Roche/PTC edge closer to disrupting market for SMA rivals Biogen and Novartis with more positive data
Roche and partner PTC Therapeutics have broken out detailed positive data backing their spinal muscular atrophy therapy, which is expected to have a good shot at eclipsing Spinraza’s market leadership.
The FDA is set to make its decision on the therapy, risdiplam, by May 24. If approved — the drug is expected to generate between $2 billion and $3 billion in peak sales — and compete with Biogen’s first-to-market Spinraza and Novartis’ most-expensive-drug-in-the-world Zolgensma.
On Thursday, the companies reported detailed data from the SUNFISH trial, which tested risdiplam against a placebo in 180 patients aged 2-25 years with type 2 and 3 SMA, a rare genetic muscle-wasting disease. Most patients in the trial were older, and a relatively more severe form of the disease. The main goal of the study — which was met — was the change in motor function after one year. Roche initially announced the primary endpoint had been met last November.
The total mean change in patients receiving risdiplam was significantly higher than placebo (1.55 point mean difference; p=0.0156). As expected, the strongest responses versus placebo were observed in the youngest patients aged between 2 and 5 years (78.1% versus 52.9% achieving ≥3 point increase).
It is hard to compute the clinical meaningfulness of risdiplam based on absolute 1.55 mean point reduction, even though statistical significance was hit, SunTrust Robinson Humphrey analyst Robyn Karnauskas wrote in a note.
PTC management has previously suggested that a 2-point difference would be clinically meaningful using the Motor Function Measure scale (MFM-32) scale, but since the mean point difference was 1.55, clinical meaningfulness may not be so evident at first blush, she said.
These results supplement positive data from 41 patient-FIREFISH study, which tested risdiplam in patients aged 1-7 months with type 1 SMA.
Risdiplam is strategically positioned to have strong uptake in the type 2/3 SMA population, Credit Suisse’s Martin Auster wrote in a recent note. “While we expect Zolgensma to capture the vast majority of the incidence Type 1/2 SMA population, we anticipate risdiplam will emerge as the dominant therapy for older SMA patients.”
Biogen secured the first-ever SMA approval and has since been dosed in over 9,300 patients. However, comparing Biogen’s data to the Roche/PTC results in SMA type 2/3 patients is difficult given the primary endpoints are different in the two trials, in addition to different enrollment criteria.
“While the impact of Novartis’ Zolgensma has been relatively muted, we think that the likely approval and launch of risdiplam could impact Biogen’s Spinraza franchise,” Credit Suisse’s Evan Seigerman wrote in a recent note. “We also think that Roche could price risdiplam below Spinraza to help encourage use – especially in T2 or T3 patients.”
Spinraza, an antisense oligonucleotide, is injected in the spine every four months following initial loading doses. 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.
“While there are already 2 efficacious products approved for SMA in the US, (Roche) management…see a very large opportunity given the convenient oral formulation of risdiplam, number of patients not eligible for gene therapy, and small upfront price compared to gene therapy and oligonucleotide competitors,” SVB Leerink analysts wrote in a recent note.