Roche Reports Positive Two-Year Data for Risdiplam in Infants, Children, and Adults with Spinal Muscular Atrophy

Recently, Genentech, a member of the Roche Group, announced positive data from Part 1 of the pivotal SUNFISH trial, which evaluated two years of risdiplam treatment in patients aged 2–25 years with type 2 or type 3 spinal muscular atrophy (SMA). Results from exploratory efficacy analyses demonstrated that 24 months of risdiplam treatment led to significant improvements in motor function compared with natural history data. Furthermore, 12-month preliminary data from the JEWELFISH trial, which enrolled patients aged 6 months to 60 years with various types of SMA who had previously received treatment, showed rapid and sustained increases in survival motor neuron (SMN) protein levels following risdiplam treatment.

SUNFISH is a global study (n=231) in pediatric and adult patients with spinal muscular atrophy (SMA), comprising two parts. Part 1 (n=51) was primarily designed to determine the dose and included a broad patient population, ranging from non-sitters to ambulatory patients, as well as those with scoliosis or joint contractures. This exploratory efficacy analysis assessed motor function using the Motor Function Measure (MFM) scale.

Weighted analyses comparing the data with a reliable natural history comparator cohort demonstrated a substantial overall change from baseline in MFM scores at Month 24 in patients treated with risdiplam (3.99-point difference [95% CI: 2.34, 5.65]; p < 0.0001). Compared with placebo, patients treated with risdiplam also showed a statistically significant improvement from baseline in the total MFM-32 score (mean difference of 1.55 points; p = 0.0156). Even small changes in motor function can result in meaningful differences in patients’ daily lives.

The results also showed that four weeks of risdiplam treatment doubled the average levels of SMN protein in patients’ blood, with this increase sustained for at least 24 months. These findings are consistent with the 12-month results reported previously for ambulatory patients in Part 2 of the pivotal SUNFISH study.

The most common adverse events in Part 1 of the SUNFISH study were fever (55%), cough (35%), vomiting (33%), upper respiratory tract infection (31%), common cold (nasopharyngitis, 24%), and sore throat (oropharyngeal pain, 22%). Among the 51 patients treated with risdiplam, the most common serious adverse event was pneumonia. To date, no treatment-related safety findings have led to discontinuation of therapy.

Furthermore, enrollment in the JEWELFISH study (n=174) has been completed to evaluate the safety and pharmacodynamic data of risdiplam in patients with spinal muscular atrophy (SMA) who had previously received treatment. Among these patients, 76 had been treated with nusinersen (SPINRAZA), 14 with onasemnogene abeparvovec (Zolgensma), and the remaining 83 patients received risdiplam. After 12 months of risdiplam treatment, a two-fold increase in SMN protein levels relative to baseline was observed in patients (n=18).

Compared with untreated patients, early safety assessments demonstrated a consistent safety profile. The most common adverse events were upper respiratory tract infection (13%), headache (12%), fever (8%), diarrhea (8%), nasopharyngitis (7%), and nausea (7%). No drug-related safety findings led to discontinuation from the JEWELFISH trial, and the overall adverse event profile was similar to that observed in patients not receiving SMA-targeted therapy in risdiplam trials.

Spinal Muscular Atrophy (SMA) is a hereditary, progressive neuromuscular disease that can lead to devastating muscle atrophy and disease-related complications. It is the most common genetic cause of infant mortality and one of the most prevalent rare diseases, affecting approximately 1 in every 11,000 live births. Patients with Type 1 SMA typically do not survive beyond the age of two, whereas those with milder forms, such as Type 2 and Type 3, may have longer survival times. However, even the milder forms of the disease are associated with mobility impairment, respiratory infections, and mortality.

Although multiple therapies for spinal muscular atrophy (SMA) are currently available on the market, there remains a substantial unmet need in this field. Spinraza, the first globally approved SMA therapy launched in 2016, achieved total sales revenue of USD 2.097 billion in 2019, representing a 22% year-over-year increase, with an annual treatment cost of USD 750,000. Zolgensma, the second SMA therapy, was launched in May 2019 and generated USD 361 million in sales during its first three quarters on the market. Roche’s Risdiplam has demonstrated positive efficacy data in patients who had previously received these two therapies, which may further enhance Risdiplam’s advantages and competitiveness in the market.

Reference Source: Genentech Announces 2-Year Risdiplam Data From SUNFISH and New Data From JEWELFISH in Infants, Children and Adults With Spinal Muscular Atrophy (SMA)