- Allergan's experimental depression drug rapastinel failed to show a significant benefit in three late-stage studies, and looks set to miss its goal in a fourth, the company disclosed late Wednesday.
- The news marks a setback for Allergan's plans to recharge its portfolio of medicines for central nervous system disorders and comes at a precarious moment for the drugmaker. Shares in the company have steadily fallen since last October, spurring new calls for changes in the company's top ranks.
- "Deeply disappointed that our work on rapastinel will not lead to a new treatment option for patients with major depression, but we remain committed to R&D to combat mental illness," Allergan CEO Brent Saunders wrote on Twitter.
Clinical trials in depression are notoriously difficult, bedeviled by high placebo responses and a biology that's resisted definitive answers. Still, the topline results Allergan disclosed leave little room for silver linings.
Across three acute studies in which rapastinel was given together with an antidepressant, Allergan's drug did not differentiate from placebo. An interim analysis of a relapse prevention study revealed rapastinel is likely to miss its primary and secondary goals there as well.
Allergan said current Phase 3 testing of the drug as a monotherapy would continue, but acknowledged it expected to make a decision on those programs this year.
Wall Street expectations for the studies' chances of success were mixed, but analysts largely saw rapastinel as important for building confidence in Allergan's pipeline as well as in its broader ambitions.
Notably, rapastinel was once counted among a slate of six franchises that Allergan touted as future revenue drivers. Another drug in that group, Esmya (ulipristal) for uterine fibroids, was rejected by the Food and Drug Administration in August of last year.
Clinical setbacks have dimmed prospects for programs Allergan once called its "six stars"
|Rapastinel||Major depressive disorder||Failed three adjunctive studies|
|Esmya||Uterine fibroids||Rejected by FDA in Aug. 2018|
|Ubrogepant/atogepant||Migraine||Ubrogepant filing expected Q1|
|Cenicriviroc||NASH*||Phase 3 results expected in 2020|
|Abicipar||AMD/DME**||Filing expected in AMD in H1|
|Relamorelin||Gastroparesis||Phase 3 results expected in 2020|
*Non-alcoholic steatohepatisis **Age-related macular degeneration/diabetic macular edema SOURCE: Company
"We expect that another pipeline failure will increase investor frustration with the management team and could lead to greater investor activism ahead of the May 1 Annual Meeting," wrote Vamil Divan, an analyst at Credit Suisse, in a March 6 note to clients.
That frustration has bubbled up recently, spurring activist investor Appaloosa to urge Allergan shareholders to vote for a proposal requiring an independent board chairman. Allergan's Saunders currently serves as chair as well as company CEO.
Notably, Appaloosa's president David Tepper criticized the company in a shareholder letter for a "failed acquisition strategy resulting in an underperforming product pipeline."
Rapastinel's setback will add to Appaloosa's list. Allergan acquired the drug in a 2015 deal to buy Naurex for $560 million net of cash.
Allergan's announcement of rapastinel's clinical failures also come one day after Johnson & Johnson secured U.S. approval for Spravato (esketamine) in treatment-resistant depression. While the drugs work differently, both act on the NMDA receptor and were sometimes highlighted together by analysts as rapid-acting anti-depressants.
Shares in Allergan fell by 2.5% in post-market trading Wednesday.