Biogen’s SMA Drug, Spinraza Continues to Show Benefits in Pre-Symptomatic Patients

By T. Chakraborty, Ph.D.

The Boston-based company announced that its antisense oligonucleotide drug continues to demonstrate benefit in Phase 2, NURTURE trial, the longest study of pre-symptomatic patients with spinal muscular atrophy (SMA).

Spinal muscular atrophy (SMA) is a rare genetic disease characterized by neuromuscular degeneration and weakness that generally leads to paralysis and death. It is an autosomal recessive disorder caused due to defects in both copies of the survival motor neuron 1 (SMN1) gene. The SMN protein is necessary for normal motor functions in the spinal cord. The disease manifestation generally occurs in early life and is the leading cause of death in infants. Roughly 25,000 children suffer from this disease in the USA. Most Type I SMA patients do not survive for more than two years.

Spinraza, an Antisense Oligonucleotide (ASO)

Although the SMN1 gene is defective, SMA patients still have normal copies of the SMN2 gene that performs the same function. Unfortunately, SMN2 produces a low amount of functional protein due to a splicing error, which leads to exon skipping. Researchers at the University of Massachusetts Medical School identified a regulatory sequence in the intronic region, named intronic splicing silencer-N1 (ISS-N1), which promotes the exon skipping in the SMN2 gene. Inhibition of this ISS-N1 region may lead to the production of full-length SMN protein, which can help patients with SMA.

On June 10th, 2020, Biogen announced new updates from the clinical trial NURTURE for their antisense oligonucleotide (ASO) drug, Spinraza (nusinersen), the first FDA approved treatment for SMA. This drug is based on an antisense oligonucleotide approach targeting the ISS-N1 region, thereby increasing the production of full-length SMN protein. Spinraza is injected into the fluid around the spinal cord, where motor neurons reside to deliver the treatment where this disease starts. Originally developed by Ionis Pharmaceuticals, Biogen now holds the global rights to develop, manufacture, and commercialize the drug.

More than 300 patients with SMA across various population groups have received Spinraza and have shown favorable benefits. Two randomized double-blinded trials in infantile (ENDEAR) and late-onset SMA (CHERISH) showed impressive clinical data and encouraged an open-label trial in pre-symptomatic infants (NURTURE). Two other open-label clinical trials are also underway; CS2/CS12 and SHINE.

Update from NURTURE Trial

NURTURE is a Phase 2 open-label clinical trial with 25 pre-symptomatic genetically diagnosed infants. The infants received the drug before 6 weeks of age. The trial was extended for three years to study the long term safety and efficacy of Spinraza. New updates show that after a one year follow up as of February 2020, all patients remained free of permanent ventilation, and the average median age reached 3.8 years old. 92% of the infants continued to walk with assistance.

In the last 11 months, one patient developed the ability to walk with assistance. Around 84% of the patients reached a maximum score on the Children’s Hospital of Pennsylvania Infant Test of Neuromuscular Disorders (CHOP-INTEND) scale. Spinraza did not show any other safety issues. Some adverse events observed were respiratory infection, fever, constipation, headache, vomiting, and back pain.

Dr. Katherine B. Sims, Endowed Chair in Neurogenetics and Director of the Neurogenetics Program, Massachusetts General Hospital, commented, “The impact of early and sustained Spinraza treatment on these infants and their families are remarkable. I’ve had the privilege to watch them grow into active young children, many of whom have experienced progress in motor function consistent with children their age who do not have SMA. The new results from NURTURE continue to bolster the substantial benefit of both prompt diagnosis and early and longer-term treatment with Spinraza.”

The encouraging data from the ongoing and completed trials with Spinraza is encouraging for thousands of kids and their parents who are suffering from this deathly genetic disorder.

Competition from other ASOs

Since its FDA approval in 2016, Spinraza has grown to be Biogen’s biggest revenue generator. Amid the slump caused by direct competition from Novartis’ Zolgensma since last year, Spinraza continues to propel sales. In the first quarter of 2020, Biogen announced US$ 565 million worth earnings for the drug, which is a 9% increase in revenue as compared to the same period in 2019. With Roche’s ASO, risdiplam also knocking the doors for regulatory approval, the SMA market is gearing up for a three-way rivalry.

Editor: Rajaneesh K. Gopinath, Ph.D.

Related Article: FDA Okays Expensive Gene Therapy for Infantile-Onset Spinal Muscular Atrophy

References

1. https://smafoundation.org/about-sma/
2. https://pubmed.ncbi.nlm.nih.gov/29916015/
3. http://investors.biogen.com/news-releases/news-release-details/new-results-landmark-nurture-study-show-pre-symptomatic-sma
4. https://investors.biogen.com/static-files/60eda571-f103-42ee-8b03-5c64571dfc13

Author

Tulip Chakraborty