Disappointments aside, optimism for Fragile X drugs

Four years ago when drug trials started, families dealing with the genetic disease Fragile X were filled with optimism.

For the first time, they had hope that their loved ones might get a break from the anxiety, agitation, communication and cognitive problems of Fragile X. Perhaps they'd even be able to learn.

Upbeat stories trickled out. Teenagers were able to hold their first real conversation. Boys stopped hitting themselves and knocking their heads against walls. Families were able to eat out at restaurants, celebrate birthdays, do some of the "normal" things that define other people's lives but never theirs.

"You could taste it," Katie Clapp said about the community's optimism.

Then the good news stopped.

The drugs failed in multiple trials. Novartis, a leader in the field, said a few weeks ago that it would end its research into the drug mavoglurant. Seaside Therapeutics, a Massachusetts start-up working on a different drug, arbaclofen, has essentially shut down.

This is a familiar story in drug development: enthusiasm and hope, followed by years of effort and then failure. Barely one in 10 drug candidates makes it through development. Then the search for promising science, money and community support has to begin all over again.

"We are not giving up, said Clapp, mother of 24-year-old Andrew Tranfaglia, who was diagnosed at age 2 with Fragile X.

These drug trials were unusual because they were the first to address the underlying symptoms of both Fragile X and autism, a condition now believed to affect one in 68 school-age children with social and communication problems and repetitive behaviors.

And the drug trials seemed to work for some, including Tranfaglia, who was taking mavoglurant, which tamps down some overexcited signals in the brain. When he started the drug, he began to smile more, his mother said.

"A calm but complete smile that went from his mouth to his eyes," Clapp said. "It's amazing that a medicine could do that."

But to declare a medication trial a success, drug developers have to predict what the drug will do and then show that it performs as promised. The improvements Tranfaglia experienced weren't predicted, so they couldn't be measured or credited to the medication.

Arbaclofen showed even more promising results in a subset of patients — but not overall, said Robert Ring, chief science officer for the advocacy group Autism Speaks, which helped fund the research. "Many of us who saw the data really do believe there was a response that's worth following up," he said. Now, the challenge will be finding someone to pay for another clinical trial that will cost millions, if not tens of millions.

Roche, which had partnered with Seaside on arbaclofen, has a third drug in trials called RG709, which is similar to Novartis' mavoglurant. Its trial in children accepted its final patients last month. Results routinely take a year or more to analyze before being made public.

Clapp, who runs a research and advocacy group for Fragile X called Fraxa, said there are two other possible drug candidates she'd like to get into clinical trials: lithium and minocycline. Both are old drugs that are not protected by patents, so no drug companies will fund the research, though. Clapp, of West Newbury, Mass., will have to fundraise herself to pay for the studies.

In the meantime, Clapp said she's counted the number of mavoglurant pills her son has left — enough to get him through August.

"Obviously, I'm very scared about that," she said. "It's going to be a last, sweet summer."