Rare Daily Staff

PTC Therapeutics said updated interim data from the first part of its FIREFISH study investigating its experimental drug risdiplam in babies with type 1 spinal muscular atrophy showed “promising” improvements based on a standardized test of motor milestones in patients with neuromuscular disorders.

Spinal muscular atrophy is a genetic neuromuscular disorder that is the leading genetic cause of mortality in infants and toddlers caused by a missing or defective survival of motor neuron 1 (SMN1) gene, which results in reduced levels of SMN protein. The homologous SMN2 gene is predominantly spliced to a truncated mRNA, and only produces small amounts of functional SMN protein. Insufficient levels of SMN protein are responsible for the loss of motor neurons within the spinal cord leading to muscle atrophy and death in its most severe form.

The company’s experimental therapy risdiplam is a splicing modifier targeting the SMN2 RNA, restoring a functional transcript. Risdiplam is taken orally, crosses the blood brain barrier, and shows systemic distribution to the organs that are affected by low levels of SMN protein.

The data, presented at the at the 22nd Annual SMA Researcher Meeting, showed that at day 182, more than 90 percent of the babies achieved a greater than 4-point increase in CHOP-INTEND score compared to baseline. The Children’s Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP-INTEND) is a test designed to measure motor milestone development of patients with SMA Type 1.

In the study, the median increases in CHOP-INTEND scores were 14 points at Day 182 of treatment. In addition, risdiplam has been well tolerated at all dose levels and to date there have been no drug-related safety findings leading to withdrawal. No babies have required a tracheostomy or permanent ventilation since study initiation and no baby has lost the ability to swallow.

The company said that the CHOP-INTEND data were further supported by video footage presented at the meeting that showed babies in the study with the ability to control their head, roll, or sit. Part 2 of the pivotal study is ongoing. The SMA program is a collaboration between PTC, Roche, and the SMA Foundation.

“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, CEO of PTC Therapeutics. “The survival data and CHOP-INTEND scores are very promising, since babies with Type 1 SMA typically do not experience functional motor milestone improvement based on natural history.”

June 18, 2018
Photo: Stuart Peltz, CEO of PTC Therapeutics