Emerging Drugs
Emerging Drugs


(Biogen in partnership with Ionis Pharmaceuticals)

Current Status

Researchers have completed a phase 3 clinical trial (VALOR) for people with ALS with SOD1 mutations. The initial readout of results was presented on October 17 at the 2021 American Neurological Association (ANA) virtual meeting. Read Biogen's news release here and statement here. The ALS Association released this statement in response.


What does tofersen do?

Tofersen is designed to slow the progression of ALS and potentially prevent the disease from developing in people with SOD1 mutations.

What is a SOD1 mutation?

Mutations in the SOD1 gene appear in about 12-20 percent of people with familial ALS and 1-2 percent of people with sporadic (or singleton) ALS. The SOD1 gene directs the production of a protein that is also called SOD1. This protein normally helps clear out toxins from the brain, but when the SOD1 gene harbors certain mutations, it creates a defective SOD1 protein. The malformed protein not only fails to do its normal job, but it also creates its own problems. In people with SOD1 mutations, the SOD1 protein clumps together with other copies of itself and these clumps damage the nervous system, leading to the symptoms of ALS.

How does tofersen work?

Tofersen works by blocking the production of the SOD1 protein using a molecule called an antisense oligonucleotide. An antisense oligonucleotide is a small string of synthetic DNA that, in this case, prevents the SOD1 protein from getting made.


What have researchers learned about tofersen so far?

A phase 1/2 clinical trial showed us that the treatment was safe and lowered SOD1 levels in the cerebral spinal fluid in a group of 50 people, and that it may slow the progression of ALS. Researchers tested a larger group of 183 people in a phase 3 trial to confirm whether the therapy slows ALS down. This trial recently finished, and the results have not been released yet.

How is tofersen administered?

Tofersen is administered through a lumbar puncture. A doctor inserts a thin needle into the space around the spinal cord in the lower back and injects the drug. The final dosing regimen has not been released by Biogen.

How  is The ALS Association is supporting the development of tofersen?

The ALS Association was the first to invest in antisense technology targeting the second most common genetic cause of ALS - SOD1. We supported antisense research despite the high risk of the technology not coming to fruition. Our initial investment of $1.5 million to ALS researchers propelled the concept all the way from an academic laboratory in partnership with industry to testing the approach in the clinic.

Our approach to research, which focuses on translating concepts into therapies, facilitated the development of potential antisense treatments not only for ALS, but also for other neurodegenerative diseases, including Huntington’s disease, Alzheimer’s disease frontotemporal dementia and others. In this way, the value of our initial investment has ballooned from $1.5 million to more than $100 million.

The Association has also provided close to $1M of direct funding to three different projects including late-stage preclinical study and early clinical phase 1 trial. Furthermore, we provided complementary funding to NEALS for trial infrastructure for tofersen’s early clinical phase 1 trial.

In December 2016, the FDA approved an antisense drug, Spinraza, targeting spinal muscular atrophy, a common neuromuscular disease and the leading genetic cause of death in infants and toddlers. This is the first approved treatment for this fatal disorder. This success gives us much hope for the future of antisense therapies targeting ALS.

How can people with ALS access tofersen?

Biogen has expanded eligibility for its ongoing early access program (EAP) to all people with SOD1-ALS, in countries where such programs are permitted by local regulations and future access may be secured. Learn more here.

Learn more about tofersen

Biogen’s website here.

Read past ALS Association blogs featuring tofersen here:

Learn more about the recently completed Phase 3 clinical trial on the Northeast Amyotrophic Lateral Sclerosis Consortium (NEALS) page.

Learn more from the International Alliance of ALS/MND Associations.

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Emerging Drugs