Roche Begins Enrolling SMA Type 1 Infants in Phase 2 Trial of Therapy Targeting SMN2

Roche has started enrolling infants with spinal muscular atrophy (SMA) type 1 in a Phase 2 trial of its SMN2-targeting therapy RO7034067, following positive early results from a similar and ongoing study of the compound in older children with type 2 and 3 SMA.

The FIREFISH trial (NCT02913482), now underway in the United States, will also include infants between 1 and 7 months of age at select sites in Europe, according to a press release issued by the nonprofit organization Cure SMA. All sites are recruiting for this study.

Scientists presented data from the other Phase 2 trial, SUNFISH (NCT02908685) — taking place in Europe and likely to begin recruiting children and young adults in the United States, Canada and Australia — at the Cure SMA Meeting in early July. These preliminary results showed that the treatment significantly boosted the production of SMN from the SMN2 “backup” gene.

Researchers have not yet analyzed if this increase will lead to improvements or slower disease progression.

Developed in collaboration with PTC Therapeutics and the SMA Foundation, RO7034067 — also known as RG7916 — is a pill that intends to correct the splicing of SMN2.

A gene often holds stretches of DNA that must be cut out, with the remaining coding parts, called exons, stitched together again. The process is called splicing. When the SMN2 gene is stitched together, it often lacks one of the coding parts, rendering the protein unable to work normally. So-called splicing modifiers make sure that the missing part is included, so that more functional SMN protein is made.

FIREFISH, which will recruit about 50 infants, is an open-label study in which all participants get the active treatment. Like the study in type 2 and 3 patients, the infant trial will also consist of two parts.

The first part intends to find the optimal dose of RO7034067 and will run for four weeks. The second part will run for 24 months, during which researchers will analyze the drug’s safety and its properties in this patient group. They will also see if the treatment affects the course of SMA or its symptoms. Its primary outcome is the proportion of infants sitting without support after 12 months of treatment.

Roche will also explore the treatment in a Phase 2 trial called JEWELFISH (NCT03032172), in which SMA type 2 or 3 patients  previously treated with an SMN2-targeting therapy (other than RO7034067) can participate. Both trials are also recruiting participants.