Tofersen

QALSODY is 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 chain (NfL) observed in patients treated with QALSODY. Continued approval for this indication may be contingent upon verification of clinical benefit in confirmatory trial(s). QALSODY is an antisense oligonucleotide 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 chain observed in patients treated with QALSODY.

12.1. Mechanism of Action Tofersen is an antisense oligonucleotide that causes degradation of SOD1 mRNA through binding to SOD1 mRNA, which results in a reduction of SOD1 protein synthesis.

QALSODY is administered intrathecally. Dosing Information. Recommended dose: 100 milligrams (15 mL) per administration Initiate QALSODY treatment with 3 loading doses administered at 14day intervals. A maintenance dose should be administered once every 28 days thereafter. Preparation and Administration Instructions. Allow to warm to room temperature prior to administration Administer within 4 hours of removal from vial Prior to administration, remove approximately 10 mL of cerebrospinal fluid Administer as an intrathecal bolus injection over 1 to 3 minutes 2.1. Dosing Information 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.

None. None

Myelitis and/ or Radiculitis: Serious events of myelitis and radiculitis have been reported. Monitor for symptoms, diagnostic workup and treatment should be initiated according to the standard of care. Papilledema and Elevated Intracranial Pressure: Serious events of papilledema and elevated intracranial pressure have been reported. Monitor for symptoms, diagnostic workup and treatment should be initiated according to standard of care. Aseptic Meningitis: Serious events of aseptic meningitis have been reported. Monitor for symptoms, diagnostic workup and treatment should be initiated according to standard of care. 5.1. Myelitis and/or Radiculitis Serious adverse reactions of myelitis and radiculitis have been reported in patients treated with QALSODY. Eight patients treated with QALSODY experienced myelitis or radiculitis in the clinical studies.

The following clinically significant adverse reactions are discussed elsewhere in the labeling: Myelitis and/or Radiculitis Papilledema and Elevated Intracranial Pressure Aseptic Meningitis The most common adverse reactions (≥ 10% of patients treated with QALSODY and greater than placebo) were pain, fatigue, arthralgia, cerebrospinal fluid white blood cell increased, and myalgia. (Section 6.1 ) 6.1. Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of QALSODY cannot be directly compared to rates in clinical trials of other drugs and may not reflect the rates observed in practice. The safety of QALSODY 100 mg was evaluated in 147 patients with SOD1-ALS. The median patient exposure was 199.7 weeks (range from 4 to 321 weeks).

Store refrigerated between 2°C to 8°C (36°F to 46°F) in the original carton to protect from light. Do not freeze. If no refrigeration is available, QALSODY may be stored in its original carton, protected from light at or below 30°C (86°F) for up to 14 days. If removed from the original carton, unopened vials of QALSODY can be removed from and returned to the refrigerator, if necessary, for not more than 6 hours per day at or below 30°C (86°F) for a maximum of 6 days (36 hours).