Spinal muscular atrophy (SMA) patients in the European Union will soon have access to Spinraza (nusinersen), the first treatment approved for people with this disease and one able to treat almost all types of SMA.
The European Commission announced late Thursday that it had approved Spinraza, marketed by Biogen, to treat SMA in both children and adults. The decision followed an accelerated review granted to the treatment by the European Medicines Agency, the EU equivalent of the U.S. Food and Drug Administration.
Spinraza was approved by the FDA in December 2016 to treat SMA types 1–3 in children and adults.
“This is a landmark day for the European SMA community. The approval of Spinraza to treat a broad range of patients with SMA provides patients currently living with SMA hope for disease stabilization or improvement,” Eugenio Mercuri, a doctor at Università Cattolica del Sacro Cuore in Rome, said in a press release. “I am encouraged that the approval of Spinraza may demonstrate the potential of other antisense oligonucleotides to treat more neurodegenerative disorders.”
The approval was based largely on positive results seen in two Phase 3 clinical trials, ENDEAR (NCT02193074) and CHERISH (NCT02292537). Both trials were stopped early after Spinraza proved quite effective. Enrolled children were then moved to an ongoing open-label extension study called SHINE (NCT02594124), where all are receiving the treatment.
Data from CHERISH showed a significant improvement in motor skills and muscle function, as measured by a greater than three-point improvement in the Hammersmith Functional Motor Scale-Expanded (HFMSE) after 15 months. The mean improvement increase was four points in treated children, compared with a 1.9-point decrease in those given placebo.
An end-of-study analysis in ENDEAR found some treated children achieving unheard-of motor milestones for SMA, including full head control, and the ability to roll, sit, and stand.
The EC decision was also supported by results from open-label studies in pre-symptomatic and symptomatic children with, or most likely to develop, SMA types 1, 2 or 3.
“The approval of Spinraza by the European Commission is a triumph for our community. Patients and families affected by SMA in Europe may now have a brighter future than before Spinraza was available,” said Joanna Mitchell, CEO of SMA Trust. “We are grateful for the perseverance of the European SMA community as we waited for this day, and for the rigorous clinical work that resulted in a broad label that may offer access to many patients in Europe.“
Spinraza’s availability in particular European countries, as well as its cost, will be determined by the respective governments and health agencies of those countries. Biogen said in the news release that it has been working with various EU health systems and government agencies to help patients secure access.
In the U.S., the therapy has a list price of $125,000 per dose, and the first year of treatment’s out-of-pocket cost is $750,000 for six injections. It is reported to have generated sales of $47 million in the first quarter of 2017.
Spinraza is administered via intrathecal injection, which delivers drugs directly to the cerebrospinal fluid around the spinal cord, where motor neurons degenerate in individuals with SMA due to insufficient levels of survival motor neuron (SMN) protein.
SMA is a hereditary disease that causes weakness and muscle wasting due to the loss of lower motor neurons — specialized nerve cells in the spinal cord and brainstem — that control movement.
Type 1 SMA is the most severe form of the disease, usually diagnosed at birth or within the first six months of life, and is caused by mutations in the SMN1 gene that lead to a shortage of the SMN protein.
The treatment is an antisense oligonucleotide designed to alter splicing of SMN2, a gene nearly identical to SMN1 that in healthy people produces only a small amount of the SMN protein. It aims to enable SMN2 to produce adequate levels of full-length SMN protein to improve motor neuron survival.
Biogen licensed the global rights to develop, manufacture, and commercialize Spinraza from Ionis Pharmaceuticals in August 2016. Based on the EU approval, Ionis earned a $50 million milestone payment from Biogen, with a right to receive tiered royalties on global sales. To date, Ionis has earned more than $375 million from Biogen related to Spinraza.