Report Outlines Optimal Approaches to Address Nusinersen Treatment Gaps

Researchers outlined recommended treatment plans to build back effective levels of nusinersen following treatment gaps.

For patients receiving nusinersen for their spinal muscular atrophy (SMA), situations like the ongoing COVID-19 pandemic or pregnancy can lead to missing a maintenance dose(s) of the treatment, prompting questions on how to best resume treatment. In a recent paper, researchers reviewed the available literature to determine the best path for restarting treatment to ensure optimal efficacy.

Based on data from 10 different studies, they outlined recommended treatment plans to build back effective levels of nusinersen based on the gap's duration, beginning at 8 months. The plans should not introduce any new safety concerns.

Typically, nusinersen is initially administered as 3 doses at 14-day intervals followed by a fourth dose 30 days later, prior to maintenance doses administered every 4 months.

“A longer treatment interruption may occur in the context of clinical practice for a number of reasons, such as the ongoing COVID-19 pandemic, pregnancy/childbirth, or changing therapy and subsequently returning to nusinersen,” wrote the researchers. “This analysis is based on a population pharmacokinetic (PK) model, given the limited data from clinical trials on dosing delays. Because of the different potential reasons for treatment interruptions, all dosing intervals are expressed as time since the last dose was administered,” they said.

For patients who missed treatment for at least 8 months but less than 16 months, the data support 2 doses of nusinersen 14 days apart before the maintenance dose of injections every 4 months. In one example from the model, the researchers found that following this treatment plan, steady-state nusinersen concentrations would restore approximately 19.5 months quicker than if maintenance dosing was resumed without first administering the 2 doses at 14-day intervals.

For patients who missed treatment for at least 16 months but less than 40 months, the data indicated a need for 3 nusinersen doses, each 14 days apart, before the maintenance injections. Of note, no patient in the collection of studies had a treatment interruption of more than 16 months.

In the case of patients missing treatment for 40 months or longer, the researchers determined that, based on their model, patients would need to receive the full loading dose regimen, consisting of the 4 initial nusinersen doses, before receiving maintenance injections every 4 months.

“The modeled dosing regimens are consistent with the currently approved dosing regimen, in that there should be ≥ 14 days between the first 3 loading doses. If a fourth dose is required, this dose should be administered 30 or 35 days later, consistent with the current label-approved loading regimen,” noted the researchers.

“Although our PK modeling included a fourth dose 30 days after the third dose, our results are similar and also apply to a fourth dose being administered 35 days after the third dose; thus, they are applicable to different regions, which have some differences in this interval as per approved labels,” they continued. Authors added that they do not expect any new safety issues in patients resuming treatment under the dosing regimens outlined.

According to the researchers, following these proposed treatment plans will allow for “rapid” restoration of nusinersen levels in the cerebral spinal fluid that are comparable to those seen in patients with no dose interruptions. They noted that their model did not address cases of repeated dosage interruptions.


MacCannell D, Berger Z, Kirschner J, et al. Restoration of nusinersen levels following treatment interruption in people with spinal muscular atrophy: simulations based on a population pharmacokinetic model. CNS Drugs. Published online January 26, 2022. doi: 10.1007/s40263-022-00899-0

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