AbbVie's Vraylar turns in mixed results in depression, but pharma decides to file for approval anyway

AbbVie
Despite the mixed data, AbbVie still plans to file Vraylar with the FDA for the adjunctive treatment of major depressive disorder in the first half of 2022, AbbVie President Mike Severino said. (AbbVie)

AbbVie’s antipsychotic Vraylar could get a major boost from a potential expansion into depression. But like some other late-stage contenders, the drug’s clinical results fell short of a home run.

Vraylar, used as an adjunctive treatment to existing antidepressants, significantly outdid placebo in a phase 3 trial, AbbVie unveiled Friday. But additional results are complicating the win.

A statistically significant improvement, as measured by a clinician-administered score called the Montgomery-Åsberg Depression Rating Scale (MADRS), was only seen with the drug at the 1.5 mg/day dose in one of two phase 3 Vraylar trials. In the other trial, that dose showed a numerical edge but missed the primary endpoint. The measurement in each trial was taken at six weeks.

In perhaps a more perplexing showing, MADRS improvement from the higher 3 mg/day Vraylar dose failed to cross the statistical significance bar in both trials.

RELATED: Axsome sees depression drug decision delayed as FDA kicks expected CRL can down the road

Despite the mixed data, AbbVie still plans to file Vraylar in the first half of 2022 with the FDA for the adjunctive treatment of major depressive disorder, AbbVie President Mike Severino said during the company’s third-quarter earnings call Friday.

Part of Severino’s argument rests on the drug showing “clear trends toward a clinically meaningful benefit” at both strengths at week four and six. Plus, in a phase 2/3 trial dubbed RGH-MD-75, patients treated with flexible Vraylar doses between 2 mg/day to 4.5 mg/day saw an improvement in MADRS scores over control.

“Based on precedents in the field and the totality of the data, we believe we have a viable regulatory pathway for Vraylar as adjunctive treatment for major depressive disorder,” Severino said.

Vraylar, which AbbVie got from its gigantic Allergan merger, is approved at different dosing regimens for schizophrenia and bipolar I disorder. The drug reeled in $461 million in third-quarter sales, up 29% year over year, making it the fastest-growing atypical antipsychotic, Jeff Stewart, AbbVie’s commercial chief, said during Friday’s call.

RELATED: Biogen-Sage depression drug hits main goal of improving symptoms, then it gets complicated

About half of major depressive disorder patients don’t achieve adequate control with frontline monotherapy agents, Severinoa noted during a previous call in July. That leaves a market for Vraylar that’s about the same size as the bipolar segment, Stewart added at the time.

In a March report, GlobalData projected that the major depressive disorder market will grow to $7.87 billion by 2029 across eight major markets. GlobalData analyst Philippa Salter at that time pegged Axsome Therapeutics’ AXS-05 as the most promising pipeline candidate. But the FDA in August found deficiencies in the company’s regulatory submission and has delayed a decision.

Biogen’s zuranolone also recently showed mixed results in a phase 3 trial, including missing some secondary goals and a quick ebb of efficacy on alleviating depression symptoms. Biogen paid Sage Therapeutics $1.5 billion upfront to license the drug.