information: Presentation of results at a congress
Announcement: presentation of results at the Cure SMA Meeting
Company: PTC Therapeutics (USA - NJ) Roche (Switzerland)
mechanism: 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.
Disease: type 2 and type 3 spinal muscular atrophy (SMA)
area: Rare diseases - Genetic diseases - Neuromuscular diseases
Country: Australia, Canada, Germany, Spain, Sweden, Switzerland, UK, USA
details: SUNFISH is a two-part phase 2 clinical study. Part 1 is a double-blind, placebo-controlled, randomized, exploratory dose-finding study in Type 2/3 pediatric and adult SMA patients. The primary objective of the first part of the study is to evaluate the safety, pharmacokinetics, and pharmacodynamics of RG7916 in patients, and to select the dose for the second part of the study. The pivotal second part is a double-blind, placebo-controlled, randomized, confirmatory study in Type 2/3 SMA patients followed by an open-label extension. The primary objective of the pivotal second part of the study is to evaluate the safety and efficacy of RG7916 compared to placebo. SUNFISH is one of three ongoing clinical trials of RG7916, along with FIREFISH and JEWELFISH. (NCT02908685 )
- • On July 1, 2017, PTC Therapeutics announced the presentation of preliminary clinical data from the company's joint development program with Roche and the SMA Foundation in spinal muscular atrophy (SMA) at the Cure SMA Meeting in Orlando. Preliminary results from an early analysis of Part 1 of the Phase 2 SUNFISH trial evaluating oral RG7916, a small molecule modifier of Survival Mo tor Neuron 2 (SMN2) splicing, were highlighted in an oral presentation titled "Clinical Studies of RG7916 in Patients with Spinal Muscular Atrophy: Study Update."
- Preliminary results from an early analysis from the ongoing Part 1 of the RG7916 SUNFISH study in Type 2/3 SMA patients demonstrated a dose-dependent increase in SMN2 full length/?7 mRNA ratio of ~ 400% versus baseline, as measured in whole blood. These results provided proof of mechanism for oral small molecule SMN2 splicing modifiers. No drug-related adverse events leading to withdrawal have been observed to date for RG7916.
- • On October 20, 2016, PTC Therapeutics announced that its joint development program in Spinal Muscular Atrophy (SMA) with Roche and the SMA Foundation (SMAF) initiated a Phase 2 study in pediatric and adult Type 2/3 SMA patients. The study, named SUNFISH, is a two-part study investigating the safety, tolerability and efficacy of RG7916, an oral small molecule survival motor neuron 2 (SMN2) splicing modifier. The first part of the study will evaluate safety and tolerability through escalating doses of RG7916. After dose selection, the study will transition into the pivotal second part evaluating the efficacy of RG7916. Initiation of the pivotal second part of the study is expected to begin in 2017 and will trigger a $20 million milestone payment to PTC from Roche. A similarly designed two-part study to evaluate RG7916 in Type I SMA patients is expected to begin in the coming months.
- A trial in Type I SMA patients, 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.