Biogen, Sage prep 2022 filing for depression drug zuranolone

The renaissance of Biogen and Sage Therapeutics antidepressant zuranolone continues, with the companies indicating they now plan to start a rolling submission for the drug early next year.

Two years ago things were looking bleak for zuranolone after the oral GABAA receptor modulator failed the phase 3 MOUNTAIN trial in major depressive disorder (MDD), raising questions about the future of the programme.

Earlier this year however Sage and Biogen reported more encouraging data in a second phase 3 trial – called WATERFALL – which showed that a two-week course of zuranolone significantly reduced symptoms of depression compared to placebo, with a rapid onset of action that started to be seen within three days.

Now, after discussions with the FDA, the two companies have said they are confident that the current data package is strong enough to move forward with filings in MDD in the second half of 2022, and in postpartum depression (PPD) the following year.

"The FDA's response on the regulatory pathway for zuranolone continued to be consistent with previous discussions," said Sage's chief executive Barry Greene.

"In the clinical development programmes, zuranolone has shown remarkably consistent, rapid, and sustained reductions in depressive symptoms, including anxiety and sleep loss, in addition to a well-tolerated safety profile," he added.

There had been speculation that the current dataset may not be sufficient to support approval, particularly as in WATERFALL there seemed to be a falloff in efficacy over the two-week follow-up period.

Sage and Biogen have previously said they will wait for the outcome of another study called CORAL – looking at zuranolone as an add-on to current antidepressant therapy – before filing the drug to the FDA for MDD.

That data is now due in early 2022, a little later than expected, and they are also holding off on a PPD submission until they complete the PPD 301-SKYLARK trial, due in 2023.

Biogen has a lot riding on zuranolone, having stumped up $1.525 billion upfront for rights to the drug and another Sage candidate for neurological diseases last year.

At the time the expectation was that Biogen was likely to fail to secure approval for its Alzheimer's drug Aduhelm (aducanumab), which was controversially given a green light in the US in June but has failed to make much impact in the market so far amid healthcare system and payer pushback.

It has also suffered a number of setbacks in its late-stage pipeline, most recently a failed phase 3 trial for  amyotrophic lateral sclerosis (ALS) hope tofersen.