Seaside Therapeutics Inc. reluctantly terminated an open-label extension study of STX209 (arbaclofen), for Fragile X syndrome, due to resource limitations. The company said the decision was not related to any safety issues with the drug, and expressed regret that the termination of the trial would be "disruptive and disappointing for many families."

STX209 did not meet its primary endpoint of reducing social withdrawal in the recently completed Phase III trial, but the Cambridge, Mass.-based company is planning to complete another Phase III, placebo-controlled study in children with Fragile X. If those results are positive, Seaside will press forward toward next steps for registration of the drug.

According to Jeffrey Cohen, director of government affairs for the Fragile X Foundation, the trial termination will disappoint a great many patients who were seeing benefits from the drug. About 300 patients were participating, and had been for as long as three years. "We were seeing some significant results," Cohen said. Those included "language where there was none," social engagement and reduction of tactile defensiveness. "Some of these families literally had never gotten a hug from their kids," Cohen said, and some of those children became able to tolerate an embrace from a parent for the first time.

Those families now face the prospect of losing the dramatic improvements they have seen and attributed to STX209. "It scares the hell out of them that they're going to go off the drug, and their kids are going to revert," Cohen said.

Seaside began its randomized, double-blind, placebo-controlled Phase III study of STX209 in June 2011, with the goal of evaluating the drug's effect on social impairment in adolescents and adults, ages 12 to 25, with Fragile X syndrome. The company began a second study in children ages 5 to 11 shortly after.

STX209 is an oral selective gamma-amino butyric acid type B (GABA-B) receptor agonist that Seaside contended may play a role in improving core symptoms of Fragile X.

In a Phase II study, the drug produced clinically meaningful improvements in social impairment.

Although the drug missed its primary endpoint, Cohen said that's not the whole story, and that many benefits seen by families in the trial have not been taken into consideration.

"From our perspective, this failed trial that was just announced a couple days ago is more as a result of the narrow review process than it is the promise of the drug," Cohen said.

The Fragile X Foundation published an open letter in response to the trial termination. In it, the foundation wrote, "While this may be a difficult time for many, it is important for us to remember there has never been more of a reason to remain optimistic. There are many new medication targets under investigation and researchers are continuing their ground-breaking work toward translating these potential treatments to individuals with fragile X syndrome in the future. In addition, at this time, we are still aware that Seaside plans to pursue FDA approval pending the results of the placebo-controlled studies."

This isn't the first time STX209's benefits have proved difficult to pin down. Last September, STX209 missed its primary endpoint of improvement in irritability in patients with Fragile X syndrome in a Phase II trial, although a post hoc analysis showed the drug led to decreased social withdrawal. (See BioWorld Today, Sept. 21, 2012.)

That result gave the company and patients hope that the drug would prove its worth in the ongoing Phase III trial, which had social withdrawal as its endpoint.

In a letter posted on the company's website, Seaside said, "We are disappointed that the primary endpoint was not met in trial 209FX301 and, at this point, STX209 must be regarded as an experimental drug of unproven safety and efficacy."

STX209, arbaclofen, is a derivitive of baclofen, a drug that has been on the market for a number of years and is used primarily for treatment of spastic movement disorders like cerebral palsy. Patients dismissed from the trial may have the option to continue treatment with baclofen. "At least some patients will be trying that," Cohen said.

Seaside Therapeutics was not available to comment on the discontinuation of the trial.