Sage soars on postpartum depression data

Sage Therapeutics has scored a big win with postpartum depression (PPD) drug SAGE-217, after rolling the dice on an upgraded clinical trial last summer.

The pivotal data – reported at this week’s JP Morgan Healthcare conference in San Francisco – sparked a 40%-plus increase in Sage’s share price as investors responded to the news that it may be able to move ahead quickly with filing a second PPD drug.

Sage is already waiting for the FDA to complete its review of GABA_A modulator Zulresso (brexanolone), which is given as a 60-hour intravenous infusion and is intended to treat severe, acute cases of depression in hospital. If approved by the March 19 action date – which seems likely after an advisory committee voted overwhelmingly in favour of the drug last November – it will be the first drug specifically indicated for PPD in the US.

SAGE-217 has the same mechanism of action but can be given orally, potentially making it suitable for a much broader patient population. It has already picked up a breakthrough designation from the FDA, and last June the FDA confirmed Sage could file for PPD on the strength of a single phase II trial – the first time that this expedited route had been made available for an antidepressant.

The up-rating of the 151-patient ROBIN trial to phase III status was something of a gamble, but paid off for SAGE at the JPM meeting with the drug showing a “rapid, profound and sustained” reduction in symptoms of depression compared to placebo, according to the company.

After two weeks of outpatient treatment, SAGE-217-treated women had an almost 18-point improvement on the widely-used Hamilton Depression Rating Scale (HAM-D), while those on placebo showed a 13.6% increase. Moreover, at the end of the treatment 45% of women on Sage’s drug were in remission, compared to 23% of the placebo arm.

It’s that rapidity of onset that is generating the excitement about both Zulresso and SAGE-217, as the current antidepressant armamentarium can take weeks or even months to start working. Importantly, there were no reports of fainting (syncope) in ROBIN, alleviating earlier concerns that this could be an issue with the drug.

It is estimated that PPD affects approximately one in nine women who have given birth in the US – equivalent to around 400,000 women a year – and in severe cases can raise the risk of suicide or even harm to the baby.

The new data has reignited speculation that a larger company may decide the time is right to buy into Sage’s pipeline. The company featured high on a list of potential takeover targets in the US biotech sector published a year ago.

SAGE-217 is also in development for major depressive disorder (MDD), which would open up an even larger potential market, and according to analysts could catapult sales to blockbuster status, with Zulresso also making a contribution of a few hundred million dollars a year.

T-Positive results from a phase II trial in MDD were reported last year, and a phase III study is now ongoing with topline data due in 2020.