EXPERTS-ALS interim results strengthen use of NfL as robust trial biomarker
MND/ALS research continues to accelerate, and recent developments reinforce the breakthrough achieved with Qalsody (tofersen) for SOD1 MND/ALS.
Tofersen is now approved by the MHRA in the UK, with NICE due to pronounce on NHS availability this month. In the meantime, Biogen is providing access through its global Expanded Access Programme (EAP) despite some troubling regional issues in the UK.
Tofersen was the first treatment to significantly lower neurofilament light chain (NfL), the leading biomarker of active neurodegeneration, by 50 to 60% in MND/ALS, establishing a clear biological effect which was matched with truly positive clinical changes.
Now, the momentum is building further with:
• A new ASO therapy, ulefnersen (formerly Jacifusen) for FUS‑ALS, from Ionis, showing significant and meaningful NfL reduction reported in a recent press release and positive clinical effect especially within in the EAP.
• The Mayo Clinic (Florida) reporting on an experimental ASO, developed by n-Lorem, in a single case (known as a n of 1 study), for an ultra rare form of MND/ALS, the causative gene CHCHD10. Early press releases have stated significant NfL lowering alongside clinical stability*.
Taken together, these recent results strengthen the continuing growing evidence that NfL reduction in a trial is a powerful indicator of genuine disease modifying activity.
*It is important to note that these early result findings are subject to confirmation.
EXPERTS‑ALS continues its rapid triage with rapid clarity
In its latest update the EXPERTS‑ALS drug screening platform, the flagship project of the UK MND Research Institute, has now reported ropinirole as futile, meaning that the drug candidate does not meaningfully slow the disease process in MND/ALS.
Although disappointing, this is exactly the intention/ambition of the screening platform. In under two years, EXPERTS‑ALS has now ruled out three drugs. Its design, with a laser focus on a single biomarker (NfL), Bayesian adaptive protocol, and small cohorts of 50 to 80 patients all receiving active drug, enables fast and decisive efficacy signal detection/futility. We clearly all hope that the opposite now happens with positive NfL reduction signals in the future.
The lead investigators of EXPERTS-ALS have also published their thoughts on the latest results. It’s worth a read.
What comes next?
A natural next step is to explore how EXPERTS‑ALS and MND‑SMART, the UK’s adaptive shared placebo efficacy platform, might complement one another. With EXPERTS‑ALS rapidly screening for in-human biologically active candidates, and MND‑SMART designed for longer, more detailed efficacy/safety testing, there is a clear opportunity to consider how these strengths could have synergy.
This could open a route to a more streamlined, efficient trial ecosystem in the UK that benefits patients now and builds a stronger pipeline for the future.
United2EndMND
