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Roche Presents New Data Supporting Safety and Efficacy of its Neuromuscular Therapies

September 24, 2021

Roche presented new data from its neuromuscular portfolio supporting the efficacy and safety of Evrysdi in babies with pre-symptomatic spinal muscular atrophy from birth to six weeks of age and data supporting the continued clinical investigation of gene therapy SFP-9001 in Duchenne muscular dystrophy.

Photo: Levi Garraway, chief medical officer and head of Global Product Development for Roche

The data was presented at the recently held World Muscle Society Virtual Congress (WMS 2021).

“These new data for Evrysdi may help extend the potential benefits of this medicine to the youngest SMA patients. Also, the data from SRP-9001 have helped to optimize the design of the upcoming phase 3 trial for DMD,” said Levi Garraway, chief medical officer and head of Global Product Development, Roche. “Our goal is to continue to lead the way in developing transformative medicines for neuromuscular diseases. We are grateful for the partnerships that are helping us to develop new therapies for people impacted by these devastating rare diseases.”

SMA is a severe, progressive neuromuscular disease that can be fatal. It affects approximately one in 10,000 babies and is the leading genetic cause of infant mortality. SMA is caused by a mutation of the survival motor neuron 1 (SMN1) gene, which leads to a deficiency of SMN protein, which is found throughout the body and is essential to the function of nerves that control muscles and movement. Without it, nerve cells cannot function correctly, leading to muscle weakness over time. 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.

Evrysdi is a survival of motor neuron 2 (SMN2) splicing modifier designed to treat SMA by increasing production of the survival of motor neuron (SMN) protein. It is administered daily at home in liquid form by mouth or by feeding tube. Evrysdi has been approved in more 50 countries including the United States and Europe and submitted in more than 30 countries.

At WMS 2021, data from the ongoing open label RAINBOWFISH study were presented. Four out of five of pre-symptomatic babies treated with Evrysdi for at least 12 months achieved standing and walking independently within the World Health Organization windows for healthy children. In addition, all five babies maintained the ability to swallow and were able to feed exclusively orally after 12 months of treatment.

Previously reported results showed that babies treated with Evrysdi for at least 12 months achieved Hammersmith Infant Neurological Examination (HINE-2) motor milestones, with 100 percent (n=5) able to maintain head control, sitting upright, rolling and crawling.

These data further add to the growing body of evidence supporting Evrysdi’s efficacy in a broad patient population. More than 4,000 patients have been treated with Evrysdi in clinical trials, compassionate use, and real-world settings.

DMD is a rare X-linked, progressive neuromuscular disease caused by mutations in the DMD gene that disrupts the production of functional dystrophin protein, leading to a loss of muscle function and premature death. DMD is one of the most common fatal genetic disorders, affecting approximately one in every 3,500 to 5,000 male births worldwide. Symptoms usually appear in infants and toddlers, with affected children presenting developmental delays such as difficulty walking, climbing stairs or standing from a sitting position. As DMD progresses, muscle weakness involves the arms, trunk, and other areas, meaning patients often require full-time use of a wheelchair in their early teens. Longevity is limited due to cardiac and/or respiratory failure.

SRP-9001 is an investigational gene therapy designed to deliver the micro-dystrophin-encoding gene directly to the skeletal and cardiac muscle for the targeted production of the micro-dystrophin protein to enable a durable clinical response. Sarepta Therapeutics is responsible for global development and manufacturing for SRP-9001 and plans to commercialize SRP-9001 in the United States upon receiving FDA approval. In December 2019, Roche partnered with Sarepta to accelerate access to SRP-9001 for patients outside the United States.

In DMD, three-year data from the open-label trial, Study SRP-9001-101, evaluating the safety of a single dose of the investigational gene therapy SRP-9001 in four ambulatory children aged 4 and 7 years old with DMD, were presented. The study showed that SRP-9001 was well-tolerated with key functional assessment, measured by the North Star Ambulatory Assessment (NSAA), demonstrating an overall improvement in motor ability compared to baseline. The improvements in motor abilities were maintained over three years, signifying a durable response. The results support the continuation of clinical investigation to further assess the benefit/risk of SRP-9001 in patients with DMD.

Roche, and partner Sarepta, also shared data from ENDEAVOR (Study SRP-9001-103), the first clinical trial using commercially representative SRP-9001 material for the treatment of DMD. Interim results from the first 11 participants in Cohort 1 (ambulatory boys aged 4-7 years) from the open label, ongoing Phase 1b study, provides evidence that SRP-9001 showed robust expression of micro-dystrophin and no new safety signals were identified.

In addition, results from Part 1 of Study SRP-9001-102, an ongoing, randomized, double-blind, placebo-controlled clinical trial evaluating the safety, efficacy, and tolerability of a single dose of SRP-9001 in 41 boys with DMD, showed that the study met its primary biological endpoint of change in micro-dystrophin protein expression from baseline. Participants treated with SRP-9001, generally showed an increase in NSAA total score compared to placebo at 48 weeks, although this increase did not achieve statistical significance compared to that of patients who received placebo. The safety profile was consistent with prior studies, with no new safety signals identified.

The results of these studies provide important information for SRP-9001’s ongoing clinical development program, with outcomes from Study 101 and 102 informing the design of the phase 3 trial for SRP-9001, due to commence globally by the end of the year.

Author: Rare Daily Staff

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