Small Clinical Trials Lead To Big Results

By Rob Wright, Chief Editor, Life Science Leader
Follow Me On Twitter @RfwrightLSL

At the same time Sage Therapeutics was investigating its lead compound brexanolone for SRSE (super refractory status epilepticus), it also was assessing the drug as a use for PPD (postpartum depression). The approach taken with the SRSE study (i.e., going from open label to an immediate Phase 3) was not how the company had been approaching all of its other studies. “With PPD, for example, we started with four patients, and all four got dramatically better,” Jonas explains. This gave Sage enough information about the behavior of the potential molecule to design an efficient Phase 2 study, this time with 21 patients (still a small sample size compared to traditional Phase 2 studies). Data from this study showed that remission from depression, measured at 60 hours, was seen in seven of 10 of the brexanolone group compared with one of 11 in the placebo group. The results were being called one of the most important clinical findings in the pharmacologic treatment of PPD, and the drug’s rapid onset of action being unlike anything else available.

Though the brexanolone study was small, the data was strong enough for the FDA to grant a Breakthrough Therapy Designation (BTD). But Jonas notes the results also provided the team with enough information to do “design-efficient” Phase 3 studies. For example, the Phase 3 study 202B (patients with severe PPD) consisted of 122 patients, while study 202C (patients with moderate PPD) consisted of 104 patients. Positive results from these were announced on November 9, 2017, and represent the first Phase 3 program ever conducted in women with PPD. The company’s stock responded just as positively, rocketing up 54 percent from the previous day’s close of $62.66/share.

The company took a similar approach when testing one of its other compounds — SAGE-217 for major depressive disorder (MDD). “Here, again, we started with an open-label program that gave us a very nice signal, and we were able to rapidly translate that into a Phase 2 study,” Jonas explains. At 89 patients, it wasn’t as small as the brexanolone Phase 2, but according to Jonas, still fairly small when compared to a conventional Phase 2. “Moving SAGE-217 forward was done in almost record time, as we used our open-label methodology, almost like human probe studies, to inform Phase 2 design, which is very unconventional compared to how most biopharmas are doing studies these days,” he attests. Jonas views this approach as a return to basics; deploying the scientific method in the way it was meant to be deployed. “You make an observation,” he reiterates. “You then test it, which is the open label. That develops a methodology to further test the observation (i.e., Phase 2). Then you confirm the observation for Phase 3.”

Sage Therapeutics must know what it’s doing, for less than one month after reporting the positive Phase 3 results for brexanolone, the company was able to report positive top line results from its MDD study for SAGE-217. And again the market responded positively, as the stock leapt 70 percent higher from its previous day’s close of $91.90/share.

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This Beyond The Printed Page is a supplement to our July feature article on Jeff Jonas, M.D., CEO of Sage Therapeutics. We create this additional content when we don’t have enough room for all of an executive’s insights in the print edition. Subscribe to our monthly magazine here to get access to all of our interesting and helpful feature articles like the one on Jonas. We hope you enjoyed this latest Beyond The Printed Page installment.