No New Issues for Evrysdi Reported in Compassionate Use Program
No new safety signals related to Evrysdi (risdiplam) were documented in a compassionate use program in Germany where more than 100 people with spinal muscular atrophy (SMA) were treated with the oral therapy prior to its approval last year, a new study reports.
“We present the first real-world safety data of [Evrysdi] in patients with SMA in Germany. Our observations indicated no new safety signals under real-world conditions,” the researchers wrote.
The study, “Short-term safety results from compassionate use of risdiplam in patients with spinal muscular atrophy in Germany,” was published in the Orphanet Journal of Rare Diseases. The research was funded by Roche, which markets Evrysdi.
Evrysdi is an oral therapy that works to boost production of the SMN gene whose deficit causes SMA. The therapy was approved in Europe in March 2021 to treat SMA patients ages 2 and older. It has received similar approvals in the U.S. and many other countries worldwide, including Canada.
Prior to achieving regulatory approvals, Roche had opened compassionate use programs in more than 50 countries worldwide, aiming to provide Evrysdi to people with SMA who did not have other treatment options.
Here, researchers reported data from one such program in Germany.
“We report the first real-world data on patient characteristics and short-term safety for risdiplam in clinical practice in Germany,” the team wrote.
The German compassionate use program began enrolling participants in March 2020, and concluded enrollment a year later after Evrysdi was approved. In that time, more than 100 patients were treated across 23 centers — 31 patients with SMA type 1 and 80 with type 2. The average duration of Evrysdi treatment was 5 months for type 1 patients and 3.7 months for those with type 2.
An additional 22 patients also were enrolled, but did not actually start treatment with Evrysdi before the program concluded. Among all the enrolled patients, the average age was 13.1 years for those with type 1 and 27.6 years for those with type 2.
“Although this CUP [compassionate use program] was restricted to patients with SMA1 and SMA2, considerably more and older patients than was initially expected were included into the program, which underlined an unmet medical need for an additional treatment option,” the researchers noted.
“We expect that recently approved oral [Evrysdi], which can be self-administered at home, has significantly reduced this treatment gap,” they added.
Most had used Spinraza
Most of the patients — more than three-quarters of those with type 1, and slightly more than half of those with type 2 — had been treated previously with Spinraza (nusinersen), which was the first disease-modifying treatment approved for SMA.
The vast majority of patients either were not eligible for Spinraza or could not continue with the medication, mainly due to issues with administration: Spinraza is given via an injection into the spine, and many patients had scoliosis or other conditions that posed safety risks with the injection itself or with sedation related to it.
All of the patients were ineligible for treatment with Zolgensma (onasemnogene abeparvovec-xioi), a gene therapy that became available in Germany shortly after the program started, mainly due to unacceptable safety risks.
Safety data reported during this compassionate use program were generally in line with data from clinical trials of Evrysdi. Serious adverse events (safety-related outcomes) were documented in three patients, including one instance of pneumonia in a preschool-aged child with SMA type 1 that was deemed potentially related to Evrysdi. Other serious adverse events were not deemed treatment-related, and none of these events were fatal.
The most common side effects attributed to Evrysdi included diarrhea, nausea, rash, and headache. No treatment-related safety events led patients to stop taking the therapy.
“Generally, the safety data observed in this CUP were in line with the safety profile of risdiplam in ongoing clinical studies,” the researchers concluded.
A major limitation of this analysis, the scientists noted, is that compassionate use programs are designed to provide access to therapies for patients in need, not to collect data — these programs “do not show the rigor, control and close monitoring of clinical trials intending to generate data for the submission of drug applications,” the researchers wrote.
“Despite the limitations of a CUP-based data collection, our observations … indicated no new safety signals under real-world conditions,” they added.