Would you be shocked to find out that before Evrysdi, there were zero orally-administered drugs approved to treat patients with spinal muscular atrophy (SMA)? But now, things have changed. Last week, the FDA announced its approval for Evrysdi (risdiplam) for patients aged 2 months or older. This marks the first ever orally-administered therapy for SMA.
Spinal Muscular Atrophy (SMA)
Affecting around 1 in 10,000 people, spinal muscular atrophy (SMA) is a rare genetic disorder caused by SMN1 gene mutations. This mutation causes a death or loss of motor neurons. As a result, patients experience muscle weakness and degeneration. Ultimately, this contributes to movement difficulties, such as poor breathing, swallowing, walking, and sitting.
There are four main types of SMA. The type I, also known as Werdnig-Hoffman disease, is fairly severe. It is usually diagnosed at or quickly following birth. Symptoms include developmental delays, breathing and swallowing issues, and an inability to sit or support the head without assistance. Next, type II SMA affects children between 6-12 months. These patients cannot sit or walk independently.
In patients with type III, or Kugelberg-Welander syndrome, symptom onset occurs between childhood and early adolescence. Patients may experience difficulty walking or climbing stairs, which grows progressively worse. Finally, in type IV, symptom onset does not occur until after age 30. Patients with this condition experience tremors or twitching, muscle weakness, and difficulty breathing. Learn more about SMA here.
Evrysdi
Developed by Genentech, Evrysdi increases the production of survival of motor neuron (SMN) proteins. Since SMA-related gene mutations cause a loss of motor neurons, Evrysdi is uniquely poised to address this deficiency. Researchers tested the safety, tolerability, and efficacy of the treatment in two clinical trials.
The first trial, which examined 21 patients with infantile-onset SMA, monitored whether Evrysdi helped patients sit up and breathe without support. Within 1 year of treatment, 41% (9 patients) could sit without support for over 5 seconds. Within 2 years of treatment, 81% (17 patients) were surviving without additional ventilation or breathing support.
In the second trial, for patients with late-onset SMA, 180 patients between the ages of 2 and 25 received either Evrysdi or a placebo. Researchers wanted to determine how their motor function changed or improved following treatment. On average, patients taking the placebo experienced a 0.19 MFM32 score decrease. Alternately, those using Evrysdi experienced an average 1.36 MFM32 score increase within one year.
Although the medication is safe and fairly well-tolerated, there were some adverse reactions, which included:
- Fever
- Rash
- Mouth ulcers
- Joint pain
- Urinary tract and upper respiratory infections
- Constipation or diarrhea
- Vomiting
- Pneumonia
In addition to its approval, Evrysdi was also given Orphan Drug and Fast Track designations, Priority Review, and a Rare Pediatric Disease Priority Review Voucher.
