Roche's Oral SMA Therapy Evrysdi Shows Sustained Improvement in 80% of Patients in Long-Term FIREFISH Trial

Today, Genentech, a member of the Roche Group, announced positive two-year results from the FIREFISH study evaluating its innovative spinal muscular atrophy (SMA) therapy, Evrysdi (risdiplam), in infants aged 2 to 7 months with symptomatic Type 1 SMA. Among infants treated with the therapeutic dose of Evrysdi, 80.9% (17/21) showed sustained improvement in symptoms and achieved motor milestones. Evrysdi received FDA approval in August, becoming the first oral therapy approved for the treatment of patients with SMA.

Spinal Muscular Atrophy (SMA) is a severe, progressive, and potentially fatal neuromuscular disorder. It affects approximately 1 in 10,000 infants and is the leading genetic cause of infant mortality. SMA results from mutations in the SMN1 gene, leading to a deficiency of the survival motor neuron (SMN) protein. This protein is present throughout the body and is essential for the function of muscles and motor neurons. Although SMA primarily manifests during infancy or early childhood, patients can be of any age, ranging from infants to adults.

Evrysdi is a small-molecule mRNA splicing modifier targeting the SMN2 gene, jointly developed by Genentech and PTC Therapeutics. Although the SMN2 gene carried in the human body can also express SMN protein, erroneous mRNA splicing results in very low levels of normal SMN protein expression, which is insufficient to compensate for the SMN protein deficiency caused by SMN1 gene mutations. Evrysdi modulates the splicing of SMN2 gene mRNA, thereby increasing the levels of mRNA capable of expressing functional SMN protein and alleviating symptoms in patients with spinal muscular atrophy (SMA). Evrysdi is formulated as an oral liquid that can be administered at home either orally or via a feeding tube.

Exploratory analysis indicated that two years after treatment, 88% of infants were alive and did not require permanent ventilation. Furthermore, 59% (10/17) of the infants were able to sit unsupported for at least 5 seconds, representing an increase compared to one year post-treatment (7/17).

After two years of treatment with Evrysdi, 71% of infants achieved a CHOP-INTEND motor function score of 40 or higher, and all infants had higher scores at 24 months than at 12 months. Among the 14 infants who survived to age 2 years, 100% retained swallowing ability.

“We are highly encouraged by the results from the second year of treatment with Evrysdi,” said Dr. Levi Garraway, Chief Medical Officer and Head of Global Product Development at Roche. “These findings continue to add to the evidence demonstrating the efficacy and safety of Evrysdi in pivotal clinical trials, and we look forward to further evaluating the impact of this innovative therapy on patient survival and motor function during long-term follow-up.”

References:

[1] Genentech Presents New 2-Year Data for Evrysdi (risdiplam) in Infants With Type 1 Spinal Muscular Atrophy (SMA). Retrieved September 28, 2020, from https://www.businesswire.com/news/home/20200927005081/en

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