PTC Therapeutics Presented Updated Interim Data from SMA Clinical Trial

Neuromuscular Disorder

PTC Therapeutics presented updated interim clinical data from Part 1 of its FIREFISH clinical trial of risdiplam (RG7916) in babies with Type 1 Spinal Muscular Atrophy (SMA) at the 22nd Annual SMA Researcher Meeting.

SMA is a severe, genetic neuromuscular disease that can be fatal. It shows up in 1 in 6,000 to 10,000 live births annually. There are four types named for age of initial onset of muscle weakness and symptoms. Type 1 (infantile), Type 2 (intermediate), Type 3 (juvenile) and type 4 (adult).

Risdiplam is an investigational splicing modifier targeting the survival motor neuron 2 (SMN2) RNA. It restored a functional transcript, and is taken orally. The drug can cross the blood-brain barrier and has systemic distribution to the organs affected by low levels of SMN protein.

The data was presented by Giovanni Baranello of the Fondazione Istituto Neurologico Carlo Besta in Milan, Italy. It showed at Day 182 over 90 percent of the babies in the trial had a greater than a four-point increase in CHOP-INTEND score compared to baseline. The CHOP-INTEND data was supported by video footage shown by Baranello of babies showing antigravity movements, the ability to control their head, roll, or sit.

The SMA program is a collaboration between PTC, Roche, and the SMA Foundation. The SMA program was launched by PTC with the SMA Foundation in 2006. In November 2011, Roche obtained an exclusive worldwide license to the PTC/SMA Foundation SMN2 alternative splicing program. Risdiplam’s development is being executed globally by Roche, including its Genentech team. The SMA program is overseen by a Joint Steering Committee with members from all three organizations.

“We are delighted that up to 6.5-fold increase of protein production has translated into clinical impact for these babies in the FIREFISH study,” said Stuart Peltz, PTC Therapeutics’ chief executive officer, in a statement. “The survival data and HCOP-INTEND scores are very promising, since babies with Type 1 SMA typically do not experience functional motor milestone improvement based on natural history. We look forward to sharing updates for the programs as the data further develop at upcoming medical meetings.”

Currently, the only therapy approved for SMA is Biogen’s Spinraza, which is delivered by an injection to the spine. Should the PTC drug become available orally, if it were as effective as Spinraza, it would be a notable competitor. It won’t be the only one, however. Novartis recently acquired AveXis in April for $8.7 billion, and it has a gene therapy for SMA Type 1, AVXS-101, in its pipeline. It is a gene therapy that works to replace the defective SMN1 gene.

Cytokinetics also released data from its Phase II clinical trial of reldesemtiv in patients with SMA, which showed promise as well. In that clinical trial, 70 patients with Type II or Type III who were 12 years of age or older were randomized two-to-one, stratified by ambulatory ability, to receive reldesemtiv or placebo twice a day for eight weeks. The first cohort received 150 mg of the drug or placebo and the second received 450 mg. Multiple evaluations of skeletal muscle function and fatigability were performed. The 450 mg dose showed statistically significant results in the Six Minute Walk test, although it dropped below a significant response at eight weeks.

Of the PTC trial, Baranello stated, “I am impressed by the clinical data and the changes reported by the patients’ families. Data on motor function seem more encouraging when we consider that we are seeing motor function improvements and milestones achievement at this early stage of the study, which was essentially a dose-finding study and most of the infants included have received their first dose after the age of five months. It is exciting to see evidence of clinical benefit from a systemic oral treatment for SMA.”

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