The FDA estimates that there are about five hundred people in the USA with the SOD1 mutation out of a total of approximately thirty thousand ALS patients. According to a recent article in BioPharmaDive, the FDA generally approves a drug based on the drug’s ability to improve a patient’s quality of life or extend the patient’s life. This is an entirely new scenario.
A Small Step with Huge Potential
SOD1, a protein that if mutated can lead to ALS, is blocked by tofersen. The FDA’s (conditional) decision has the potential to affect the way in which other ALS treatments are reviewed and tested.
Tofersen will be sold as Qalsody, and does not fit the usual FDA mold. The drug initially failed to slow the decline of ALS. Biogen’s faith in tofersen, and encouragement from the FDA, prompted multiple meetings with the Agency. The FDA cautioned Biogen that obtaining full approval after a failed clinical trial would be a challenge.
Changing Direction
The second time around, tofersen was judged on its ability to achieve lower levels of neurofilament light chain. It is this characteristic that has drawn a considerable amount of interest. Tofersen is the first ALS drug that has been approved based on biomarker (biological marker) data. A biomarker identifies activity in an organism or cell at a specific date and time.
Biogen has partnered with Ionis Pharmaceuticals in developing tofersen, an antisense therapy. Antisense drugs have the ability to halt the assembly of ineffective proteins.
The study that gave rise to tofersen’s approval showed that levels decreased by 55 % in patients treated with tofersen and a 12% increase when treated with a placebo. All patients in the main study’s extension trial received tofersen resulting in similar changes. Biogen believes there is sufficient evidence to show that tofersen successfully blocks the SOD1 gene thereby benefiting nerve cells.
It is usually a sign of nerve damage when a neurofilament light chain has been discovered in the fluid surrounding the spinal cord and brain. This is especially true with ALS patients.
Then in the spring of 2022, Biogen made the decision to pursue accelerated approval using its neurofilament data. The FDA agreed to review Biogen’s new application.
Mixed Data vs. Urgent Need
The FDA was now in the position of weighing the mixed data against the number of patients who face death within five years after their diagnosis.
The Agency has received criticism from patient advocates who feel that it is not working hard enough to facilitate more ALS treatments for patients.
These factors prompted the FDA to convene a group of outside advisers to consider the positive and negative aspects of tofersen. Although some on the committee hesitated to support tofersen as an effective ALS treatment, they were all in agreement that the drug would be somewhat likely to produce a clinical benefit on a neurofilament light chain.
During part of the Agency’s meeting that was open to the public, several families spoke about the relatives they have lost to SOD1 ALS. One family lost thirty-three relatives across seven generations and another lost twenty-two family members again across several generations.
The advocacy groups claimed that the FDA has already awarded accelerated approval to drugs with mixed track records for various nervous system disorders, namely Biogen’s Aduhelm, approved for Alzheimer’s.
About Cost
Biogen intends to price tofersen in the range of other comparable drugs such as Relyvrio to treat ALS. The drug was approved in 2022 for approximately $158,000 a year. An oral and older version, Radicava, was approved at a cost of $170,000 per year.
The comparison ends there as tofersen is being developed to treat a small number of ALS patients who have been diagnosed with mutations in the SOD1 gene. Therefore, it is not expected to rank as one of Biogen’s featured products. The Stifel analysts see tofersen, at best, generating about $150 million in annual sales.
As far as the out-of-pocket expenses for most eligible patients, Biogen expects it to be less than $50.00 per month.
Please note that this article has been updated with comments from Biogen regarding the price of Qalsody.
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