Though a rare condition, the debilitating wasting disease spinal muscular atrophy (SMA) is gaining a large biopharma interest (and price tags in the millions of dollars), and Roche and partner PTC Therapeutics are the latest companies to show their hand in improving kids’ ability to move with the genetic disorder.
At this year’s American Academy of Neurology (AAN) Annual Meeting, Roche and biotech PTC (alongside the SMA Foundation) posted the latest data from their SMA drug risdiplam, a small molecule SMN2 splicing modifier, from the dose-finding Part 1 of the pivotal Firefish trial, which showed infants with Type 1 SMA (the most common of the four types of the disease) achieved “key motor milestones after one year of treatment.”
Among the 17 infants who received the dose selected for the confirmatory Part 2 of the study, seven (41.2%) were able to sit without support for at least five seconds, assessed by the Gross Motor Scale of the Bayley Scales of Infant and Toddler Development.
On top of this, 11 (64.7%) were able to sit (with or without support) while nine (52.9%) achieved upright head control after 12 months of treatment as assessed by the Hammersmith Infant Neurological Examination Module 2. One child hit the milestone of standing by this 12-month time point.
Part 1 of the Firefish test also assessed motor function with the Children’s Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP INTEND), a scale used for infants with Type 1 SMA.
This showed 58.8% in the dosed group achieved a total score of 40 points or more, with median change from baseline to month 12 being 17.5 points. The max score was 57 points after 12 months of treatment, increasing from a maximum of 49 points after eight months.
Three children died as a result of the disease at one, eight and 13 months of treatment, but Roche says this was not due to its drug. “No infant has lost the ability to swallow during the study, and no infant has required tracheostomy or permanent ventilation,” the Swiss major added.
Roche also posted new data for less common Types 2 and 3 out of the Sunfish trial in older patients aged 2 to 25.
An “exploratory efficacy analysis” of Part 1 of this test, which was in 51 patients, looked at motor function using the Motor Function Measure-32 (MFM32) scale: Among the patients for which the MFM32 scale has been completed at all visits up to month 12 (43 patients), 58% saw an improvement of at least three points on the scale from baseline, including 71% among patients 2 to 11 years old and 42% aged 12 to 25 years.
“While Part 1 of the Sunfish study was not designed or powered to detect efficacy, the change from baseline in total MFM32 score is the primary efficacy endpoint in the ongoing Part 2 (which has 180 patients) of the trial,” the company said.
The confirmatory Part 2 portions of both tests have now completed enrollment and start their primary efficacy analyses in the fourth quarter of 2019 and the first quarter of 2020, respectively, Roche said. It will be using these latest data, alongside its older updates, toward regulatory filings with both FDA and EMA “during the second half of 2019,” it added.
This will see it rival Biogen and Ionis’ SMA drug Spinraza as well as Novartis’ gene therapy for the condition, Zolgensma, which is expected to get the FDA nod any day now and also posted new data at AAN this week.
Analysts at SVB Leerink said of the latest data from Roche: “We forecast $600 million worldwide peak risdiplam sales at 80% probability for CHF3/share (1%) NPV. Our recent SMA physician survey suggests this could be far too conservative, with 29%-34% of patients anticipated to be treated with this convenient oral therapy 3-5 years from now.”
It added that the Type 2-3 SMA data “also demonstrated encouraging initial efficacy in a broad population,” and that the Type 1 results were “well beyond those expected by disease natural history,” although it will need to best Spinraza and Zolgensma as well as beat out natural history if it wants to take market share.