New Data Show Potential of Investigational Drug for Genetic Form of ALS


An investigational therapy for amyotrophic lateral sclerosis has shown promise in slowing the progression of the disease in patients with a genetic form of the disease.

An investigational therapy for amyotrophic lateral sclerosis (ALS) has shown potential in slowing the progression of the disease in patients who have an a superoxide dismutase 1 (SOD1) mutation in an early-stage clinical trial, according to data presented at the American Academy of Neurology’s (AAN) 71st Annual Meeting in Philadelphia, held May 4 to May 10, 2019.

In ALS, approximately 10% of cases are genetic and approximately one-fifth of those are caused by SOD1 gene mutations, according to AAN.

The phase 1/2 study of tofersen, an antisense oligonucleotide (ASO), is evaluating the drug in 70 patients with ALS who have a confirmed SOD1 mutation. For the study, the researchers examined the safety, dosage, and exploratory efficacy of tofersen. In the multiple ascending dose portion, 50 patients with SOD1 mutations were randomized to receive tofersen 20 mg, 40 mg, 60 mg, 100 mg, or a placebo for 12 weeks.

“The treatment that we researched in this study, an antisense oligonucleotide called tofersen (BIIB067), works by targeting and reducing protein created by the mutated gene,” study author Timothy M. Miller, MD, PhD, of Washington University School of Medicine in St Louis, said in a press release. “The mutated protein is toxic and leads to ALS by damaging the nerve cells that control movement. Our research aimed to decrease the production of that protein.”

Over a 3-month period, treatment with tofersen 100 mg resulted in a statistically significant lowering of SOD1 protein levels in the cerebrospinal fluid and a numerical trend toward slowing of clinical decline as measured by the ALS Functional Rating Scale-Revised (ALSFRS-R), slow vital capacity, and muscle strength compared with a placebo, according to the interim data. The mean change in ALSFRS-R score from baseline to Day 85 was -1.1 in the tofersen 100 mg group compared with -5.3 in the placebo group, on a 48-point scale.

Lower concentrations of the protein in the spinal fluid are indicative of lower concentrations in the brain and spinal cord as well, Dr Miller added. He noted that these reductions could lead to the preservation of motor neurons and slow progression of the disease, but more research is needed.

“The interim results of this study, which achieved proof-of-biology and proof-of-concept, support the initiation of a phase 3 clinical trial to confirm the efficacy and safety of tofersen in SOD1-ALS patients and further demonstrate the potential of ASOs to target the genetic driver of the disease,” Michael Ehlers, MD, PhD, executive vice president of research and development at Biogen, said in a statement. “We are committed to bringing a potential breakthrough therapy to patients with ALS and we are expediting our efforts with the aim of addressing this urgent unmet need.”

The most common adverse effects reported in the trial were mild to moderate and included headache, pain due to the procedure, and post lumbar puncture syndrome, according to Biogen.

The study authors acknowledged that the small number of participants and short time frame presented limitations for the study. More studies in larger groups of patients and spanning longer durations of time are needed to validate the findings.

Moreover, Biogen recently initiated the VALOR phase 3 clinical trial to confirm the efficacy and safety of tofersen in patients with SOD1-ALS. The first patient in this study was dosed in March 2019, according to Biogen.


Experimental Drug Shows Promise for Genetic Form of ALS [news release]. American Academy of Neurology. Accessed May 7, 2019.

Biogen to Present New Interim Data from its Phase 1/2 Clinical Study of Tofersen (BIIB067) for the Potential Treatment of a Subtype of Familial Amyotrophic Lateral Sclerosis (ALS) [news release]. Biogen. Accessed May 7, 2019.

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