- Roche and PTC Therapeutics' risdiplam helped babies with the most severe form of spinal muscular atrophy achieve important motor milestones and kept them from losing the ability to swallow or needing permanent ventilation, according to data from an early-stage trial. The experimental drug is an oral agent that modulates gene expression to help the body produce a protein that preserves motor neurons.
- Risdiplam is advancing in an increasingly competitive space, with Biogen's Spinraza already on the market and Novartis' gene therapy Zolgensma due for a Food and Drug Administration decision any day. The 41% of patients in the risdiplam Type 1 SMA trial who sat without assistance makes the drug look at least as good as Sprinraza, although direct comparisons are difficult.
- Physicians who specialize in treating SMA patients must now consider which therapy might offer the best chance of improving outcomes. Novartis executives have argued that "there's no scientific rationale" for combinations on a Zolgensma backbone.
The biopharma sector is changing the severest form of SMA from a fatal disease to a chronic condition. Spinraza (nusinersen), which like risdiplam modulates genetic expression to help preserve the motor neurons, premiered in 2016 and helped babies with Type 1 survive, albeit with some disabilities.
The next agent is expected to be Zolgensma (onasemnogene abeparvovec), but hot on its heels is risdiplam, which could have an advantage in its oral dosing route.
At the American Academy of Neurology meeting, Roche and partner PTC Therapeutics released updated data Tuesday from two studies, the FIREFISH trial in Type 1 infants and the SUNFISH trial in older patients with the less severe Type 2.
FIREFISH was aimed at finding a therapeutic dose, which 17 patients received. Of those, nine achieved full head control, seven sat without assistance for at least five seconds, and one stood with support. Two of the patients in this group died because of disease complications.
Using a measure of motor control tests called CHOP-INTEND, the FIREFISH patients receiving the therapeutic dose improved their scores by a little more than 17 points. That compares favorably to Spinraza and Zolgensma, which saw improvements of 15 and 25 points, respectively.
"These are really impressive milestones for what is a devastating disease.," Susan Begelman, vice president of neurology at Roche's Genentech subsidiary, said in an interview with BioPharma Dive.
The SUNFISH trial in older patients with Type 2 or 3, aged from 2 to 25 years, found signs of motor improvement, although the data from the trial is not mature enough to show statistical significance because patients have not been in the trial long enough.
However, Roche released exploratory data showing that of patients who have completed all clinic visits through one year, 71% of those age 2 to 11 improved at least three points on a test called MFM32, along with 42% of those aged 12-25 years.
As an oral agent, risdiplam may be preferable to the spinal fluid injections of Sprinraza and some Zolgensma patients, Begelman said. "Many patients with SMA have scoliosis or spinal fusions," she said.
Roche plans on submitting risdiplam for FDA approval in the second half of 2019. If both Zolgensma and risdiplam are licensed and join Spinraza on the market, specialists will need to look closely at trial data to consider which agent is most appropriate for specific patients — such as those with spinal complications.
Whether to use them in combination will be another question, as patients in Zolgensma trials have been reported to have subsequently sought treatment with Spinraza.
"It’s going to take some time to determine how all these treatments will be used," Begelman said. "It certainly is a question that is coming up."