Tofersen (Qalsody) has been granted accelerated approval by the FDA to treat amyotrophic lateral sclerosis (ALS) patients with SOD1 gene mutations. This marks the first time an ALS drug has been approved under the accelerated approval pathway, and the second ALS drug approved in under 12 months. Tofersen is an antisense oligonucleotide that targets SOD1 mRNA to reduce SOD1 protein synthesis.
Clinical Trial Results
The VALOR clinical trial evaluated Tofersen’s effectiveness over 28 weeks. Although the drug did not meet its primary endpoint of improving motor control or muscle strength compared with a placebo, it did lower SOD1 protein in cerebrospinal fluid and reduce plasma neurofilament light (NfL). Data from the open-label extension suggested that long-term use of Tofersen could have clinical benefits.
Risks and Side Effects
The most common side effects observed in Tofersen trials were pain, fatigue, arthralgia, increased CSF white blood cells, and myalgia. The FDA has noted that additional risks are described in the drug’s prescribing information. Tofersen is administered intrathecally at a recommended dosage of 100 mg per administration, with patients receiving three initial doses administered at 14-day intervals followed by a maintenance dose every 28 days.
Tofersen’s effectiveness was evaluated in the 28-week phase III VALOR clinical trial. The drug did not meet its primary endpoint of improving motor control or muscle strength compared with placebo, but it did reduce SOD1 protein in cerebrospinal fluid (CSF) and lowered plasma NfL. Data from the open-label extension suggested long-term use of tofersen may have clinical benefit.”We see clear evidence that the drug slows down the initiating factor — a SOD1 mutation — as well as the neurodegenerative disease process,” said investigator Timothy Miller, MD, PhD, of Washington University in St. Louis, when VALOR trial results were published.”We didn’t see substantial clinical improvement at 6 months, but the stabilization in function and strength at longer time points suggests it may take time for people to heal from the damage that has already been caused,” Miller observed.
Tofersen, an antisense oligonucleotide, has been granted accelerated approval by the FDA to treat amyotrophic lateral sclerosis (ALS) patients with SOD1 gene mutations. The drug targets SOD1 mRNA to reduce SOD1 protein synthesis. Tofersen is the first ALS drug approved under the accelerated approval pathway and the second ALS drug approved in under 12 months. The VALOR clinical trial evaluated Tofersen’s effectiveness over 28 weeks. Although the drug did not meet its primary endpoint of improving motor control or muscle strength compared with a placebo, it did lower SOD1 protein in cerebrospinal fluid and reduce plasma neurofilament light (NfL). Data from the open-label extension suggested that long-term use of Tofersen could have clinical benefits. The most common side effects observed in Tofersen trials were pain, fatigue, arthralgia, increased CSF white blood cells, and myalgia. The FDA has noted that additional risks are described in the drug’s prescribing information. Tofersen is administered intrathecally at a recommended dosage of 100 mg per administration, with patients receiving three initial doses administered at 14-day intervals followed by a maintenance dose every 28 days.
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