The TEALS (Tecfidera in amyotrophic lateral sclerosis) study was a multi-centre Phase 2 clinical trial to investigate the safety, tolerability and effectiveness of a drug called Tecfidera in people with MND.
Tecfidera is currently used to treat relapsing multiple sclerosis and works by dampening down inflammation. A variety of neuroinflammatory changes occur in people with MND including a reduction in immune cells known as regulatory T cells. Reductions in regulatory T cells have been associated with a rapid rate of disease progression in MND. In animal models of MND, increasing levels of regulatory T cells has been beneficial to survival. In humans, Tecfidera enhances regulatory T cell levels, so the investigators hope to slow down MND disease progression by targeting this pathway.
The TEALS Study assessed whether Tecfidera is effective in slowing down disease progression and whether it is safe in MND patients.
The results were published in September 2021. The trial results showed Dimethyl fumarate (Tecfidera), in combination with riluzole, was safe and well-tolerated in ALS. There was no significant improvement in the primary endpoint. The trial provides class I evidence for safety and lack of efficacy of dimethyl fumarate in ALS.
Contributing factors beyond the lack of efficacy of Tecfidera could have been the unexpectedly small decline in ALSFRS-R over the course of the trial, especially compared to other clinical trials. Other trials have selected for “fast-ALS progressors,” which the present study did not. This could explain the absence of clinical significance and lower rates of ALSFRS-R decline in the current trial. Future clinical trials could perhaps assess dimethyl fumarate efficacy in “fast progressing” ALS patients.
The TEALS Study was led by Professor Matthew Kiernan (University of Sydney, Brain and Mind Centre) and Professor Steve Vucic (University of Sydney, Westmead Hospital).
The six centres were:
At the time of recruitment, participants must have been diagnosed with sporadic amyotrophic lateral sclerosis for less than two years. In addition, the study only enrolled patients who are on a stable dose of riluzole for at least 30 days prior to the screening visit.
Tecfidera is a tablet taken orally with food. Patients were randomised into a treatment group and a placebo group so not all participants will receive the active drug. Patients were assessed for safety, clinical and neurophysiological outcome measures. The study duration was 42 weeks.
The trial design is described in detail here.
This research will determine if Tecfidera is effective and safe in MND. Analysis of data from the trial will give researchers a clearer picture on whether Tecifdera should be tested in larger studies to further investigate its potential.
For more information, contact Professor Steve Vucic.
Further information is available here