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Here’s Why FDA Committee’s Recommendation on Tofersen Matters to Everyone

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The FDA advisory committee vote on tofersen Wednesday was an exciting and critical moment in the ALS community’s efforts to find new treatments and cures. The committee voted unanimously to recommend accelerated approval of the new treatment.

Most of the time, the FDA follows these recommendations, so we are hopeful tofersen will be approved in late April.

The advisory committee’s decision on tofersen represents a critical moment for everyone living with ALS and their loved ones – and for those who may be diagnosed in the future. Here’s why:

  1. This would be the first use of accelerated approval in ALS.
    Accelerated approval is different than full approval in that treatments approved under the accelerated approval pathway must still show confirmatory evidence of clinical benefit or the FDA can take steps to pull the treatment from the market. But it does allow for treatments to get to people living with ALS faster.
    As we said in our testimony to the advisory committee, given the data at this stage, we believe tofersen meets all three conditions required for accelerated approval: treating a serious condition, providing a meaningful advantage over existing therapies, and demonstrating an effect on a surrogate biomarker (i.e., neurofilament light [NfL]) that is likely to predict clinical benefit. 
  2. This was the first time in ALS that a biomarker was credibly used as a surrogate endpoint.
    This one gets a little technical, but it is important. The accelerated approval pathway allows the FDA to approve drugs quickly based on a surrogate endpoint — in this case, the biomarker neurofilament light (NfL). Neurofilament light levels in the blood and spinal fluid indicate damage that is happening to motor neurons. Tofersen was shown to reduce levels of neurofilament light during the clinical trial. However, clinical benefits did not appear until well after the trial was over and into the open label extension period. The advisory committee found that the neurofilament light levels indicate a change in the course of disease for people receiving the treatment which translates into benefits such as longer life, increased muscle function and reduced disease progression — some months after neurofilament levels go down.
  3. The underlying technology behind tofersen is very promising.
    Antisense technology arises from very long investments made by The ALS Association, the NIH, and the companies IONIS and Biogen, and even more partners studying biomarkers like neurofilament. Tofersen is a direct product of the donations from the ALS community, the strong advocacy work by the ALS community to get more research funding for ALS, the scientists and clinicians carrying out this work, and most importantly, the many people living with ALS who volunteered to participate in this research and their loved ones and caregivers. Your work is making ALS more livable every day.
  4. This is the first gene-based therapy for ALS that appears likely to be approved.
    At least 10% of ALS cases are familial and there are other potential gene-based therapies being studied. While this is the first, we are hoping that gene therapies using antisense and other approaches are developed for treating both familial and sporadic forms of ALS.
  5. Tofersen is being studied to see if it can prevent the onset of ALS altogether.
    Antisense technology may provide the opportunity to prevent ALS. There is an ongoing trial of people with the SOD1 gene to see if tofersen can prevent the onset of ALS in people who have the gene mutations but do not yet have symptoms.
  6. The entire ALS community was united in advocating for tofersen!
    We are grateful to the many people living with ALS and their loved ones and caregivers who gave powerful testimony to the FDA advisory committee Wednesday. And we thank everyone who advocated for approval of tofersen. Your advocacy has had a clear impact in the drug development process, helping expand industry and government interest in developing therapies that specifically target sporadic and genetic forms of ALS.

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