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General Information
Qalsody (tofersen) is an antisense oligonucleotide (ASO) designed to bind to SOD1 mRNA to reduce SOD1 protein production.
Qalsody is specifically indicated for the treatment of amyotrophic lateral sclerosis (ALS) in adults who have a mutation in the superoxide dismutase 1 (SOD1) gene. This indication is approved under accelerated approval based on reduction in plasma neurofilament light (Nfl) chain observed in patients treated with Qalsody. Continued approval for this indication may be contingent upon verification of clinical benefit in confirmatory trial.
Qalsody is supplied as an injection for intrathecal use.
Recommended Dosage
- Administer Qalsody intrathecally using a lumbar puncture by, or under the direction of, healthcare professionals experienced in performing lumbar punctures.
- The recommended dosage is 100 mg (15 mL) of Qalsody per administration. Initiate Qalsody treatment with three (3) loading doses administered at 14-day intervals. Administer a maintenance dose every 28 days thereafter.
Missed Dose
- If the second loading dose is missed, administer Qalsody as soon as possible, and administer the third loading dose 14 days later.
- If the third loading dose or a maintenance dose is missed, administer Qalsody as soon as possible, and administer the next dose 28 days later.
Mechanism of Action
Qalsody (tofersen) is an antisense oligonucleotide (ASO) designed to bind to SOD1 mRNA to reduce SOD1 protein production. Tofersen causes degradation of SOD1 mRNA through binding to SOD1 mRNA, which results in a reduction of SOD1 protein synthesis.
Side Effects
Adverse effects associated with the use of Qalsody may include, but are not limited to, the following:
- pain
- fatigue
- arthralgia
- cerebrospinal fluid white blood cell increased
- myalgia
Clinical Trial Results
The FDA's accelerated approval was based on the following data. Continued approval for this indication may be contingent upon verification of clinical benefit the ongoing Phase 3 ATLAS study of tofersen in people with presymptomatic SOD1-ALS, which will serve as the confirmatory study.
Efficacy was based on VALOR, a 28-week randomized, double-blind, placebo-controlled clinical study in patients 23 to 78 years of age with weakness attributable to ALS and a SOD1 mutation confirmed by a central laboratory. 108 patients were randomized 2:1 to receive treatment with either Qalsody 100 mg (n=72) or placebo (n=36) for 24 weeks (3 loading doses followed by 5 maintenance doses). Concomitant riluzole and/or edaravone use was permitted for patients and at baseline 62% of patients were taking riluzone, and 8% of patients were taking edaravone.
Over 28 weeks in VALOR, participants in the primary analysis population (n=60) treated with Qalsody experienced less decline from baseline as measured by the Revised Amyotrophic Lateral Sclerosis Functional Rating Scale (ALSFRS-R) compared to placebo, though the results were not statistically significant. In the overall intent-to-treat population (n=108), Qalsody -treated participants experienced a 55% reduction in plasma NfL compared to a 12% increase in placebo-treated participants. Additionally, levels of CSF SOD1 protein, an indirect measure of target engagement, were reduced by 35% in the Qalsody -treated group compared to 2% in the corresponding placebo group.
Approval Date: 2023-04-01
Company Name: Biogen