On the 9th of October, Alkermes announced positive voting from the joint meeting of the FDA’s Psychopharmacologic Drugs Advisory Committee (PDAC) and the Drug Safety and Risk Management Advisory Committee (DSRM), in support of its pipeline candidate ALKS-3831 (samidorphan with olanzapine) for the treatment of schizophrenia and bipolar I disorder.

The development of drugs with enhanced safety profiles has been a consistent unmet need within schizophrenia. The most notable side effects caused by current treatments are metabolic effects, such as weight gain and extrapyramidal symptoms (EPS). Metabolic syndrome is the most challenging aspect in the management of schizophrenic patients. This is further compounded by the fact that, compared to other side effects caused by current therapies, metabolic abnormalities are much more difficult to treat or reverse, especially in the long term.

Alkermes’ ALKS-3831 is a novel, fixed-dose combination (FDC) drug composed of samidorphan, a μ-opioid receptor antagonist, and the established atypical antipsychotic, olanzapine (generic Zyprexa). Olanzapine is one of the most frequently prescribed antipsychotics for the treatment of schizophrenia; however, one of the major issues surrounding olanzapine as a monotherapy is its metabolic side effects in patients, particularly weight gain. Alkermes’ candidate aims to negate the metabolic abnormalities associated with current treatments for schizophrenia.

During the Phase III ENLIGHTEN-1 and ENLIGHTEN-2 clinical trials of ALKS-3831, Alkermes primarily studied patients with schizophrenia. Alongside the schizophrenia data, the company submitted pharmacokinetic bridging data comparing ALKS-3831 to olanzapine in patients with bipolar I disorder as part of its new drug application (NDA). ALKS-3831 has a Prescription Drug User Fee Act (PDUFA) date of 15 November 2020. If the drug gains FDA approval for schizophrenia, it is likely to also gain approval for the bipolar indication as olanzapine is already used in the treatment of the latter indication.

According to GlobalData’s primary research with key opinion leaders (KOLs), if ALKS-3831 is approved, several olanzapine prescribers would attempt to switch their patients to ALKS-3831, when possible. That said, payer barriers such as stringent prior authorization and copayment requirements could dramatically reduce the drug’s actual market uptake. Nonetheless, Alkermes is expected to play a greater role in the schizophrenia market and with ALKS-3831, the company will be able to expand its presence in this market. ALKS-3831 could position itself as a first-line therapy in the treatment paradigm for schizophrenia. GlobalData forecasts ALKS-3831 peak sales of $364M in 2026.