The US Food and Drug Administration has approved an oral drug for treating spinal muscular atrophy (SMA), developed by PTC Therapeutics and Roche’s Genentech unit. Evrysdi (risdiplam) received a green light from the regulator on August 7 to treat patients aged 2 months and older. The small-molecule drug is a splicing modifier designed to boost full-length motor neuron 2 (SMN2) mRNA expression to increase functional SMN protein production in muscle. In SMA, low levels of SMN protein lead to motor neuron death and muscle atrophy. In trials, Evrysdi improved motor performance and increased survival in patients with SMA. It can be taken orally, which is an important option for patients with this rare and often fatal disease.
Evrysdi sits alongside two other approved SMA treatments: the antisense therapy Spinraza (nusinersen) from Biogen and Ionis Pharmaceuticals, which also targets SMN2 pre-mRNA, and Novartis’s SMN1 gene therapy Zolgensma (onasemnogene abeparvovec). Evrysdi is an orally administered liquid, which gives patients the option of taking the daily dose at home, unlike Spinraza, which must be injected three times a year into the spine, and Zolgensma, a one-shot intravenous infusion (albeit one with only around 5 years of data available). At $2.1 million, Zolgensma is also the world’s most expensive drug, and Spinraza costs $750,000 for the first year and $375,000 every subsequent year. Evrysdi’s lower price — a maximum of $340,000 per year, scaled according to body weight — might afford it a competitive advantage. In addition, oral dosing achieves systemic exposure, which targets tissues and organs outside the central nervous system, so Evrysdi could potentially have a greater disease-modifying effect than Spinraza (although such benefit has yet to be proven clinically). Both Evrysdi and Spinraza can be used to treat children of all ages and adults, but Zolgensma only to treat children younger than two. Although Evrysdi is likely to be a serious competitor to Spinraza, not so the gene therapy Zolgensma, which will probably remain the treatment of choice for children under two years of age.
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