Sage Therapeutics’s closely watched epilepsy drug, brexanolone, did not do much better than a placebo in helping patients with a severe type of the condition, data from a phase 3 clinical trial show.
The Cambridge biotech expected brexanolone to lead to its first-ever drug approval. Instead, its shares dropped almost 14 percent, to $76.40 in trading Tuesday.
The drug was intended to treat a grave form of uncontrollable epilepsy called super-refractory status epilepticus, or SRSE. A continuous infusion of brexanolone over six days weaned 44 percent of these patients from medically induced comas without seizures returning for 24 hours. The comparable response rate for SRSE patients given a placebo was 42 percent. The small difference favoring brexanolone was not statistically significant, failing the primary endpoint of the 140-patient study, Sage said Tuesday.
“This is not what we hoped the study would be,’’ said Sage chief executive Jeff Jonas.
Sage continues to study brexanolone in other neuropsychiatric diseases, including a phase 3 clinical trial of women with severe postpartum depression. Results from that trial are expected later this year.
SRSE is a complicated and relatively understudied condition because the nonstop seizures can be triggered for different reasons — underlying epilepsy, of course, but also traumatic brain injury, drug overdose, stroke, and some autoimmune diseases.
A successful outcome from the phase 3 clinical trial was never a sure thing, but the placebo-like response rate shown by brexanolone will raise new concerns about the drug’s future.
The brexanolone response rate in earlier SRSE studies was 73 percent but there were no control arms for comparison and just 29 patients were treated. The earlier studies also used a slightly different definition of response from what was used in the phase 3 trial. Looking back, the robust efficacy signal seen in the previous studies was not to be trusted.
Patients’ experience with brexanolone for SRSE varied considerably. One of those who appeared to respond was David Logan, a 56-year-old resident of Dorchester.
He had such a strong recovery after being given the drug that he had hoped it could help many other patients with the frightening condition.
Logan’s first seizure came on suddenly during a Memorial Day weekend barbecue that he and his wife, Mary, were hosting for friends and family. Hearing a strange banging sound on the upper floor of their house, Mary investigated and found Logan convulsing and unresponsive.
“He was on the floor, drooling from both sides of his mouth,’’ recalled Mary Logan, holding back tears while recalling what she describes as the hardest months of her life. “I didn’t know what was wrong. I have known David since I was 15 but I had never seen this with him before.’’
He was taken to the emergency room at Boston Medical Center. He spent a few days in the hospital while doctors tried to determine the cause, without success. Eventually, feeling better, he was sent home with epilepsy medicine. Two days later, Mary Logan found him seizing again. This time, the seizures would not stop. He was admitted to Boston Medical Center’s Neurocritical Care Unit, under the care of a team led by Dr. Anna Cervantes and Dr. Courtney Takahashi.
Over the next two weeks, Cervantes said, Logan was treated with five epilepsy medications but none halted the seizures. He was placed in a medically induced coma. Three attempts were made to wean him in the hope that the deep anesthesia would reset his brain’s activity to normal. Each time doctors tried to wake Logan, monitoring equipment showed his brain still seizing. He was diagnosed with SRSE.
Boston Medical Center was not set up as an investigatory site for Sage’s brexanolone phase 3 clinical trial, but Cervantes, who had recently attended a lecture where the drug and the study were discussed, believed Logan was a strong candidate. Cervantes contacted Sage, which agreed to provide brexanolone.
The drug was administered over six days. This time, when doctors woke him from his coma, his brain activity looked normal. After another six weeks of hospitalization and rehabilitation, Logan walked out of Boston Medical Center. He remains free of seizures.
But Logan’s success story was not replicated enough across the phase 3 clinical trial to demonstrate that brexanolone was the reason for his recovery.
“Though we saw a dramatic effect with the use of brexanolone for David, the results of the randomized trial did not support a benefit to use in all SRSE patients,’’ said Cervantes. “We know that SRSE is a heterogenous disease — meaning people can have epilepsy from a myriad of causes — some structural, some infectious, some metabolic. Perhaps brexanolone may be beneficial in a subset? Despite the trial findings, I am hopeful that future research will find a way to treat this rare and devastating disease.’’
Adam Feuerstein can be reached at adam.feuerstein@statnews.com. Follow him on Twitter @adamfeuerstein.
