The FDA has started its review of Alkermes’ experimental antipsychotic for schizophrenia and bipolar I disorder – ALKS 3831 – setting up a possible approval in November.
ALKS 3831 combines the established oral antipsychotic olanzapine – originally developed and sold by Eli Lilly as Zyprexa but now generically available – with samidorphan, a mu-opioid receptor antagonist designed to counteract olanzapine-associated weight gain.
Dublin-based Alkermes filed for approval of the drug in the US last November, and the FDA has said it expects to make its decision on the drug by 15 November.
Olanzapine is an effective and well-established antipsychotic treatment option for patients with schizophrenia and bipolar, but its clinical use has always been limited by a high risk of weight gain, which results from appetite stimulation.
The increased weight not only heightens patients’ risk of cardiovascular disease, but also reduces their quality of life and can lead to poor compliance with treatment.
The filing of ALKS 3831 is based on two phase 3 studies – ENLIGHTEN-1 and ENLIGHTEN-2 – which showed respectively that Alkermes drug was as effective as olanzapine on its own at controlling schizophrenia symptoms, and that it did so while reducing weight gain.
In ENLIGHTEN-2, patients taking ALKS 3831 had a lower average percent weight gain from enrolment after six months compared with olanzapine, and fewer of them reached the threshold of a 7% increase at that time point.
It’s another stop on the road to recovery for Alkermes, which suffered a major setback last year when the US regulator rejected its antidepressant candidate ALKS-5461 – based on samidorphan and buprenorphine – saying that there wasn’t enough evidence to show it was clinically effective.
The project has since been dropped, and its demise prompted a wave of job cuts at the loss-making biotech later in 2019 in an effort to slash $150m off its annual costs.
That left Alkermes more reliant on a positive outcome for ALKS 3831, its other late-stage development prospect. Shortly after, it agreed a $950m deal to buy Rodin Therapeutics and expand its pipeline with a series of early-stage candidates for synaptopathies such as Alzheimer’s, Parkinson’s and Huntington’s disease.
There have been problems for its already-marketed drugs too, notably an FDA warning letter about misbranding of its addiction therapy Vivitrol (naltrexone) in a print advert.
EvaluatePharma has previously predicted that sales of ALKS 381 could reach $381m in 2024 if approved, which would be a sizeable addition to its current revenues, expected to reach a little over $1.1bn in 2019.