Otsuka and Ionis have announced that ulefnersen, an investigational treatment for FUS-ALS, met its primary endpoint in the Phase 3 FUSION trial. It is the first FUS-ALS trial ever to do so.
The companies report:
The study met its primary endpoint, with ulefnersen demonstrating a statistically significant improvement on the primary endpoint assessing functional impairment and survival using a joint rank analysis of time to death or permanent ventilation, time to rescue* and change in ALS Functional Rating Scale Revised (ALSFRS-R) score from baseline to Day 505 compared to placebo (p=0.0005), providing evidence from the first-ever placebo-controlled clinical study targeting the underlying genetic cause of FUS-ALS.
The FUSION study also demonstrated statistically significant improvements favoring ulefnersen on secondary endpoints, including change from baseline in serum neurofilament light chain (NfL), and time to earliest of death, permanent ventilation, rescue, or withdrawal due to disease progression. Ulefnersen demonstrated a favorable safety and tolerability profile in people living with FUS-ALS, with most adverse events being mild or moderate in severity.
What is FUS-ALS?
FUS-ALS is a rare form of ALS caused by a change in a gene called FUS. It can affect people of any age, including teens and young adults, and it often progresses quickly. A genetic test is needed to confirm it, and there is currently no approved treatment that targets its cause.
In 2009, the FUS gene was discovered through a national collaboration directed by Dr. Teepu Siddique at the Les Turner ALS Center at Northwestern Medicine. The research was supported by the Les Turner ALS Foundation. This news shows how support for ALS research can lead, years later, to real treatment options for people living with ALS.
Important research into other forms of genetic ALS and sporadic ALS is currently underway at the Les Turner ALS Center — and your support makes that research possible, paving the way for potential breakthroughs like this one.
What happens next?
Ulefnersen remains an investigational treatment and is not currently approved for patient use. Further research and analysis is underway to ensure its safety and efficacy. The companies will continue their discussion with the FDA to expedited regulatory submission, though the drug is not yet approved or available.
Otsuka is establishing an ulefnersen early access program. The company recommends that people living with FUS-ALS and their caregivers should consult their treating physician to discuss whether participation in the ulefnersen early access program may be an option.
At the Les Turner ALS Foundation, we will continue to monitor the progress of this treatment. Sign up for our email list to ensure you receive the latest news and any opportunities for public comment.
Photo above: Discovered as part of a national collaboration led from the Les Turner ALS Center, the FUS/TLS gene mutation causes 5% of inherited cases of ALS.
