Genentech/Roche and PTC Report New Positive Data for Risdiplam in SMA

Rare Daily Staff

Genentech, Roche, and PTC Therapeutics all reported positive results from part 2 of the pivotal FIREFISH study evaluating risdiplam in infants with type 1 spinal muscular atrophy.

The study met its primary endpoint of 29 percent of infants sitting without support for five seconds by month 12, something no type 1 SMA infants can do without therapy in the natural history of the disease.

The new data comes just weeks after the U.S. Food and Drug Administration extended the date for its review of Genentech’s New Drug Application for risdiplam to August 24, 2020 following the submission of additional data by the company. This included 12-month efficacy and safety data from the pivotal SUNFISH Part 2 study, the only placebo-controlled study ever undertaken in people aged 2-25 years with type 2 or type 3 SMA. At the time, the FDA said it needed to extend its decision so it could review all the data.

Spinal muscular atrophy (SMA) is a severe, inherited, progressive neuromuscular disease that causes devastating muscle atrophy and disease-related complications. It is the most common genetic cause of infant mortality and one of the most common rare diseases, affecting approximately one in 11,000 babies. SMA leads to the progressive loss of nerve cells in the spinal cord that control muscle movement. Depending on the type of SMA, an individual’s physical strength and their ability to walk, eat or breathe can be significantly diminished or lost.

Risdiplam is an experimental survival motor neuron-2 (SMN2) splicing modifier for SMA and is an orally-administered liquid. It is designed to durably increase and sustain SMN protein levels both throughout the central nervous system and in peripheral tissues of the body. It is being evaluated for its potential ability to help the SMN2 gene produce more functional SMN protein throughout the body. Roche’s subsidiary Genentech leads the clinical development of risdiplam, an experimental, orally administered survival motor neuron-2 (SMN2) splicing modifier for SMA, as part of a collaboration with the SMA Foundation and PTC Therapeutics.

Results from the FIREFISH study also demonstrated multiple secondary and exploratory endpoints, as type 1 SMA infants in the study achieved milestones not seen in natural history. Besides the ability to sit for 5 seconds able to sit without support, infants were able to maintain upright head control, roll to the side, and stand without support after 12 months of treatment. At 12 months, 95 percent of infants maintained the ability to swallow and 89 percent were able to feed orally. No new safety signals were identified in part 2 of the study.

At the time of analysis, the median duration of treatment was 15.2 months and the median age was 20.7 months. All but three infants out of 41 treated were alive and 35 were event-free. Without treatment, the median age of death or permanent ventilation was 13.5 months in a natural history cohort. Three infants experienced fatal complications of their disease within the first three months of treatment, and were not attributed by the investigator as related to risdiplam.

“These results confirm the clinically meaningful efficacy of risdiplam in infants with an advanced and difficult-to-treat disease,” said Levi Garraway, chief medical officer and head of Global Product Development at Genentech.

Risdiplam is an oral medication to be taken once daily. If approved, it will compete with Novartis’ Zolgensma, a once-and-done $2.1 million gene therapy approved one year ago, and Biogen’s Spinraza, which was approved in 2016 and is injected in the spine every four months. It lists for $750,000 in the first year of treatment and $375,000 annually thereafter.

Regulatory filings for approval of risdiplam have been submitted to health authorities in six other countries. The company said the risdiplam Marketing Authorization Application is also on track to be submitted to the European Medicines Agency in mid-2020.

Photo: Levi Garraway, chief medical officer and head of Global Product Development at Genentech