Yesterday, Wave Life Sciences announced that it ended its FOCUS-C9 clinical trial for the drug WVE-004, which was being evaluated as a potential treatment for FTD and amyotrophic lateral sclerosis (ALS) cases associated with a variation in the gene C9orf72, the most common genetic cause of FTD. Despite this news, AFTD applauds Wave Life Science for this groundbreaking basket trial, which used a single experimental treatment on multiple conditions and was the first clinical trial of a therapy that specifically targeted C9orf72-associated cases of both FTD and ALS.

“Wave Life’s first-of-its-kind trial of a C9orf72 therapy is a promising indication that the research community is on a clear path to developing treatments for FTD and ALS,” said AFTD CEO Susan L-J Dickinson, MSGC. “Although the trial ended early, our community should see FOCUS-C9 as a major step forward on that path, and one that redoubles AFTD’s commitment to continuing our collaborative, proactive work to make successful clinical trials happen in the ALS-FTD space.”

While the FOCUS-C9 trial did not find evidence of a clinical benefit for participants with either FTD or ALS, it did help to chart a promising path toward future treatments. It confirmed that even though FTD and ALS are less common than some other neurodegenerative diseases, clinical trials of new treatments are feasible, and that people living with these conditions are keen to participate in such research. In addition, reductions in a key biomarker of C9orf72-associated FTD and ALS, poly(GP), confirmed that the drug WVE-004 reached its target and was able to alter levels of this toxic protein in brain fluid. The FOCUS-C9 trial also demonstrated the value of biomarkers – an area of research actively supported by AFTD – to advance FTD and ALS drug development. Overall, WVE-004 was well-tolerated, with only mild side effects in most cases – a result with encouraging implications for future studies of this type of drug, known as an antisense oligonucleotide.

AFTD played an active role in supporting the FOCUS-C9 trial in partnership with the Alzheimer’s Drug Discovery Foundation (ADDF) through the Treat FTD Fund funding program. Specifically, AFTD funds were used to expand the trial to include exploratory fluid and digital biomarkers in addition to poly(GP) so that, regardless of the trial result, researchers would gain the necessary information to improve the chances of success of future studies.

As FTD and ALS are increasingly recognized to have commonalities at the molecular and clinical levels, AFTD has worked to expand its collaboration with stakeholders in the ALS field. This announcement will not deter these partnerships, and AFTD is looking ahead to support future trials. A second industry-sponsored trial of a drug for people with the C9orf72 variant, the Phase 2a study of the drug TPN-101 from Transposon Therapeutics, is currently underway. Research to better understand the causes of both genetic and sporadic FTD to identify novel targets for future drug development is also an active area of study. AFTD applauds Wave Life Sciences for its commitment to share FOCUS-C9 trial data results at an upcoming medical congress so that all researchers can learn from it.

AFTD continues to fund foundational science and drug development to help develop the next generation of therapies to be tested in clinical trials, including work to enable clinical trial infrastructure through activities such as convening experts in the field to tackle issues common to all FTD research at AFTD’s FTD Research Roundtable. Earlier this month, AFTD announced a new grant, the Digital Assessment Tools for FTD and ALS Awards, which will fund innovative ways to assess FTD and ALS symptom progression using digital tools such as smartphones and wearable trackers.

Other collaborations include AFTD contributions to comments on the NINDS Strategic Planning for ALS, participation in the ALS Association-led CReATe Consortium, the inclusion of ALS researcher leaders in the 2022 Holloway Summit, and participation on the steering committee of the inaugural Translational Neuroscience C9orf72 FTD/ALS Summit that was sponsored by the Barrow Neurological Foundation, David and Weezie Reese, and the Arizona Community Foundation.

These partnerships, and the willingness of companies like Wave Life Sciences to invest in clinical trials, give our community hope that we are closer than ever to finding a treatment for these devastating diseases.
AFTD asks that FOCUS-C9 trial participants contact their study site point of contact if they have any questions. People interested in staying up to date on FTD clinical trial opportunities are encouraged to enroll in the FTD Disorders Registry (ftdregistry.org).