An experimental drug designed to improve brain function in people with nerve-degrading disorders has failed a mid-stage study that tested it against Parkinson’s disease.
The trial enrolled almost 90 participants, who once a day were given either a placebo or a drug from Sage Therapeutics called SAGE-718. Summary results released Wednesday showed no significant difference between the two groups in how their mental abilities changed over the course of six weeks, as measured by a scale clinicians use evaluate cognition.
Sage said its drug was generally well tolerated, though nearly half of the participants who took it had at least one “treatment emergent adverse event.” Researchers reported 21 volunteers had such events in the study’s drug arm, and while the majority were mild to moderate, two were deemed “severe.” Three serious adverse events were also observed.
Among those given placebos, 27 — or 63% of the group — experienced at least one treatment emergent adverse event.
According to Sage, the trial’s results didn’t hint SAGE-718 had any meaningful benefit on other, “exploratory endpoints,” including a different scale specifically calibrated to assess cognition in Parkinson’s patients. As such, the company doesn’t plan to further advance the drug for this indication.
Sage is still testing SAGE-718 across three additional trials that should have data this year. One, codenamed “Lightwave,” is focused on people with mild cognitive impairment and mild dementia due to Alzheimer’s disease. The other two, “Surveyor” and “Dimension,” are investigating whether the drug can help Huntington’s disease patients with cognitive impairment.
In a statement, Sage’s CEO Barry Greene noted that, while the newly disclosed results are disappointing, they “do not necessarily predict” how SAGE-718 will perform in other nerve-eroding conditions.
“Although cognitive impairment is common in neurodegenerative disorders, the underlying pathophysiology and symptomatology in Parkinson’s disease is distinctive,” Greene said.
Analysts at the investment bank Raymond James aren’t sold on that argument, however. In a note to clients, analyst Danielle Brill wrote that her team didn’t find the Parkinson’s results “all that surprising,” especially given some elements of the trial’s design. Brill highlighted how Sage evaluated a lower dose than it did in previous testing and used performance measures “susceptible” to issues like placebo effects.
“In terms of readthrough to the rest of the ‘718 trials, we maintain our skepticism and believe the probability of success is very low,” Brill wrote.
Analysts at Stifel and RBC Capital Markets noted how SAGE-718 has always been a “high-risk, high-reward” program, meanwhile.
As with most diseases of the brain, Parkinson’s drug development has proven difficult. Therapies that replace the neurotransmitter dopamine are effective, but their benefit wanes over time.
Just last year, a nearly 100-person trial found a drug from a small biotechnology company called Aptinyx was no better than a placebo at improving everyday function and cognition in patients with the disease. A few months later, Biogen scrapped a late-stage study of a Parkinson’s drug it’s been developing with biotech partner Denali, though the companies said the decision was tied to trial logistics and not to any concerns about the drug’s safety or effectiveness.
Shares of Sage sunk 22% Wednesday morning, to trade near $12 apiece. The company’s stock price is currently down more than 70% from a year ago, in large part because of a decision from the Food and Drug Administration that severely cut the commercial prospects for one of Sage’s most closely watched medicines.
