FDA Shifts Risdiplam Decision to August to Include Data on Older Patients

The U.S. Food and Drug Administration (FDA) has extended its review of risdiplam as an oral treatment for spinal muscular atrophy (SMA) by three months, pushing the decision due date to August 24 from May 24.

This extension was based on additional clinical data submitted by Roche — one of risdiplam’s developers — three months after the investigational therapy received priority review status, and in close collaboration with the FDA.

Due to the volume of data submitted, the agency said it needed more time to finish its review.

Roche’s submission included one-year data from the second part of the Phase 2/3 SUNFISH study (NCT02908685) — the first placebo-controlled trial to include children and young adults (ages 2 to 25) with SMA types 2 and 3. These results are expected to help provide access to risdiplam for a broad range of SMA patients, should it be approved.

The FDA also stated that no review issues of concern have been identified to date.

“We are encouraged that the FDA has no substantive review issues. Their interest in the additional results from the clinical studies demonstrating risdiplam’s activity supports our goal of enabling access to this important therapy for all SMA patients,” Stuart W. Peltz, PhD, CEO of PTC Therapeutics, one of risdiplam’s developers, said in a company press release.

“We are working closely with the FDA to support the review of risdiplam. Our goal is to bring this therapy to infants, children and adults living with SMA as quickly as possible,” Levi Garraway, MD, PhD, Roche’s chief medical officer and head of global product development, said in a separate release by Roche.

Risdiplam — developed by Roche and Genentech (a member of the Roche group) in collaboration with PTC Therapeutics and the SMA Foundation — is an oral liquid therapy designed to increase the production of a functional survival motor neuron (SMN) protein, which is impaired in SMA patients. SMN is essential for muscle health.

If approved, risdiplam will be the first oral and “at home” disease-modifying SMA therapy, and the second to work by boosting the ability of the SMN2 gene to produce a functional SMN protein. Spinraza, developed and marketed by Biogen, is the first; it was approved in December 2016.

Risdiplam’s approval request is supported by data from the second part of the ongoing Phase 2/3 FIREFISH (NCT02913482) and SUNFISH trials, which include more than 200 patients with type 1, 2, and 3 SMA between 1 month and 25 years old.

This patient population more closely represents the real-world spectrum of people living with SMA, and includes many patients previously underrepresented in clinical trials.

Both trials met their primary effectiveness goal, with risdiplam treatment resulting in significant improvements in motor milestones in infants with SMA type 1 and in motor function in children and young adults with type 2 and 3 disease.

The treatment has been well-tolerated, with no patient yet stopping its use.

The recently submitted SUNFISH data concerns detailed results of the 180 wheelchair-bound type 2 and 3 SMA participants who were given risdiplam or a placebo for one year.

Data released to date report that a larger proportion of patients treated with risdiplam showed significant motor function improvements, particularly those in the youngest age group (2–5 years old),  or stabilization — particularly in the oldest age group (18–25 years old) — compared with those on a placebo.

In older SMA patients, treatment goal is to stabilize motor function to prevent further disability, so these findings are considered relevant for this patient population.

“We strongly believe in the potential of risdiplam as a new therapeutic option and recognize that unmet need remains in the treatment of SMA,” Garraway said.

“Enabling access to a home-administered oral therapy for a broad patient population is critically important and we look forward to the FDA living up to its commitment to review the application as quickly as possible,” Peltz added.

Roche has submitted similar marketing applications of risdiplam to regulatory agencies in Indonesia, Taiwan, Chile, Brazil, South Korea, and Russia. A submission is also imminent in China, and filing to the European Medicines Agency and other international markets remains on track for mid-year.