Weeks after FDA delay, Roche, PTC unveil another batch of positive risdiplam data in severe SMA patients
While the FDA has decided it needs another quarter to review Roche and PTC Therapeutics’ oral SMA therapy, its makers are reporting a steady drumbeat of new positive data. On Tuesday, the companies unveiled one-year data in patients with the most severe form of the disease from a key trial.
The FDA is set to make its decision on the therapy, risdiplam, by August. It is expected to compete with Biogen’s Spinraza and Novartis’ Zolgensma.
The data were from Part 2 of the FIREFISH trial evaluating risdiplam in 41 infants aged 1 – 7 months old with symptomatic type 1 SMA. The study met the main goal — with 29% of infants sitting without support for five seconds by month 12. Typically, no infants hit this milestone in the natural history of type 1 SMA.
Two pivotal studies constitute risdiplam’s marketing application. FIREFISH is an open-label trial in infants with type 1 SMA, while SUNFISH is placebo-controlled and recruited patients aged 2 to 25 years with types 2 or 3 SMA. Both contain two parts: The first portion is used to determine the optimal dose and assess the safety, while the latter is employed to confirm efficacy.
Data from FIREFISH Part 2 also showed 18 infants were able to hold their head upright, 13 were able to roll to the side and 2 infants were able to stand with support. In an exploratory endpoint, 95% of infants who were alive at 12 months (36/38) maintained the ability to swallow and 89% (34/38) were able to feed orally.
The drug’s safety profile was consistent with previous studies.
“We believe that this efficacy compares favorably to the data from Biogen’s ENDEAR study of Spinraza in Type 1 SMA, which showed that ~84% were alive after 1 year of treatment and the event free survival rate was ~55%,” Baird analyst Brian Skorney wrote in a note.
“While cross-trial comparisons are always difficult, we believe that the strong data Part 2 of the FIREFISH study of risdiplam should lead to rapid uptake of this medication once it is approved, which would come at the detriment of Spinraza as patients are likely to switch to the more efficacious medication.”
Biogen’s Spinraza, an antisense oligonucleotide, is injected in the spine every four months following initial loading doses. Novartis’ Zolgensma, a gene-therapy, is designed to be a one-shot cure, while risdiplam is a daily oral treatment, engineered to work by tweaking how the SMN2 gene is spliced, which raises functional SMN protein levels in both the central nervous system and peripheral tissues.
SMA is rare, affecting 1 per 8,000 to 10,000 people globally, but represents a lucrative battleground for these drugmakers. Spinraza, launched in late 2016, carries a list price of $750,000 for the first year and $375,000 annually thereafter. Zolgensma — only approved for patients under the age of 2 — caused sticker shock with its $2.1 million price tag and the inevitable pushback from payers, although Novartis has emphasized that its five-year installment plan and curative potential makes it worth it.
With Roche’s plan to make risdiplam cheaper than Spinraza, the appeal of oral administration could make the drug an even bigger threat to the Spinraza franchise — which generated nearly $2.1 billion last year — compared to the world’s most expensive therapy, Zolgensma.
“Given the dynamics surrounding COVID-19, and the anticipated shift toward telemedicine and minimizing in-person interaction with healthcare providers, we believe the competitive advantage of being an oral therapy that can be given at home will be even more pronounced and could lead to the rapid uptake of risdiplam should the medication gain approval by the August 24th PDUFA,” Skorney added.
Earlier this month, the FDA said it needed another three months to review additional data on the drug submitted by its makers.