Tofersen Did Not Improve Function in Genetic Amyotrophic Lateral Sclerosis But May Reduce Aspects of Disease Progression

In the phase 3 VALOR study (NCT02623699), people with superoxide dismutase type-1 ALS (SOD1-ALS) treated with tofersen (BIIB067; Biogen, Cambridge, MA) did not  have statistically significant improvement on the Revised Amyotrophic Lateral Sclerosis Functional Rating Scale (ALSFRS-R) compared with placebo. Data suggest reduced disease progression (eg, improved motor function, respiratory function, and quality of life) may have occurred based on multiple secondary and exploratory endpoints. 

Cerebrospinal fluid (CSF) levels of SOD1 protein were 38% and 26% higher with tofersen vs placebo in the faster- and slower-progressing populations respectively. Neurofilament light chain (NfL) in the same groups of 67% and 48% in the faster- and slower-progressing populations respectively.

“The results from the VALOR study are encouraging as they show reduction of SOD1 protein, reduction of neurofilament, a potential biomarker for neurodegenerative disease, and positive signals across multiple key endpoints including measures of important aspects of the daily lives of SOD1-ALS patients,” said Timothy Miller, MD, PhD, principal investigator of VALOR and ALS Center director at Washington University School of Medicine, St. Louis. “The wait for new options has been long and difficult for the ALS community, and we welcome this important research advancement in this difficult to treat disease space.” 

VALOR was a 28-week phase 3 randomized double-blind placebo-controlled study of tofersen 100 mg in adults with ALS associated with a SOD1 mutation. In total, 108 participants were randomly assigned 2:1 to receive 100 mg tofersen or placebo. In the study, 60% of participants met the study’s protocol-defined enrichment criteria for rapid disease progression, comprising the primary analysis population. The results showed 48% participants did not meet these prognostic enrichment criteria.

The most common adverse events in participants receiving tofersen were procedural pain, headache, pain in extremity, fall and back pain.