Zuranolone cleared for post-partum depression, but not MDD

Biogen and Sage Therapeutics' zuranolone has become the first oral drug to be approved by the FDA for post-partum depression (PPD), but the US regulator turned down a request for wider use in the treatment of major depressive disorder (MDD).

The GABAA receptor positive allosteric modulator will be sold as Zurzuvae for PPD, which affects women after childbirth and can make it hard for new mothers to bond with their newborns. In extreme cases, it can lead to thoughts of harming themselves or their child.

Biogen and Sage confirmed, however, that they had received a complete response letter (CRL) from the FDA for the MDD indication, which said they had not provided "substantial evidence" of effectiveness in this larger patient population.

A launch will take place after a standard review by the Drug Enforcement Administration (DEA) to assess whether the drug will be regulated as a controlled substance, likely sometime in the fourth quarter of this year, said Biogen and Sage. No pricing information has been revealed as yet.

Biogen's chief executive, Chris Viehbacher, accentuated the positive with the news, noting that Zurzuvae is the first oral, fast-acting therapy for PPD and will be an option for "hundreds of thousands of women who experience this underdiagnosed and undertreated condition."

The once-daily pill provides an alternative to current therapies for PPD that have to be administered via intravenous infusion, said the FDA. In clinical trials, zuranolone was shown to start working in as little as three days - more quickly than current antidepressant therapies - with the effects maintained for at least four weeks after the final dose on day 14.

Biogen and Sage said that around one in eight women experience symptoms of PPD, around 500,000 per year, but only around 16% receive treatment, suggesting the companies may have their work cut out building a sustainable market for the drug.

There's no question, however, that failing to get the MDD indication on the label will hold back the sales potential for the drug, with analysts suggesting the PPD opportunity will be upwards of $500 million, while approval in MDD would unlock $1 billion-plus sales.

The companies said they were evaluating their next steps for the MDD programme, but it is possible a new study will be needed. The FDA's decision does not come as a complete surprise, as in MDD trials zuranolone was shown to have relatively modest efficacy, with some debate about the durability of its response.

The disappointment comes as Biogen is grappling with weaker sales of its multiple sclerosis franchise, R&D setbacks, and the misfire of Alzheimer's therapy Aduhelm (aducanumab), which have forced it to slash staff and look externally to boost its product range and pipeline.

The biotech has another couple of recent approvals under its belt that have improved its outlook, however, including Aduhelm follow-up Leqembi (lecanemab), partnered with Eisai, and Qalsody (tofersen) for a rare form of amyotrophic lateral sclerosis (ALS).

Image by Daniel Nebreda from Pixabay.