1 million people in the U.S. experience recurrent and persistent episodes of binge eating, according to statistics Sunovion shared last summer. For those looking for further treatment options beyond Vyvanse, Takeda has explored a new possibility, the bis-aryl-sulfanyl amine vortioxetine, a drug already approved as Trintellix for major depressive disorder. Initial data posted by the company to appears to suggest that for BED, it performed similarly to a placebo on the trial's primary endpoint, change in number of binge eating episodes.

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