TOFERSEN INJ,SOLN

Clinical Criteria Summary

Notably decreased respiratory function and dyspnea (total score of 3 or less points on ALSFRS-R items for dyspnea, orthopnea, or respiratory insufficiency [sum of questions 10, 11 and 12 on the ALSFRS-R])
Bilevel positive airway pressure (BiPAP) dependent (use 24 hours per day)

Care provided by a VA neurologist or locally designated ALS expert
Diagnosis of superoxide dismutase 1 (SOD1) ALS made or confirmed by a VA neurologist or locally designated ALS expert
Laboratory documentation of a pathogenic SOD1 mutation in the electronic medical record
Documentation of an itemized ALSFRS-R score in the electronic medical record

Tofersen has only been studied in patients with forced vital capacity (FVC) of 50% or higher, or FVC of 45 – 50% if the FVC had not declined more than 5% in the last 6 months.

Adults with amyotrophic lateral sclerosis (ALS) who have a mutation in the SOD1 gene
Indicated for SOD1 ALS only; no evidence of effectiveness in other familial types of ALS or sporadic ALS

Intrathecal injection: 100 mg/15 mL solution in a single-dose vial
Dosing regimen: 100 mg intrathecally every 14 days for 3 doses, then starting 28 days after the third dose, 100 mg intrathecally every 28 days
Must be administered by a healthcare professional experienced in lumbar punctures

Myelitis and/or radiculitis: Symptomatic management with or without drug discontinuation may be required if symptoms occur
Papilledema and elevated intracranial pressure (ICP): Requires treatment leading to symptom resolution; discontinuation is not required
Aseptic meningitis: Monitor for serious cases; nonserious elevations of white blood cells in cerebrospinal fluid (CSF) have been reported

Pregnancy: No adequate data to assess risks for birth defects, miscarriage, or developmental/maternal effects
Lactation: No data on presence in breast milk; weigh unknown infant developmental/health risks against maternal clinical need

Accelerated approval is based on reduction of serum neurofilament light chain (NfL) levels as a surrogate marker for slowed neurodegeneration
Impact on specific functional domains and/or survival is unclear due to lack of established correlation between NfL changes and clinical change in ALS
Continued FDA approval is contingent upon verification of clinical benefit in confirmatory trial(s)
Patient/family/caregiver counseling regarding treatment administration implications (e.g., travel to clinic, tolerance of routine lumbar punctures) and realistic expectations for efficacy is imperative