Experimental ALS therapy QRL-201 shows potential to slow disease decline
Interim data suggest treatment protects nerves by restoring a vital protein
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- Experimental therapy QRL-201 shows potential to slow ALS progression by restoring a vital nerve protein.
- Interim Phase 1/2 data indicate that QRL-201 restores Stathmin-2 levels, reduces nerve damage, and improves daily function.
- The treatment was safe and well tolerated, with a Phase 3 trial planned for 2027.
The experimental therapy QRL-201 successfully reached its biological target and showed early signs that it may slow disease progression in people with sporadic amyotrophic lateral sclerosis (ALS), according to new Phase 1/2 trial data.
These interim results from the proof-of-concept ANQUR trial (NCT05633459) suggest the treatment can restore a critical protein needed for nerve health, marking a significant step toward a potential new “precision medicine” for the condition. The trial is testing the safety and preliminary efficacy of multiple doses of QRL-201 in people with sporadic disease.
Based on these promising findings, developer Quralis is moving forward with an open-label extension study, which has been approved in Canada and is under review in other regions, and is already preparing for a pivotal Phase 3 trial scheduled for 2027. The data offer hope for the majority of ALS patients who lack effective options to halt the underlying nerve damage caused by the disease.
“Our mission is to make a meaningful difference for people living with ALS. We believe QRL-201 has the potential to modify disease progression and improve outcomes for sporadic ALS patients,” Kasper Roet, PhD, CEO and co-founder of Quralis, said in a company press release.
Restoring the Stathmin-2 protein
The vast majority of people with ALS have problems with a protein called TDP-43. While TDP-43 is normally needed in the nucleus to do its job, in ALS nerve cells, it leaves the nucleus and forms toxic clumps.
TDP-43 is essential for processing messenger RNA (mRNA), which is transcribed from genes and serves as a template for protein production. It is particularly involved in a process called splicing, in which mRNA molecules are edited to produce correct proteins.
One of the most important proteins affected when TDP-43 is missing from the nucleus is Stathmin-2 (STMN2), a protein essential for nerve stability and repair and for healthy neuromuscular junctions, which are the contact points where nerves communicate with muscles.
Given as an injection into the spinal canal, QRL-201 is an antisense oligonucleotide, which is a short strand of genetic material designed to bind STMN2‘s mRNA molecule and restore its normal processing. This is expected to increase STMN2 levels, easing ALS symptoms and slowing disease progression.
The ANQUR clinical trial is testing QRL-201 in 69 adults with sporadic ALS. Seventeen patients were included in the already completed dose-escalation phase, and the other 52 patients entered the dose-range finding phase, which is testing two different doses of QRL-201.
Results from tissue tests have now shown that the treatment reached its intended target in the spinal cord and motor cortex, the area in the brain that controls movement. Levels of STMN2 increased to above the estimated therapeutic target. The treatment also corrected the splicing of STMN2’s mRNA.
In the group of patients treated with the lower dose, there was a significant reduction in phosphorylated neurofilament heavy chain, a biomarker of nerve cell damage. Patients also showed a trend toward slower worsening on the ALS Functional Rating Scale Revised (ALSFRS-R), a measure of daily function in ALS, particularly in gross motor function.
An additional post-hoc analysis excluded patients with very high levels of neurofilament light chain, which is linked to faster disease progression. It showed a statistically significant slowing of ALSFRS-R decline after about six months with QRL-201 compared with a placebo. Overall, QRL-201 was safe and well tolerated, with most side effects being mild or moderate.
“I am encouraged by these data from the ANQUR clinical trial of QRL-201. The combination of effects … is very promising and remarkable to see from an early stage clinical trial,” said Merit E. Cudkowicz, MD, director of the Sean M. Healey & AMG Center for ALS and executive director of the Mass General Brigham Neuroscience Institute in Boston.
For Roet, these data “are well aligned with our understanding of STMN2 biology and the potential of STMN2 restoration to have a positive impact on ALS disease progression.”
“We are grateful to the ANQUR clinical trial team, participants and their families, and look forward to advancing the QRL-201 clinical program to deliver a much-needed precision medicine option for people living with ALS,” he added.
