Potential SMA Therapy Ready for a First Clinical Test

posted Jan 23, 2016, 1:42 PM by Patrice Fletcher
January 12, 2016

Roche's RG7916, an SMA2 splicing modifier, entering Phase 1 study after predecessor put on hold

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.

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