- Shares in Sage Therapeutics, Inc. plunged by more than 20% Tuesday after the Cambridge biotech announced a Phase 3 study showed its lead candidate brexanolone was no better than placebo in treating patients with a severe type of epilepsy.
- Sage tested brexanolone in 132 patients with super-refractory status epilepticus (SRSE), a life-threatening condition resistant to multiple drugs commonly used to control patient seizures. The biotech had hoped to prove brexanolone could stabilize patients, allowing doctors to wean patients off of other treatment.
- The drug's striking failure will likely raise questions about future development in SRSE, as well as ratchet up the importance of an upcoming readout of another study testing brexanolone in postpartum depression.
Patients diagnosed with SRSE have already progressed through treatment with three prior therapies, initially with benzodiazepines and then followed with other anti-seizure drugs.
If patients continue to experience seizures after two lines of treatment, patients are typically admitted into the intensive care unit with refractory status epilepticus. Doctors then use anesthetics to induce a coma in hopes of restoring the brain's normal function while concurrently prescribing other antiepileptic drugs. After 24 hours, doctors usually attempt to wean patients off antiepileptic therapy.
The prognosis for patients who progress to this stage is particularly severe. Sage estimates roughly 40% of SRSE patients die, while another 35% recover but experience neurologic effects.
In Sage's study, though, brexanolone proved no better than placebo — 43.9% of patients receiving the drug were successfully weaned off treatment with other drugs without seizures returning for 24 hours, compared to 42.4% of patients who received placebo.
More than a third of patients treated open-label with brexanolone after the study's double-blind period did see a treatment response. But the lack of separation from placebo in the primary portion of the study will likely sap any remaining confidence in the drug's efficacy in SRSE.
Sage is studying brexanolone, also known as SAGE-547, in postpartum depression and data from a Phase 3 trial is expected to read out later this year. Results from an earlier mid-stage study boosted confidence in the drug's effect in that setting, although the sample size was particularly small.
Shares in Sage fell roughly 24% in initial trading Tuesday before regaining some of those losses to trade down near 15%.