Isis Pharma’s ALS Candidate Drug Enters Clinical Trial

ISIS Pharmaceuticals, in collaboration with Biogen, has started a Phase 1/2 clinical study of ISIS-SOD1_Rx (BIIB067), one of the drug candidates to come out of the strategic partnership between the two companies, in adult patients diagnosed with amyotrophic lateral sclerosis (ALS).

ISIS-SOD1_Rx’s mode of action relies on ISIS antisense technology that targets at a genetic level the production of the superoxide dismutase 1  protein and its mutant form, the second most common inherited form of ALS, believed to account for up to 20 percent of all familial ALS cases. Several studies have shown that mutations in this gene lead to a toxic gain of function that results in progressive loss of motor neurons, symptoms such as muscle weakness and loss of movement and eventually ALS diagnosis.

C. Frank Bennett, Ph.D., senior vice president of research at Isis Pharmaceuticals, commented in a press release, “We have previously demonstrated that we can safely administer an antisense drug in patients with familial ALS by intrathecal injection.  In the study initiated today, we are evaluating a more potent antisense drug designed to directly reduce the production of the SOD1 protein.  This approach has the potential to provide therapeutic benefit to patients with SOD1-ALS by slowing or even halting progression of this fatal disease.”

The randomized placebo-controlled clinical trial, which is not yet recruiting, will evaluate the safety, tolerability, and pharmacokinetics of the drug in adults with ALS (primary endpoint). As a secondary endpoint, the study will evaluate the effect of ISIS-SOD1_Rx (BIIB067) in the levels of superoxide dismutase 1 (SOD1) protein in patients’ cerebrospinal fluid (CSF), where the drug will be directly injected.

Lynne Parshall, chief operating officer of Isis Pharmaceuticals, also commented on the announcement, “Together with Biogen, we have made significant progress developing antisense drugs to treat neurological and neuromuscular disorders.  The advancement of ISIS-SOD1_Rx into clinical development is an important milestone for this collaboration and reflects Biogen’s and our commitment to developing drugs for patients with ALS.  The advancement of this program is also another example of the broad applicability of our technology to address diseases that are unapproachable by other therapeutic modalities.”