Potential SMA Therapy Ready for a First Clinical Test

Roche recently announced that a new investigational medicine for the treatment of spinal muscular atrophy (SMA) — RG7916 — will soon advance to its first clinical trial. The study will provide information on the safety and tolerability, and investigate the pharmacokinetics (absorption, distribution, metabolism and excretion) of RG7916 in healthy individuals.

In April 2015, the Moonfish clinical trial investigating another drug sharing the same mechanism, called RG7800, was placed on hold as a precautionary measure. An animal study of prolonged exposure to high doses of the drug showed unfavorable results, and the trial remains on hold until the investigation of the findings is complete.

Meanwhile, Roche continued to work on RG7916. Both drugs are SMN2 splicing modifiers — targeting the SMN2 gene, which produces only low levels of the SMN protein due to the splicing of the messenger RNA. Typically, people have up to two copies of the SMN2 gene in each cell. In some cases, individuals have three or more copies. In those with spinal muscular atrophy, additional copies of the SMN2 gene are associated with a milder course of the disorder.

Splicing modifiers can shift the balance of SMN2 splicing from the production of the nonfunctional short-form, toward the production of full-length functional SMN with the ability to rescue the phenotype. Indeed, a study published in the journal Science in 2014 showed that SMN2 splicing modifiers can improve motor function and longevity in a mouse model of spinal muscular atrophy.

Data from the Phase 1 trial will be used to compare RG7916 and RG7800, to form a foundation on which to base decisions regarding the advancement of the program. Roche points out that the new drug has different characteristics relative to RG7800, which may influence how the medicine interacts with the body.

Roche also said the trial will employ Itraconazole, an approved drug, as a tool to help understand the metabolism, or break-down, of RG7916 in people. Itraconazole is an antifungal agent known to interact with a large number of drugs.

Roche is planning to post study updates by mid-2016. The investigation of RG7916 is being done in collaboration with Roche partners PTC Therapeutics and the SMA Foundation.

The announcement, formulated in a letter to the SMA community, ended with a direct message to SMA patients: “Our commitment to helping the SMA community remains strong as we continue to pursue new medicines for the treatment of SMA. In collaboration with our partners, PTC Therapeutics, and the SMA Foundation, we would like to thank you for sharing your experience of living with SMA; you inspire us every day.”