Roche, PTC Therapeutics, and the SMA Foundation are currently researching an investigational therapy, RG7916,  for the treatment of spinal muscular atrophy (SMA).

How RG7916 works

RG7916 is a splicing modifier, which means it is designed to shift the pre-mRNA splicing toward the production of full-length SMN mRNA

Clinical trials for RG7916 

A Phase 1 study (NCT02633709) investigating the safety, tolerability, pharmacokinetics (how the drug moves in the body), and pharmacodynamics (the drug’s effect in the body) of increasing doses of RG7916 in healthy volunteers was completed in August 2016. The study’s goal was to assess RG7916’s safety and tolerability in these volunteers, with data collected helping to determine the optimal dose for people with SMA.

The Phase 2 Firefish study (NCT02913482) evaluating the effectiveness of RG7916 in infants with type 1 SMA is currently recruiting participants.

The study will be divided into two parts. The first part will be exploratory, where participants will receive multiple ascending doses of RG7916, administered orally once daily for four weeks followed by an open-label extension phase.

The second part will be confirmatory, where participants will receive RG7916 administered orally at the maximum tolerated dose of the first part, with treatments continuing up to 24 months. The primary endpoint will be the percentage of infants who are able to sit without support at 12 months, and secondary endpoints will range from the percentage of participants with adverse events to blood biomarkers and a number of milestones related to child development. The estimated primary completion date of the trial is April 2019.

A Phase 2 study called Sunfish (NCT02908685) to assess the safety, tolerability and effectiveness of RG7916 in type 2 and 3 SMA is also currently recruiting participants.

There will be two groups in this trial. The first will include participants ages 12-25 years old who will receive either RG7916 or placebo for 12 weeks, and then for up to 24 months, at the dose decided in the first 12 weeks. At the end of the 24-month period, the participants will be offered the opportunity to enter an open-label extension study.

The second group will include children ages 2-11 who will follow the same treatment as the former group. The primary endpoint will be the change in the total motor function after 12 months, and the secondary endpoint will include blood biomarkers and measures in different motor functions. The estimated primary completion date of this trial is April 2019.

A Phase 2 study called Jewelfish (NCT03032172) evaluating RG7916 in adults and children with SMA is currently recruiting participants. Participants will receive multiple doses of RG7916 orally once daily for 24 months. Primary endpoints will be the percentage of participants with adverse or serious events, with suicidal ideation or behaviors, and with clinically significant changes in ophthalmological assessments and blood biomarkers. The estimated primary completion date of this trial is January 2020.

In January 2017, PTC announced that RG7916 was granted orphan drug status from the U.S. Food and Administration (FDA). The purpose of this designation is to promote the development of drugs that may help patients of rare diseases. The benefits to pharmaceutical companies of this designation include grant funding opportunities, clinical trial cost and tax advantages, FDA user-fee benefits, FDA guidance during the drug approval process.

Other details

Along with RG7916, another drug, RG7800, was also under development for the treatment of SMA. That drug was in a Phase 1 clinical trial (NCT02240355, known as MOONFISH) but it was terminated after an unexpected toxicology finding was identified in an animal study exploring long-term treatment.

Roche is developing RG7916 with a joint steering committee whose members include PTC, Roche, and the SMA Foundation.

Read the latest news about RG7916 at SMA News Today and follow the latest developments for all experimental spinal muscular atrophy treatments on the SMA Therapy Tracker.

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