FDA approves high-dose Spinraza regimen for new, existing SMA patients
US nod for new treatment option met with enthusiasm by community, advocates
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- The FDA has approved a high-dose Spinraza regimen for people with SMA, soon to be available to both current and new therapy users in the U.S.
- This regimen features a shorter loading phase and higher maintenance doses.
- The high-dose regimen demonstrated improved motor function and survival outcomes in clinical testing, with a safety profile consistent with lower doses.
The U.S. Food and Drug Administration (FDA) has approved a high-dose regimen of Spinraza (nusinersen) — one that allows patients to receive consistently higher doses of the therapy after a shorter initial treatment loading phase — for spinal muscular atrophy (SMA).
The new dosing regimen is authorized for use by both SMA patients new to the therapy and those already on Spinraza.
“With more than 10 years of clinical data on SPINRAZA, the development of the High Dose Regimen reflects … our unwavering commitment to the SMA community to optimize treatment options. We are grateful to the community for their support and contributions toward this milestone,” Priya Singhal, MD, executive vice president and head of development at Biogen, Spinraza’s developer, said in a company press release.
The FDA approval of the high-dose regimen comes on the heels of similar decisions in the European Union, Switzerland, and Japan. Biogen said it is now actively working with other regulators across the globe to bring in this additional dosing option to SMA patients in other parts of the world.
According to Biogen, the newly-approved high-dose regimen should become available in the U.S. in the coming weeks.
The approval of this new dosing regimen was met with enthusiasm by the SMA community.
“Nearly [10] years ago, the approval of Spinraza marked a turning point in SMA care and changed what the community believed was possible, with Biogen becoming a trusted partner for thousands of people living with SMA,” said Kenneth Hobby, president of Cure SMA, a U.S.-based nonprofit.
“Today’s approval of High Dose Spinraza makes progress in addressing unmet needs of the SMA community,” Hobby said.
Safety of high-dose Spinraza consistent with original regimen
A genetic disorder, SMA is mainly caused by mutations that lead to low levels of the survival motor neuron protein, known as SMN. The lack of this protein causes motor neurons — the nerve cells that control movement — to sicken and die.
Spinraza works to boost SMN protein production, thereby helping to preserve motor neuron health. It was the first treatment proven to slow SMA progression approved by the FDA. The therapy is administered by an injection into the spinal canal, also known as an intrathecal injection.
Under its original FDA approval a decade ago, the therapy was given at a recommended dose of 12 mg. The originally-approved dosing regimen required four loading doses — three given every other week, then a fourth one month later — followed by maintenance dosing every four months.
As stated in Spinraza’s prescribing information, the now-approved high-dose regimen comprises two loading doses of 50 mg given two weeks apart, followed by maintenance doses of 28 mg given every four months.
Patients who had been on the original regimen can switch to the high-dose treatment by receiving a single 50 mg loading dose at least four months after their last 12 mg maintenance dose. After that, these individuals can start receiving 28 mg maintenance doses every four months.
Optimizing the dose of [Spinraza] builds on a therapy that we already know can change lives. The high dose regimen demonstrated meaningful clinical benefit while maintaining a well characterized safety profile.
Biogen’s application seeking the approval of the high-dose regimen was based on data from the Phase 2/3 DEVOTE clinical trial (NCT04089566). Results from that trial showed that previously untreated children with SMA given the high-dose regimen had better motor function and survival outcomes than patients given a placebo in a prior Phase 3 clinical trial of Spinraza, known as ENDEAR (NCT02193074).
Data from DEVOTE and an extension study called ONWARD (NCT04729907) indicated that SMA patients who switched from the original regimen to the high-dose regimen generally had stable or improved motor function.
The safety profile of the high-dose regimen of Spinraza in DEVOTE was consistent with the therapy’s known safety profile when used at lower doses. The most common side effects seen in people treated with the high-dose regimen included pneumonia, COVID-19, pneumonia aspiration, and malnutrition in those with infantile-onset SMA.
“Optimizing the dose of [Spinraza] builds on a therapy that we already know can change lives. The high dose regimen demonstrated meaningful clinical benefit while maintaining a well characterized safety profile,” said Richard Finkel, MD, director of the Center for Experimental Neurotherapeutics at St. Jude Children’s Research Hospital. “I believe High Dose Spinraza will play an important role in the future of SMA care.”
