information: Presentation of results at a congress
Announcement: presentation of results at the 23rd International Annual Congress of the World Muscle Society
Company: PTC Therapeutics (USA - NJ) Roche (Switzerland)
Product: risdiplam - RG7916/RO7034067
- splicing modifier. RG7916 directly targets the underlying molecular deficiency of SMA by modulating SMN2 splicing to increase expression of stable full-length SMN2 mRNA from the SMN2 gene. A healthy volunteer study was recently completed and the preliminary results demonstrate that RG7916 increased the production of full-length SMN2 mRNA further demonstrating proof of mechanism for oral small molecule SMN2 splicing modifiers. RG7916 was also well tolerated.
- In November 2011, Roche gained an exclusive worldwide license to the PTC/SMA Foundation SMN2 alternative splicing program. The development of these compounds is being executed by Roche and overseen by a joint steering committee with members from PTC, Roche, and the SMA Foundation.
Disease: type 1spinal muscular atrophy (SMA)
area: Rare diseases - Genetic diseases - Neuromuscular diseases
Country: France, Italy, United States
- FIREFISH is a two-part study. Part one is an open-label, dose escalation study in at least 8 infants for a minimum of 4 weeks. The primary objective of part one is to assess the safety profile of RG7916 in infants and determine the dose for part two.
- Part two is an open-label, single-arm study in approximately 40 infants with Type I SMA for 24 months, followed by an open-label extension. The primary objective of part two is to assess the efficacy of RG7916 at the selected dose over a 12-month treatment period.
- The SMA program was initially developed by PTC Therapeutics in partnership with the SMA Foundation in 2006 to accelerate the development of a treatment for SMA. (NCT02913482)
- • On October 3, 2018, Roche announced interim clinical data from the dose-finding parts of the pivotal FIREFISH and SUNFISH studies investigating risdiplam (RG7916) in spinal muscular atrophy (SMA). In the FIREFISH study in Type 1 SMA, six out of 14 infants (43 percent) were able to sit (with or without support), including three (21 percent) who achieved unassisted stable sitting after eight months of treatment. In addition, four infants (29 percent) demonstrated rolling to the side; seven (50 percent) kicking and six (43 percent) achieved upright head control. These milestones were assessed according to the Hammersmith Infant Neurological Examination (HINE) Module 2 and are key secondary endpoints in the confirmatory part of FIREFISH.
- The data were presented at the 23rd International Annual Congress of the World Muscle Society in Mendoza, Argentina. Roche and Genentech are leading the clinical development of risdiplam, an oral SMN2 splicing modifier, as part of a collaboration with the SMA Foundation and PTC Therapeutics.
- Updated analyses of the Children's Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP-INTEND), a scale developed to assess motor function in infants with Type 1 SMA, demonstrated that eight out of 14 infants in FIREFISH (57 percent) achieved a score of 40 or above at their eight-month visit. Typically, an infant with Type 1 SMA does not demonstrate any motor improvement and can decline during this time period. The median CHOP-INTEND scores increased over time (37.5 at 6 months [n=20] compared to 41.5 at eight months [n=14]). The median age at first dose in FIREFISH was 6.7 months and median treatment duration was 9.5 months. Nineteen out of 21 infants enrolled (90 percent) remain alive with two having discontinued due to the fatal progression of their disease. Three patients are now over 24 months old. No infant has required a tracheostomy or permanent ventilation since study initiation, and no infant has lost the ability to swallow. The most common adverse events were fever (pyrexia; 52.4 percent), diarrhea (26.8 percent), upper respiratory tract infections (19 percent), ear infections (14.3 percent), pneumonia (14.3 percent), constipation (14.3 percent), vomiting (14.3 percent), cough (14.3 percent) and upper respiratory tract inflammation (14.3 percent). Follow-up is ongoing for the confirmatory Part 2 portions of both the FIREFISH and SUNFISH studies.• On January 5, 2017, PTC Therapeutics announced that its joint development program in Spinal Muscular Atrophy (SMA) with Roche and the SMA Foundation (SMAF) initiated a clinical study in infants with Type I SMA. The study, named FIREFISH, will investigate the safety, tolerability and efficacy of RG7916 in babies aged 1 to 7 months.
- Another trial in childhood onset (Type II/III) SMA patients, SUNFISH, is currently enrolling the dose escalation portion of the study. Commencement of the pivotal portion of either study will trigger a $20 million milestone payment to PTC from Roche.
- • On October 20, 2016, PTC Therapeutics announced that a trial in Type I SMA patients, named FIREFISH, is planned to initiate in the coming months. FIREFISH is also planned to be a two-part study. The first part is an open-label, dose-escalation study in at least eight infants for a minimum of four weeks. The primary objective of part one of the study is to assess the safety profile of RG7916 in infants and determine the dose for part two. The second part of FIREFISH is expected to be an open-label, single-arm study in approximately 40 infants with Type I SMA for 24 months, followed by an open-label extension. The primary objective of the second part of the study will be to assess the efficacy of RG7916 at the selected dose after 12 months of treatment.