Date: 2015-04-20
Type of information: Presentation of results at a congress
phase: 1b - 2a
Announcement: presentation of results at the 2015 American Academy of Neurology 67th Annual Meeting
Company: PTC Therapeutics (USA - NJ) SMA Foundation (USA) Roche (Switzerland)
Product: Spinal Muscular Atrophy (SMA) program including motor neuron 2 (SMN2) gene splicing modifier (RG7800)
Action
mechanism: RG7800 is an orally available small molecule being investigated for its ability to selectively modify the splicing of the SMN2 gene, which is present both in healthy individuals and SMA patients, towards the production of full length mRNA. Preclinical studies in animal models of SMA demonstrated an increase in functional full length SMN protein with significant efficacy benefits on survival and motor function.
Disease: spinal muscular atrophy
Therapeutic area: Neuromuscular diseases - Rare diseases - Genetic diseases
Country:
Trial details:
Latest
news: * On April 20, 2015, PTC Therapeutics announced that Phase 1 clinical data from the company's joint development program with Roche and the SMA Foundation in spinal muscular atrophy (SMA) will be presented at the 2015 American Academy of Neurology 67th Annual Meeting. The late-breaking abstract titled "SMN2 splicing modifier RG7800 shows dose-dependent increase of full length SMN2 mRNA in first-in-human study" will be presented as part of the Emerging Science session on April 22, 2015. As previously disclosed, findings from the Phase 1 study indicated that RG7800, an investigational oral therapy for SMA, showed a favorable safety profile and was well tolerated at all dose levels studied. In addition, proof of mechanism was demonstrated by a dose-dependent effect on Survival Motor Neuron 2 (SMN2) splicing towards the production of full length SMN2 mRNA. The Phase 1 study was a single ascending dose, placebo-controlled, double-blind study in 48 healthy volunteers testing single oral doses from 0.5 to 90 mg. * On November 19, 2014, PTC Therapeutics announced that its joint development program in Spinal Muscular Atrophy (SMA) with Roche and the SMA Foundation (SMAF) has started a Phase 1b/2a study in adult and pediatric patients. The placebo-controlled, randomized, multiple-dose study will enroll approximately 48 patients with SMA and investigate the safety and tolerability of an investigational survival of motor neuron 2 (SMN2) gene splicing modifier (RG7800) over 12 weeks. The achievement of this milestone triggers a $10 million payment to PTC from Roche. As previously reported, the Phase 1 single-ascending dose study in healthy volunteers demonstrated that all doses studied were safe, well tolerated and demonstrated a dose-dependent effect on SMN2 splicing as shown by a change in the ratio of full-length SMN2 mRNA to SMN2 mRNA without exon 7 (SMND7), which is interpreted as proof of mechanism in terms of the expected pharmacodynamic effect. The development of RG7800 is being led by Roche and overseen by a joint steering committee with members from Roche, PTC and the SMA Foundation.
* On January 22, 2014, PTC Therapeutics, the SMA Foundation, and Roche have announced that their joint research program in Spinal Muscular Atrophy (SMA) has entered the first stage of clinical development aiming to assess safety and tolerability of an oral compound in healthy volunteers. SMA is caused by a missing or defective SMN1 gene, which results in reduced levels of the survival motor neuron (SMN) protein. Reduced levels of SMN protein lead to dysfunction and death of the neuronal cells, making muscles smaller and weaker over time, and can even result in death in the most severe forms of the disease. The orally available small molecule compounds in the program are designed to target the underlying cause of the disease by increasing SMN protein levels in the nervous system, muscles, and other tissues.
In November 2011, Roche had gained an exclusive worldwide license to the SMA program. The initiation of the clinical development triggers a $7.5 million payment to PTC from Roche.
