Rare Daily Staff

Roche subsidiary Genentech reported positive topline results from the pivotal second part of the FIREFISH study evaluating risdiplam in infants aged 1 to 7 months with type 1 spinal muscular atrophy, the most severe and most common subtype of the debilitating disease.

Spinal muscular dystrophy (SMA) is a rare genetic disease caused by a mutation in the SMN1 gene, which encodes the protein critical for the maintenance and function of specialized nerve cells called motor neurons. If there is not enough functional SMN protein, then the motor neurons die, leading to debilitating and often fatal muscle weakness. SMN protein is found throughout the body and increasing evidence suggests SMA is a multi-system disorder and the loss of SMN protein may affect many tissues and cells, which can stop the body from functioning.

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. 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.

Risdiplam is an experimental survival motor neuron-2 (SMN-2) splicing modifier for SMA and is an orally administered liquid. It is designed to increase and sustain SMN protein levels both throughout the central nervous system and peripheral tissues of the body. It is being evaluated for its potential ability to help the SMN-2 gene produce more functional SMN protein throughout the body.

Risdiplam met the primary outcome measure of the second part of the two-part FIREFISH study in 41 infants aged 1 to 7 months with type 1 SMA, which assessed the proportion of infants who could sit without support for 5 seconds after 12 months of treatment. Safety for risdiplam was consistent with its known safety profile and no new safety signals were identified. To date, more than 400 patients have been treated with risdiplam across four studies with patients ranging from birth to 60 years old, with no treatment-related safety findings leading to study withdrawal in any risdiplam trial.

“This large, global trial confirms the efficacy of risdiplam in an advanced and difficult-to-treat population, including many infants whose disease had already progressed significantly before starting treatment,” said Levi Garraway, chief medical officer and head of global product development. “We are very encouraged by these results and we look forward to sharing them with regulators.”

Added to positive data reported in November from the SUNFISH study evaluating risdiplam in people aged 2 to 25 years with type 2 or type 3 SMA that showed improved motor function after one year of treatment compared to placebo, the new data bolsters the likelihood Roche and partner PTC Therapeutics will win U.S. Food and Drug Administration approval for the drug by their upcoming PDUFA date in late May. It will also add another compound to the SMA therapy arsenal to rival already approved therapies for SMA: Novartis’ gene therapy Zolgensma and Biogen’s antisense oligonucleotide Spinraza, which is injected into the spine every four months.

Zolgensma, which carries a price tag of $2.1 million, is only approved for patients less than 2 years old. Roche has already said it will make risdiplam cheaper than Spinraza, which costs $750,000 for the first year, and $375,000 per year thereafter.

Photo: Levi Garraway, chief medical officer and head of global product development

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