- Acadia Pharmaceuticals on Monday said an experimental drug it's developing for a rare neurological condition met both goals of a late-stage clinical trial, potentially positioning the San Diego-based biotech company to ask the Food and Drug Administration for approval.
- Acadia's drug, called trofinetide, outperformed placebo on two assessments used to measure symptoms and progression associated with Rett syndrome, an inherited disorder that typically affects girls and impairs function and development. After 12 weeks of treatment, the difference versus placebo was statistically significant, the company said.
- But trofinetide was frequently linked to side effects, particularly diarrhea and vomiting, that led to nearly a fifth of study participants who received it to discontinue treatment. Most reactions were mild or moderate, according to Acadia, and the company has developed a plan to help manage gastrointestinal problems, which are also a common symptom of Rett.
No treatments are available for Rett syndrome, although a number of companies, including Acadia, aim to change that.
Acadia's drug is a synthetic version of a protein found on a hormone linked to normal brain development, designed to reduce inflammation and promote the function of circuitry between neurons.
In the company's Phase 3 trial, which included 187 girls and young women with Rett, treatment appeared to improve symptoms affecting mood, breathing, hand movement and other functions. Measured on a caregiver assessment called the Rett Syndrome Behavior Questionnaire, participants who received trofinetide scored on average five points lower after 12 weeks of treatment than they did at the study's start. Those given placebo, by comparison, scored an average of two points lower.
According to Acadia, one or two points can matter, as each behavioral item on the questionnaire is rated as 0 (not true), 1 (sometimes true), or 2 (often true).
On a separate rating scale assessed by physicians, the difference between trofinetide and placebo was more slight — 0.3 points after 12 weeks — although still statistically significant.
"We think that these data, though not overwhelming on efficacy, will likely meet the bar for approval in a rare disease where there are no approved treatments available," Paul Matteis, an analyst at Stifel, wrote in a Dec. 6 note to clients.
Nearly 93% of the 93 study participants who received trofinetide experienced a side effect, compared to 54% given placebo, although only three events in each group were classified as severe.
Eighty percent of study volunteers on Acadia's drug experienced diarrhea and 27% reported vomiting, versus 19% and 10%, respectively, on placebo. All told, 17% of people in the trofinetide group discontinued treatment due to side effects, compared to 2% on placebo.
On a conference call Monday, analysts questioned whether the high rate of gastrointestinal side effects might have effectively "unblinded" the study, meaning participants (and their doctors) could have known they were receiving the drug, potentially skewing the results. But Acadia said it was confident that didn't happen, pointing to sensitivity analyses it performed to test the possibility of unblinding.
Still, Chris Howerton, an analyst at Jefferies, wrote in a note to clients that questions around the drug's benefit and side effects could spur the FDA to call in outside experts for help reviewing the data, should Acadia file for approval.
The company says it plans to do that around the middle of next year, following a meeting with the FDA it aims to schedule in the first quarter.
But Acadia and the FDA haven't seemed on the same page recently. In March, the agency informed the company of "deficiencies" in its application for approval of another drug, pimavanserin, for dementia-related psychosis. When the FDA subsequently rejected the treatment, Acadia said it was surprised by the feedback and claimed the regulator had backtracked from previous agreements about the study.
Investors appeared to welcome news of the study success in Rett syndrome, sending shares, which had fallen by nearly half in March, higher by 8%.