Roche abandons another Fragile X R&D program after PhII trials flunk out

A long, rough patch in Fragile X syndrome drug R&D just got longer and rougher. Roche ($RHHBY) has notified patient groups that both of its mid-stage studies for RG7090--an mGluR5 therapy--failed to hit the primary and secondary goals, prompting the pharma giant to shut down the program.

"Unfortunately, Fragxis (one of the clinical trials which enrolled 183 adults and adolescents) did not demonstrate the hoped for efficacy based on the primary and secondary endpoints employed," Roche neurosciences chief Luca Santarelli told the patient groups in a letter sent out on Tuesday. "As the FoXtail study (in children aged 5 to 13) was designed to evaluate the tolerability and safety of RG7090, conclusions about efficacy could not be reached. We will present data at upcoming medical meetings. We are disappointed that the results of Fragxis and FoXtail in their entirety do not provide the hoped for clinical improvement in the studied population, which has led us to discontinue the development of this compound in Fragile X. The program was not discontinued for safety reasons."

Fragile X is the most common genetic cause of autism. The condition triggers an intellectual disorder in both boys and girls, though it's more commonly affects males.

This isn't the first time that a once promising mGluR5 treatment foundered in the clinic. Seaside Therapeutics tried and failed with its own program, a setback that killed the company, which had been partnered with Roche. And Novartis ($NVS) has tried and failed with its own treatment, mavoglurant, which was scrapped last April after investigators failed to find any improvement over the placebo response. But patient groups say that despite the repeated clinical failures, the mGluR5 pathway remains one of the most promising approaches to coming up with an effective treatment.

"We don't believe that a short term trial in adults is going to be sufficient to prove or disprove the mGluR5 theory," Jeffrey Cohen, director of public policy and government affairs for the National Fragile X Foundation, said in an interview with FierceBiotech. "If anything the Seaside, Novartis, and Roche trials have convinced us that we need to look at much younger participants in the study to really have a chance of impact, when you have the ability to change a growing brain, to alter pathways that are being laid down much earlier in life." And Cohen added that it appears to be increasingly clear that the outcome measure Roche used (improvement in the Anxiety Depression and Mood Scale, or ADAMS, score) needs to be scrapped, substituting a cognitive measure.

Cohen says he hasn't learned yet whether Roche will try again on Fragile X. But he adds that several biotechs are in the clinic with their own programs, including Alcobra, an Israeli biotech, and Neuren Pharmaceuticals in Australia. Cambridge, MA-based Sage Therapeutics ($SAGE) has a $10 million NIH grant to work on Fragile X. According to, the small New Haven, Connecticut-based Marinus Pharmaceuticals ($MRNS) is also studying a potential treatment for the ailment.

A spokesman for Roche tells FierceBiotech that the pharma giant currently has no other programs in the clinic for Fragile X, but "we remain committed to developing medicines that will help people with neurodevelopmental disorders. Roche currently has two experimental compounds in Phase II clinical trials targeting neurodevelopmental disorders: RG7314, a V1a vasopressin receptor antagonist-V1a, being investigated in people with autism spectrum disorders and RG1662, a highly selective GABA-A a5 negative allosteric modulator, being investigated in people with Down syndrome."