Part 3 trial of tofersen exhibits advantages in treating uncommon type of ALS

September 22, 2022

2 min learn

Miller stories serving as a advisor to Biogen, Bioio, Cytokinetics, Disarm Therapeutics, Ionis and UCB. Please see the examine for all different authors’ related monetary disclosures.

A section 3 trial that evaluated the protection and efficacy of the intrathecally administered antisense oligonucleotide tofersen diminished concentrations of superoxide dismutase 1 protein in sufferers with ALS who had mutations within the gene.

Roughly 2% of ALS instances are related to mutations within the gene encoding superoxide dismutase 1 (SOD1), Timothy M. Miller, MD, PhD, codirector of the ALS Middle at Washington College Faculty of Drugs in St. Louis, and colleagues wrote within the New England Journal of Drugs.

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Miller and colleagues randomly assigned adults with SOD1 ALS in a 2:1 ratio to obtain both eight doses of tofersen (100 mg) or placebo over a interval of 24 weeks.

Major endpoints had been calculated by scores on the ALS Useful Score Scale (ALSFRS) from baseline to week 28. Secondary endpoints included adjustments within the whole focus of SOD1 protein in cerebrospinal fluid, neurofilament gentle chains in plasma and in handheld dynamometry in 16 muscular tissues.

Seventy-two sufferers obtained tofersen (39 predicted to have quicker illness development), and 36 obtained placebo (21 to have quicker development). Within the quicker development subgroup, the change to week 28 in ALSFRS scores was –6.98 within the tofersen group and –8.14 within the placebo group — a distinction of 1.2 factors; 95% CI, –3.2 to five.5).

Moreover, tofersen led to higher reductions in concentrations of SOD1 in cerebrospinal fluid and of neurofilament gentle chains in contrast with placebo.

“I see three key take residence factors from these knowledge. First, tofersen clearly results in decreasing of SOD1 protein, as can be anticipated. Second, there’s substantial decreasing of neurofilament ranges, which I interpret as doubtlessly slowing the underlying illness course of. And, third, there’s a significant scientific profit when wanting on the later time factors within the open label extension,” Miller mentioned in a press launch from Biogen, producer of the drug.

In line with the examine, most typical hostile occasions included procedural ache, headache, ache within the arms or legs, falls and again ache. The incidence of procedural ache and headache was related between the 2 teams, whereas ache within the arm and legs and again ache had been extra frequent in those that obtained tofersen.

Seven whole sufferers had severe neurological hostile occasions, together with myelitis, chemical or aseptic meningitis, lumbar radiculopathy, elevated intracranial stress and papilledema.


The New England Journal of Drugs publishes pivotal tofersen knowledge that present advantages in uncommon, genetic type of ALS. Revealed Sept. 21, 2022. Accessed Sept. 22, 2022.


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