Risdiplam Granted EMA’s PRIME Designation for Potential in Spinal Muscular Atrophy

The European Medicines Agency has granted a priority medicines, or PRIME, designation to oral therapy candidate risdiplam to treat spinal muscular atrophy (SMA).

PRIME designation is intended to encourage the development of promising therapies by speeding their evaluation so that the therapies, if proven effective, can be available to patients sooner.

SMA patients have a defective SMN1 gene, which provides instructions for making the SMN protein. Expression of another similar gene, SMN2, also generates the SMN protein, albeit shorter and unstable. Risdiplam, developed by Roche and Genentech in collaboration with PTC Therapeutics and the SMA Foundation, is a once-daily oral treatment designed to boost production of full-length SMN2 mRNA and increase the levels of functional SMN protein.

Increasing research suggests that SMA affects organs beyond the central nervous system (brain and spinal cord). Risdiplam was designed to effectively reach the central nervous system while also being widely distributed throughout the body to increase the production of SMN protein.

“SMA is the leading genetic cause of death in young children, and families and clinicians continue to seek alternative treatment options for this progressively debilitating and life-threatening disease,” Sandra Horning, MD, Roche’s chief medical officer and head of global product development, said in a press release.

“The EMA’s decision to grant PRIME designation recognises the potential of the oral systemic agent risdiplam to deliver clinically meaningful results for patients and address a continuing medical need in SMA,” she added.

The agency’s decision was based on early positive results of two Phase 2/3 clinical trials, called FIREFISH (NCT02913482) and SUNFISH (NCT02908685), which are evaluating the therapeutic benefits of risdiplam in patients with different types of SMA.

Earlier this year, results from the first part of these studies showed that risdiplam treatment increased SMN protein levels among SMA patients. Preliminary functional results from the first part of these trials were presented earlier this month at the Annual Congress of the World Muscle Society in Mendoza, Argentina.

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In the FIREFISH study risdiplam was given once a day to 21 babies from 1 to 7 months old with SMA type 1, the most severe form of the disease. The median age at first dose was 6.7 months, and median treatment duration was 9.5 months.

As of Sept. 7, 19 babies were still alive — two died due to disease progression and therefore were not considered therapy-related. No infant needed permanent ventilation or lost the ability to swallow.

In addition, many of the 14 infants who were treated for eight months achieved several motor milestones — assessed through the Hammersmith Infant Neurological Examination (HINE) Module 2 — such as kicking (50%), sitting with or without support (43%), upright head position (43%), and rolling to the side (29%).

Of the six babies who were able to sit with or without support, three achieved unassisted sitting, something type 1 SMA babies never achieve when considering the natural history of the disease.

Moreover, after eight months of treatment, the median change in the CHOP-INTEND score – a measure of motor skills ranging from zero to 64 points, with zero meaning no response – was 16 points, with 93% of them showing a greater than four-point improvement and 57% having a score higher than 40.

Interim results from the first part of the SUNFISH study, in which 35 patients with SMA type 2 or 3 were randomized to receive risdiplam for at least one year, showed that 19 patients (63.3%) had motor improvements, as shown by a 3.1-point improvement in the Motor Function Measure-32, a validated scale to assess motor function in neuromuscular diseases.

After one year of treatment, the levels of the SMN protein in the blood showed a more than twofold increase.