PTC Therapeutics (PTCT) Positive Data from FIREFISH Study of Evrysdi in Infants with Type 1 SMA Published in NEJM
PTC Therapeutics, Inc. (NASDAQ: PTCT), today announced the publication of results from the dose finding Part 1 of the pivotal FIREFISH study evaluating Evrysdi™ (risdiplam) in infants with symptomatic type 1 spinal muscular atrophy (SMA) in The New England Journal of Medicine (NEJM). The Part 1 data showed that patients treated with Evrysdi at 12 months demonstrated significant improvement in survival and developmental milestones, including the ability to survive without permanent ventilation, and the ability to sit without support for at least five seconds. Data from the study also demonstrated increased levels of survival motor neuron (SMN) protein, which is critical for maintaining nerve and muscle function.
"The positive data published in The New England Journal of Medicine reinforces the benefits of Evrysdi and substantiates over a decade of work building our splicing platform to develop treatments for patients with diseases of high unmet medical need, like SMA," said Stuart W. Peltz, Ph.D., Chief Executive Officer, PTC Therapeutics. "We believe the platform has broad potential for a large number of target genes across many disease areas."
The table below depicts improvements across Part 1 FIREFISH study after 12 months of treatment*:
Motor milestone achievement | · 7 infants (41%) were able to sit without support for at least five seconds (BSID-III) (n=17) · 9 infants (53%) achieved upright head control (n=17) · 1 infant (6%) was able to stand (HINE-2) (n=17) · 11 infants (52%) had a CHOP-INTEND total score of 40 points or higher (n=21) |
Pulmonary function and swallowing | · 86% (18/21) were able to feed orally, either exclusively or in combination with a feeding tube · 90% (19/21) of infants were alive without permanent ventilation |
Survival | · 90% (19/21) of infants were alive without permanent ventilation · Three infants experienced fatal complications of their disease at one, eight and 13 months after treatment initiation and one infant was withdrawn from the study and passed away 3.5 months after receiving the last dose of study drug. None of these were attributed by the investigator as related to Evrysdi. |
BSID- III - Gross Motor Scale of the Bayley Scale of Infant and Toddler Development – Third Edition |
HINE-2 - Hammersmith Infant Neurological Examination Module 2 |
CHOP-INTEND - Children's Hospital of Philadelphia Infant Test of Neuromuscular Disorders |
*Total n=21: low-dose cohort, n=4, and high-dose cohort, n=17. |
Among the 21 infants enrolled in Part 1 of the FIREFISH study, the most common adverse events included fever (pyrexia; 52%), upper respiratory tract infections (43%), diarrhea (29%), vomiting (24%), cough (24%), pneumonia (19%) and constipation (19%). In total, 24 serious adverse events were reported as of the clinical data cut-off date, with the most common including pneumonia in three infants and respiratory tract infection, viral respiratory tract infection, acute respiratory failure and respiratory distress in two infants each. |
Pharmacodynamic data show infants receiving the recommended dose of Evrysdi had a median 1.9-fold increase from baseline of SMN protein at 12 months of treatment, with blood SMN protein concentration reaching its highest median value of 5.87 ng/ml (n=17; range 2.84 to 8.76) at four weeks, and at 12 months the median value was 5.66 ng/ml (n=15; range 2.66 to 8.60).
FIREFISH is an open-label, two-part, pivotal clinical trial designed to evaluate the safety, tolerability, efficacy, pharmacokinetics (PK) and pharmacodynamics (PD) in infants with type 1 SMA. Part 1 was a dose-escalation study with the primary objective of assessing the safety profile of risdiplam in infants and determining the dose for Part 2. The median duration of treatment was 14.8 months at the time of analysis. The median age at enrollment was 6.7 months and symptom onset between the ages of 28 days to 3 months.
Evrysdi is designed to treat SMA by increasing and sustaining the production of the SMN protein. SMN protein is found throughout the body and is critical for maintaining healthy motor neurons and movement. Roche leads the clinical development of Evrysdi as part of a collaboration with the SMA Foundation and PTC Therapeutics. Evrysdi is marketed in the United States by Genentech, a member of the Roche Group.