Roche bags breakthrough status for autism hope balovaptan

Roche has been awarded breakthrough status for a drug that has shown some signs of activity in autism spectrum disorders, according to reports.

Balovaptan (RG7314) aims to treat autism by modulating the activity of vasopressin, a hormone that first emerged as a possible drug target in the disorder a few years ago. It blocks the activity of the V1a vasopressin receptor subtype and is currently in phase 2 testing.

Reuters said this morning that the FDA granted breakthrough status to the program in the hope of accelerating its progress through development and onto the market.

Vasopressin is a neuropeptide that helps neurons in the brain communicate with each other and seems to play a role in social bonding. In the case of autism, higher levels in the blood correlate with better social functioning in individuals.

The neuropeptide is being tested itself as a nasal spray by scientists at Stanford University to see if it can enhance social functioning in people with autism. A preliminary study in 50 patients showed evidence of improvements last year, and the Stanford team is now progressing with a 100-patient trial due to complete around the end of 2022.

A similar approach has been tried with oxytocin, another neuropeptide that was shown to enhance social functioning in a small study in children with autism reported last year—also conducted at Stanford—but has also failed other clinical trials. As with vasopressin, higher levels of oxytocin seem to be linked to higher functioning, so the team are selecting children with lower levels of the neuropeptide in additional studies.

Roche’s approach is rather different, speculating that blocking the activity of the hormone at one receptor will help improve social functioning and avoid potential side effects of increasing vasopressin across the board, which some scientists believe could lead to increased aggression.

In a study in adult males with autism, balovaptan showed a trend towards activity on social functioning scores but failed to reach statistical significance but was able to achieve a significant improvement on an adaptive behavior rating scale at higher doses.

The pharma industry has had a tough time trying to develop an effective treatment for autism, with a string of product failures in recent years, with Novartis, Roche and Seaside Therapeutics among those with defunct programs.

A number of companies have also tried to develop vasopressin receptor blockers for other neurological conditions, with mixed results. Azevan Pharma has two V1a antagonists—SRX246 and SRX251—in trials for people with intermittent explosive disorder (rage outbursts), post-traumatic stress disorder (PTSD) and irritability associated with Huntington’s disease, but as yet has no program in autism.

Meanwhile, AbbVie and Sanofi have both developed V1b antagonist for depression and anxiety which failed to make it beyond midstage trials, although Taisho Pharma still has a V1b blocker in phase 2 as an adjunctive treatment for major depressive disorder.