MND Australia

VALOR (Tofersen)

Phase 1/2/3

What is the VALOR study?

The VALOR study is a 3-part trial to examine the efficacy, safety, tolerability, PK (pharmacokinetics) and PD (pharmacodynamics) of BIIB067. Part A is the single ascending dose (SAD) component of the study, Part B is the multiple ascending dose (MAD) component of the study and Part C is the fixed dose component of the study. Hence, the overall phase of development of the study is 1/2/3. In total, the study is estimated to enrol 183 participants, with 99 in Part C.

Approximately 10 percent of all ALS cases are genetic and about a fifth of those are caused by SOD1 gene mutations which is the second most common cause of genetic ALS. Tofersen is an antisense oligonucleotide, that works by targeting and reducing protein created by mutated SOD1. The mutated protein is toxic and leads to ALS by damaging the nerve cells that control movement. Tofersen aims to decrease the production of the mutant protein.

Parts A and B were completed in Jan 2019. Analysis of this data showed promising results which were announced in May 2019.

This component of the study involved 50 people with ALS who had an SOD1 genetic mutation. Participants received five doses of either 20, 40, 60 or 100 milligrams (mg) of the experimental drug or a placebo, through a lumbar puncture, or spinal tap, over approximately 3 months. Researchers examined the safety, dosage and exploratory efficacy of the experimental drug.

Researchers found that the 10 people who were given 100 mg of the experimental drug had a 37 percent reduction of the SOD1 protein in spinal fluid when compared to 12 people who received the placebo.

What is involved?

Consequently, Biogen has initiated Part C which is a phase 3 clinical trial. The trial is now enrolling and aims to enroll approximately 100 people with SOD1 ALS. The trial will last 32 weeks and participants will receive 8 doses of the drug or a placebo. There is a 1-in-3 chance of being assigned to the placebo group. In Australia the VALOR trial is being conducted by Professor Steve Vucic at Westmead hospital. The trial is only open to those patients carrying the SOD1 genetic mutation. Please discus your suitability for this trial with your neurologist.

How far off is a treatment?

This study will determine if tofersen is effective and safe in MND. Analysis of data from the trial will give researchers a clearer picture on whether Tofersen has the potential to be an effective therapeutic option for those aptients carrying the SOD1 mutation. Even if the trial is a success it is likely several years before Tofersen would be available as a treatment.

Update from the Scientific Advisory Council

MND Australia is a member of the International Alliance of ALS/MND Associations. One of the resources of the International Alliance is the Scientific Advisory Council (SAC). Click here to read the latest Tofersen briefing notes from the SAC.

For more information contact Professor Steve Vucic.