Experimental Fragile X Treatment Arbaclofen Back in Development

Allos Pharma has obtained exclusive rights to arbaclofen, a potential treatment for fragile X syndrome.

The news comes more than seven years after Seaside Therapeutics decided to stop a clinical trial (NCT01013480) due to resource limitations, and at a time when the experimental treatment had reached Phase 3 studies (NCT01282268 and NCT01325220).

“Statistically significant and clinically meaningful efficacy was observed in a prior Phase 3 trial conducted by Seaside Therapeutics in humans with Fragile X Syndrome.” Randy Carpenter, MD, co-founder of Allos Pharma, said in a press release.  

Fragile X is caused by mutations in the FMR1 gene that lead to a deficit of FMRP protein. Studies have suggested that brain circuits driven by a signaling molecule known as GABA are impaired in people with fragile X, leading to excessive excitability of nerve cells. 

In 2018, the FRAXA Research Foundation awarded a $90,000 grant to the lab of Mark Bear, PhD, a professor at the Massachusetts Institute of Technology and co-founder of Allos Pharma, to identify new treatment targets for fragile X. Bear’s work included investigating arbaclofen, which selectively activates the GABA-B receptor that is involved in fragile X. The research also assessed the potential for people with fragile X to develop tolerance to potential treatments, which would limit their effectiveness over time in clinical trials.

“Animal research confirmed that arbaclofen can correct core pathophysiology [disease processes] in Fragile X that arises from dysregulation of neuronal protein synthesis and hyperexcitability,” Bear said.

The announcement that arbaclofen will be back in development came as welcome news to the fragile X community who participated in clinical trials conducted by Seaside several years ago. Although the trials ultimately failed to demonstrate benefits, families of participants reported marked improvements in core symptoms of the disorder.

“This news not only brings back hope for my son and the Fragile X community but reminds me that the amazing people who are dedicated to Fragile X will never give up on us,” Holly Usrey-Roos, whose son Parker was treated with arbaclofen, said in an interview with the FRAXA Research Foundation. 

“I never expected to get a phone call telling me that arbaclofen, the drug that changed my son’s life in the best ways, would be back,” she added “With it, we were able to do things just like everyone else: we could go to the public pool, we could go to the movies, and best of all, it led to my son talking.”

Allos Pharma now is working on the regulatory process to ultimately obtain approval for arbaclofen.