Roche has positive clinical data on its risdiplam candidate in spinal muscular atrophy (SMA), suggesting it could add to the emerging treatment options for the devastating genetic disease.
Risdiplam – which Roche licenses from PTC Therapeutics – is a small molecule that targets and encourages the SMN2 gene to produce a greater amount of functional SMN protein, which is lacking in people with SMA and leads to progressive neuromuscular degeneration.
Data on its efficacy has emerged from two phase 2/3 trials – FIREFISH and SUNFISH – in type 1 and types 2 and 3 SMA, respectively, have shown that the therapy can help the development of motor function in infants with the disease.
If all goes according to plan the drug could became an oral alternative to Biogen’s injectable Spinraza (nusinersen), the first and only approved therapy for SMA which has been available to patients since 2016 and looks set to top $1bn in sales this year.
In the open-label FIREFISH study, six out of 14 infants treated for eight months with risdiplam were able to sit upright – three of them with no support which is rare in untreated type 1 SMA – and the same number also achieved upright head control.
Meanwhile, the placebo-controlled SUNFISH trial in older children and young adults 63% of patients showed a three point or greater improvement on the Motor Function Measure (MFM) scale after a year, which Roche said was a clinically significant improvement.
Sandra Horning, Roche’s chief medical officer, said the company is “highly encouraged” by the data, which show infants treated with risdiplam “surviving and achieving developmental milestones beyond the natural history of this devastating disease.”
“SMA therapies that produce a sustained increase in SMN protein…may provide comprehensive benefits to people diagnosed with SMA, and we look forward to sharing additional data on risdiplam as the clinical program progresses,” she added.
Roche is also moving ahead with two more studies to further explore how risdiplam might be used in SMA. JEWELFISH is enrolling people aged 12-60 with types 2 or 3 SMA who have been previously treated with Spinraza, while RAINBOWFISH will get underway next year in pre-symptomatic SMA patients.
The commercial potential of both Spinraza and risdiplam could however be short-lived if a gene therapy for SMA – which aims to treat the disease by the one-off administration of a gene coding for SMN – moves quickly through the regulatory process.
Earlier this year, US biotech AveXis revealed data for its gene therapy AVXS-101, showing neuromuscular improvements in 15 symptomatic type 1 SMA patients who were all still alive at 24 months of age without the need for permanent ventilation. The data has been deemed sufficient to support a filing with the US FDA, which is due before the end of the year.
Novartis will be banking on a successful outcome for the AVX-101 programme, after agreeing an $8.7bn takeover of AveXis earlier this year.