U.S. Food and Drug Administration (FDA) approves the first oral medicine for the treatment of Spinal Muscular Atrophy (SMA), Genentech’s (a subsidiary of Roche) Evrysdi™ (risdiplam), in adults and children of 2 months and older. SMA is a genetic disease affecting a person’s motor skills, caused due to lack of neural stimulation of the muscles. The most common form of SMA is chromosome 5 SMA, caused due to genetic mutation or flaw in chromosome 5 in a gene SMNI, a protein called Survival motor neuron (SMN) Pivotal in gene expressions of neurons. The age of onset determines the severity of SMA, Type 1 being the most severe generally seen in infants and children displaying symptoms by birth and Type 4 being the least. Evrysdi improved the motor functions in individuals with varying severity and across different ages. It is a survival of motor neuron 2 (SMN2) splicing modifier that helps increase SMN protein found to be deficient in SMA patients. This oral, take home treatment becomes especially essential in times like these when pandemic makes commute risky.
This approval follows a Priority review granted by FDA in November, 2019 and Roche’s announcement of 2-year data of Part-1 of its pivotal clinical trial, SUNFISH in people aged 2- 25 years. The trial demonstrated an improvement in the motor skill of infants and adults being treated with Evrysdi, which helped infants survive without permanent ventilation and enabled them to sit without support for at least 5 seconds. This is an important milestone on progress not seen during the natural course of the disease. The liquid dosage administered is weight dependent, I.e., mg per kg.
The results of clinical trials SUNFISH and FIREFISH showed promise as they studied the safety, tolerability, pharmacokinetics, pharmacodynamics, and efficacy of Evrysdi. FIRESFISH was an open label Two-part study in patients aged 1 to 7 months with Type 1 SMA. It demonstrated 41% infants (7/17) were able to sit without support for 5 seconds measured by Bayley Scales of Infant and Toddler Development Third Edition (BSID-III) motor scale along with 90% (19/21) and 81% (17/21) of patients surviving without permanent ventilation and crossing the 12- and 24-month mark respectively. SUNFISH a two-part placebo-controlled multicenter Trial in patients aged 2-25 years with Type 2 and Type 3 SMA saw a significant improvement in the motor functions of those individuals administered with Evrysdi and those given placebo, this was measured by a change from baseline in the Motor Function Measure-32 (MFM-32) total score. More trials are underway, JEWELFISH and RAINBOWFISH, to study the effects of evrysdi based on various criteria. The clinical trial development was in collaboration with SMA Foundation and PTC Therapeutics.
Evrysdi is the third disease-modifying treatment to be approved for SMA. It will commercially challenge Biogen’s Spinraza, approved in 2016 and Novatis’ Zolgensma approved last year. Roche’s price though dependent on a patient’s weight is capped at USD 340,000 per year once the patient reaches 44 pounds. This price is relatively low when pitted against Spinraza ’s list price which is USD 750,000 in the first year and USD 375,000 per year consecutively and Zolgensma’s USD 2.1 million One-time administration. Market share threat is highest for Biogen’s Spinraza that clocked USD 2.1 billion sales last year vs Zolgensma’s USD 361. While Zolengsma is administered once to infants aged less 2 years, Spinraza and Evrysdi are indicated for similar age populations. The oral administration is an added advantage that pits Roche competitively in this high value opportunity. This advantage is especially relevant in the content pandemic context where at home administration will be very valuable. Roche has also filed for approval in Russia, Brazil, Chile, China, Indonesia, South Korea, and Taiwan.