Almost all ALS cases share the pathological hallmark of TDP-43 protein aggregation in motor neurons. ION541 targets ataxin-2 RNA (ATXN2) which has been shown to prevent, or reverse, TDP-43 toxicity in preclinical models of ALS.

Amyotrophic Lateral Sclerosis aka Lou Gehrig’s Disease

ALS is a rare progressive and fatal neurodegenerative disorder that affects around 55,000 people worldwide. About 90% of ALS cases occur in people who have no apparent family history of the disease. People with ALS experience muscle weakness, loss of movement and difficulty breathing and swallowing resulting in a severely declining quality of life and potentially death. 

Frank Bennett, Ph.D., Ionis’ Chief Scientific Officer and franchise leader for neurological programs, stated, “As our third medicine designed to treat different forms of ALS to enter clinical trials, ION541 represents yet another example of the power of Ionis’ antisense technology to potentially target root causes of devastating neurodegenerative diseases. Initiation of ION541 clinical trial marks an important milestone in Ionis’ ALS program and reaffirms our commitment to the ALS community.”

Ionis received a payment of $10 million from Biogen for the initiation of this Phase 1/2 clinical trial of ION541.

Biogen is developing ION541 as part of a broad strategic collaboration with Ionis to advance novel antisense therapies for the treatment of neurological disorders.

Learn more at https://clinicaltrials.gov/ct2/show/NCT04494256?term=biib105&draw=2&rank=1.

Ionis Pharmaceuticals Other Investigational ALS Treatment Include the Following Therapies:

• Tofersen (BIIB067) is designed to reduce the production of superoxide dismutase 1 (SOD1), the cause of a genetic form of ALS, referred to as SOD1-ALS, that results from mutations in the SOD1 gene. SOD1-ALS is the second most common genetic form of ALS, accounting for up to 20 percent of genetic ALS. Tofersen is currently in Phase 3 clinical trial in SOD1-ALS patients with data expected in 2021.
• IONIS-C9Rx (BIIB078) reduces mutant C9ORF72 RNA and associated neurotoxicity. Mutations in the C9ORF72 gene account for greater than 30 percent of genetic ALS cases and five to 10 percent of all patients with ALS. It is the most common genetic form of ALS worldwide.

IONIS-C9Rx is the first drug in clinical development to specifically target the mutant C9ORF72 RNA and is a potentially first-in-class therapy for patients with C9ORF72-ALS, referred to as C9-ALS. IONIS-C9Rx has received Fast Track designation from the U.S. FDA. The product is currently in a Phase 1/2 trial in C9-ALS patients. 

Prohost Observations 

Prior to the genomic revolution one could never have dreamt of learning an explanation for ALS causes let alone about any serious treatment trials.

This is the second time we have posted news about treatments for this rare but debilitating and deadly disease in less then a month. The first was posted on page 7 in Prohost Letter #442 from September 28, 2020.

Today’s news is to inform about Ionis Pharmaceuticals’ third novel antisense ALS medicine – the first to treat a broad ALS population that has just started clinical trial.

The product to evaluate is ION541 (BIIB105) for the treatment of most forms of ALS regardless of family history.  

Biotechnology is finally realizing the dreams of humanity.

That’s great.

To read more about Ionis Pharmaceuticals please click here.