Written By: Pharmacally Medical News Desk
Biogen reported final Phase 3 VALOR and open-label extension results for QALSODY in Superoxide Dismutase-1 Amyotrophic Lateral Sclerosis (SOD1-ALS), showing long-term outcomes that have now been published in JAMA Neurology. More than 3.5 years of follow-up show that earlier initiation of treatment was associated with a slower decline in motor function, breathing and strength, along with a lower risk of death or permanent ventilation. Reductions in neurofilament, a marker of neurodegeneration, were sustained and support QALSODY’s biological impact in SOD1-ALS.
Stephanie Fradette, Head of the Neuromuscular Development Unit at Biogen says the final VALOR and OLE results suggest that targeting the right biology with the right therapy may change the course of ALS and improve outcomes. She also highlights that reductions in neurofilament are now helping guide earlier research decisions, and credits study participants, caregivers, and clinical teams for making this progress possible.
VALOR Trial
VALOR (NCT02623699) was a six-month, randomized, double-blind, placebo-controlled study enrolling 108 adults with SOD1-ALS. Participants who completed VALOR could enter the open-label extension trial (NCT03070119), and 95 participants did so. Median follow-up reached 4.9 years.
Key highlights included participants who began QALSODY earlier generally had slower functional decline. Early-start treatment was linked to improved strength measures in 27 percent of participants over roughly three years. Faster-progressing participants who started therapy six months sooner experienced a 3.4-year extension in event-free survival. Investigators noted that measurable strength improvement over time is rarely seen in ALS, making these observations clinically meaningful.
The most common adverse events were headache, procedural pain, fall, back pain and extremity pain. Serious neurologic events, including myelitis, radiculitis, papilledema, increased intracranial pressure, and aseptic meningitis, occurred in 8.7 percent of participants. These events were managed with standard care, and most resolved. Two cases resulted in treatment discontinuation. Overall findings were consistent with prior reports.
Timothy Miller said the VALOR data suggest that starting QALSODY earlier may provide meaningful benefits in SOD1-ALS, with some participants showing improvements in muscle strength over several years, something rarely seen in ALS. Merit Cudkowicz added that earlier treatment was linked with longer event-free survival, and she noted that the presymptomatic ATLAS study may help determine whether QALSODY can delay the onset of disease.
Merit Cudkowicz said the final results show what may be possible when QALSODY is started earlier in the course of SOD1-ALS. Among faster-progressing patients, beginning treatment six months sooner was linked with an additional 3.4 years of event-free survival. She added that these findings raise optimism for the ATLAS study, which is exploring whether starting therapy before symptoms appear could potentially delay disease onset.
How QALSODY Works
QALSODY is an antisense oligonucleotide designed to reduce production of mutant SOD1 protein, which contributes to motor neuron degeneration in SOD1-ALS. It is administered intrathecally: three loading doses at 14-day intervals, followed by maintenance dosing every 28 days.
The therapy received accelerated approval in the United States based on reductions in plasma neurofilament light chain. Continued approval depends on verification of clinical benefit in ongoing confirmatory studies. QALSODY is currently authorized in 44 countries under accelerated, conditional, or standard pathways.
Beyond the VALOR extension, the Phase 3 ATLAS trial is evaluating whether QALSODY can delay the onset of ALS when started before symptoms in individuals with a SOD1 mutation and elevated neurofilament. The primary outcome is time to clinically manifest ALS.
ALS is a progressive neurodegenerative disease that destroys motor neurons controlling voluntary movement. Most people lose the ability to speak, eat, move, and eventually breathe, with average survival of three to five years from symptom onset.
SOD1-ALS represents about 2 percent of all ALS cases, affecting roughly 330 people in the United States. Genetic forms of ALS may occur even without a known family history, highlighting the growing importance of genetic testing.
References
The Journal of the American Medical Association (JAMA) Neurology Publishes Long Term Results from the QALSODY Phase 3 VALOR Study and its Open-Label Extension in SOD1-ALS, 22 December 2025, https://investors.biogen.com/news-releases/news-release-details/journal-american-medical-association-jama-neurology-publishes
Miller TM, Cudkowicz ME, Shaw PJ, et al. Long-Term Tofersen in SOD1 Amyotrophic Lateral Sclerosis. JAMA Neurol. Published online December 22, 2025. doi:10.1001/jamaneurol.2025.4946
An Efficacy, Safety, Tolerability, Pharmacokinetics and Pharmacodynamics Study of BIIB067 (Tofersen) in Adults With Inherited Amyotrophic Lateral Sclerosis (ALS) (VALOR (Part C)), ClinicalTrials.gov ID NCT02623699, https://www.clinicaltrials.gov/study/NCT02623699?id=NCT02623699&rank=1
Long-Term Evaluation of BIIB067 (Tofersen), ClinicalTrials.gov ID NCT03070119, https://www.clinicaltrials.gov/study/NCT03070119?id=NCT03070119&rank=1