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Sage Points to Tremor Data to Back Up “De-Risked” Neuro Drug Plan

Xconomy Boston — 

Companies are always looking to increase their odds of success, and Sage Therapeutics believes it’s come up with a clinical strategy to take some risk out of a risky business.

Sage (NASDAQ: SAGE) today is reporting the results of a small, exploratory study of its lead drug, SAGE-547, in patients with essential tremor, a neurological disorder characterized by debilitating, rhythmic trembling of the hands, head, voice or legs.

Essential tremor affects more than 10 million Americans and many more around the world, and Sage says that current treatments—among them primidone and propranolol—are only moderately effective.

Sage says the study results are positive. The drug appeared to reduce the frequency and severity of tremors, compared to a placebo, in the 25-patient trial. But more broadly speaking, the company points to these results as reinforcement for its development strategy: Sage-547, an intravenous drug, isn’t the one the company eventually wants to bring forward as a treatment for essential tremor. Rather, it’s a stand in for an oral, chronic therapy the company hopes to advance based on signals it’s seen from this small trial.

In other words, CEO Jeff Jonas (pictured above) says, Sage is using SAGE-547 as a “probe” for a library of molecules that can be specifically tailored based on how the original drug performed.

SAGE-547 is showing promise for a life-threatening form of seizure called super refractory status epilepticus and has reached Phase 3. It wants to see if the same type of drug—a therapy that acts on the inhibitory transmitter called GABA—would work for other diseases. So rather than going the traditional and time consuming route of discovering, developing, and running animal studies for drugs that also act on GABA, Sage is using SAGE-547 in small exploratory studies of patients with different diseases where that approach might also make sense. If it sees enough of a signal in these small studies, it’ll take a different, perhaps better drug from its library forward.

By doing this, Sage believes it’ll have a better chance of succeeding in those later trials. In this case, for instance, Sage says the tremor data increase its confidence that a follow-up GABA-modulating drug from its library—perhaps one called SAGE-217 that’s close to Phase 1 testing, perhaps another—could succeed. Sage has also run a trial like this with SAGE-547 in postpartum depression, and has said the findings—even though they were from four total patients—justified moving the program forward to a placebo-controlled trial.

Jonas argues that this strategy is unique, and says that these exploratory trials only need to answer one question: are the results good enough to keep going with a similar drug?

“I would say the study tells yes,” he says.

Unique or not—a few veteran drug developers I polled yesterday termed this type of approach “pretty standard practice”—the strategy holds plenty of risk. Jonas counters that even with a tiny study population, where one or two patients can sway the data, the way patients have responded to higher doses in stepwise fashion is a significant point in the study’s favor. He also contends given the work Sage has done internally, there’s “no scientific reason to believe” that Sage’s follow-on drug, whether it’s SAGE-217 or something else, won’t react the way the company expects.

It’ll nominate a compound next year—one that, unlike SAGE-547, is a pill that could be taken every day, rather than infused at a hospital.

“We won’t know until we put [the drug] into humans that we’re not wrong,” he says. “But I think all this [approach] does is increase the likelihood that we’re right. And that’s all drug development is. Every day you just try to get closer to an answer.”