Risdiplam (Evrysdi) is a modifier of SMN2 (survival of motor neuron 2) protein that has got FDA approval on 8th August 2020. Spinal muscular atrophy is a hereditary disorder with mutations in the chromosome 5q. It is an autosomal recessive disorder affecting 4 - 10 per 100,000 live births.
Depending on the age and severity of the disease, it is classified into five different types as:
| Type | 0 | 1 | 2 | 3 | 4 |
| Age of Onset | Prenatal | < 6 months | 6 – 18 months | > 18 months | >5 years |
| Requires Respiratory support at birth | Yes | No | No | No | No |
| Can Sit | No | No | Yes | Yes | Yes |
| Can Stand | No | No | No | Yes | Yes |
| Can Walk | No | No | No | Assisted | Yes |
| Life expectancy | Less than 6 months | Less than 2 years | 10 – 40 years | Adult | Adult |
| Number of SMN2 Copy number | 1 | 2 | 3 | 3 - 4 | >4 |
Clinical Classification of Spinal Muscular Atrophy Spinal muscular atrophy is characterized by progressive degeneration of the nerve cells in the anterior horn. It does not affect the brain and hence cognition and intellect are preserved.
Most patients develop progressive symmetrical weakness of the lower limbs with hypotonia. Sensations are intact since there is sparing of the posterior horn cells and the reflexes are absent in the affected areas.
Weakness is greater in the lower limbs and the proximal muscles than in the upper limbs. The disease is diagnosed in patients with classical history, muscle biopsy, and electromyography. However, the disease is confirmed and classified with genetic sequencing studies. More than 94% of the patients have a homozygous deletion of exon 7.
Treatment of spinal muscular atrophy:
No effective treatments were available prior to Risdiplam FDA approval. Treatment to date was supportive and included nutritional support, respiratory support, and orthopedic intervention such as the use of spinal bracings.
Few available disease-modifying drugs that are used include:
- Nusinersen
- Onasemnogene Abeparvovec
Both treatments are extremely expensive and used in experimental models. Onasemnogene Abeparvovec is a one-time infusion of the normal gene, replacing the abnormal one, while Nusinersen is administered intrathecally. Prognosis is guarded and depends on the type of spinal muscular atrophy. Only patients with type 4 SMA survive until adult life.
Risdiplam (Evrysdi) FDA Approved:
Risdiplam (Evrysdi) is the only orally available drug that got recent FDA approval. It has a unique mechanism of action that modifies the SMN2 (survival of motor neuron 2) protein. It is available as a dry powder that is reconstituted at 0.75 mg/ml concentration. However, it is available for use only in children who are 2 months of age or older. Billy Dunn, M.D., director of the Office of Neuroscience in the FDA’s Center for Drug Evaluation and Research rightly stated [Ref]:
“Evrysdi is the first drug for this disease that can be taken orally, providing an important treatment option for patients with SMA, following the approval of the first treatment for this devastating disease less than four years ago,"
The drug has favorable side effects and superior efficacy. In clinical trials, 57% of the patients noticed stabilization of their motor functions and 49% of the patients did not require hospitalizations.
The drug is going to cost a maximum of $340,000 per year and may be available within the upcoming two weeks. Read Risdiplam (Evrysdi) Drug Details here: Risdiplam (Evrysdi): Indications, Dose, Side effects, MOA.
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