IONIS-SOD1Rx (BIIB067) is an investigational therapy to slow the progression of familial amyotrophic lateral sclerosis (ALS). It is being developed in a collaboration between Ionis Pharmaceuticals (previously Isis Pharmaceuticals) and Biogen.

It is administered as an injection directly into the spinal fluid, also known as an intrathecal injection.

How IONIS-SOD1Rx works

ALS is a fatal, progressive neurodegenerative disorder, where damage to and death of motor neurons (nerve cells that control the movement of muscles) lead to a loss of muscle control and paralysis. The exact cause of the disease is unknown, but some inherited forms of ALS are due to a mutation in the superoxide dismutase 1 (SOD1) gene. This mutation changes the way SOD1 functions, causing it to become toxic and leading to a rapid loss of motor neurons.

IONIS-SOD1Rx is a type of antisense therapy. It is designed to specifically bind to the SOD1 mRNA (a copy of the gene that is used by the protein making machinery of the cell to make SOD1 protein) and prevent it from being read, therefore stopping the production of toxic SOD1 protein. By reducing levels of toxic SOD1 protein, it is hoped that IONIS-SOD1Rx could slow the progression of this form of ALS.

IONIS-SOD1Rx in clinical trials

A Phase 1 clinical trial (NCT01041222) assessing the safety, tolerability, and activity of IONIS-SOD1Rx in SOD1-related familial ALS patients has been completed. The randomized, double-blind, placebo-controlled trial tested four different doses of IONIS-SOD1Rx in 33 patients who received either 0.15 mg, 0.5 mg, 1.5 mg, or 3 mg of the treatment over a 12-hour period. The patients were then assessed for 28 days following treatment. No serious adverse effects were observed in response to IONIS-SOD1Rx treatment, and the most common side effects were post-lumbar puncture syndrome (PLPS), also known as spinal headache, back pain from the injection, and nausea. The results are published in the medical journal Lancet Neurology.

Following this, a second and larger Phase 1 trial (NCT02623699) has been initiated. The trial aims to enroll 72 patients and is currently recruiting participants. The randomized, placebo-controlled trial aims to confirm the safety and tolerability of IONIS-SOD1Rx. Furthermore, the trial will measure levels of SOD1 in the spinal fluid of patients to evaluate if this may influence the response to treatment. Patients who complete the study will be invited to participate in another study (NCT03070119) evaluating the long-term safety and tolerability of IONIS-SOD1Rx.

Other information

IONIS-SOD1Rx received orphan drug designation from the European Medicines Agency (EMA) on Aug. 29, 2017.

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