Tofersen

Tofersen, sold under the brand name Qalsody, is a medication used for the treatment of amyotrophic lateral sclerosis (ALS). Tofersen is an antisense oligonucleotide that targets the production of superoxide dismutase 1, an enzyme whose mutant form is commonly associated with ALS. It is administered as an intrathecal injection.

The most common side effects include fatigue, arthralgia (joint pain), increased cerebrospinal (brain and spinal cord) fluid white blood cells, and myalgia (muscle pain).

Tofersen was approved for medical use in the United States in April 2023, and in the European Union in February 2024. The US Food and Drug Administration (FDA) considers it to be a first-in-class medication.

Medical uses
Tofersen is indicated to treat people with amyotrophic lateral sclerosis (ALS) associated with a mutation in the superoxide dismutase 1 (SOD1) gene (SOD1-ALS).

History
Tofersen was developed by Ionis Pharmaceuticals and was licensed to, and co-developed by, Biogen.

The effectiveness of tofersen was evaluated in a 28-week, randomized, double-blind, placebo-controlled clinical study in 147 participants with weakness attributable to amyotrophic lateral sclerosis and a superoxide dismutase 1 (SOD-1) mutation confirmed by a central laboratory. The study randomly assigned 108 participants in a 2:1 ratio to receive treatment with either tofersen 100 mg (n = 72) or placebo (n = 36) for 24 weeks (three loading doses followed by five maintenance doses). The participants were approximately 43% female; 57% male; 64% White; and 8% Asian. The average age was 49.8 years (range from 23 to 78 years).

The stage III clinical trial was conducted by the Neuroscience Institute and Sheffield Institute for Translational Neuroscience (SITraN), both at the University of Sheffield.

The US Food and Drug Administration (FDA) granted the application for tofersen priority review, orphan drug, and fast track designations.

Economics
Only around 1-2% of ALS cases diagnosed in the United States each year carry the specific SOD1 mutation targeted by the drug. Fewer than 500 patients a year are expected to be eligible for the drug, which is expected to cost over $100,000 for a year's treatment.

Legal status
In February 2024, the Committee for Medicinal Products for Human Use of the European Medicines Agency adopted a positive opinion, recommending the granting of a marketing authorization under exceptional circumstances for the medicinal product Qalsody, intended for the treatment of a type of amyotrophic lateral sclerosis caused by a defective superoxide dismutase 1 (SOD1) protein. The applicant for this medicinal product is Biogen Netherlands B.V. The marketing authorisation in the EU was granted on 29 May 2024.