New ALS treatment improves survival, leads to function gains in trial
Data show rare 'objective evidence' of disease modification with AP-101
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- The ALS therapy candidate AP-101 significantly extended patient survival and delayed the need for respiratory support in a Phase 2 clinical trial.
- Additionally, researchers say the infusion therapy may target underlying disease mechanisms in ALS.
- A confirmatory Phase 3 study is planned for this promising ALS treatment, per developer AL-S.
Early treatment with AL-S Pharma‘s infusion therapy AP-101 significantly extended survival and delayed the need for respiratory support in people with amyotrophic lateral sclerosis (ALS), compared with a six-month delay in starting therapy, new trial data show.
The therapy candidate is being developed to target and clear the misfolded SOD1 proteins that form toxic clumps in some people with ALS.
Among trial participants, the improved survival outcomes were accompanied by improvements in functional ability in some patients, as well as reductions in key markers of nerve cell death.
That’s according to the new data from the Phase 2a clinical trial (NCT05039099), which were presented last week by Angela Genge, MD, chief medical officer of AL-S Pharma, at the AD/PD 2026 International Conference on Alzheimer’s and Parkinson’s Diseases.
Following the positive Phase 2 data, AL-S Pharma is now planning to launch a confirmatory Phase 3 study, which is expected to begin later this year.
“These data show something we rarely see in ALS – objective evidence of clinically meaningful disease modification that tracks directly with prolonged survival,” Genge said in a company press release.
While the mechanisms that drive ALS aren’t fully understood, some cases are associated with mutations in the gene that encodes the SOD1 protein. These mutations, which are found in as many as 20% of people with familial ALS and 2% of those with sporadic ALS, cause the SOD1 protein to misfold and clump up, which is thought to contribute to nerve damage and ALS progression. ALS is known as familial when it affects more than one person in the same biological family; it’s called sporadic when there’s no known family history.
Although generally associated with SOD1 mutations, misfolded SOD1 protein has also been seen in some ALS patients without a SOD1 mutation.
AP-101 designed to clear toxic protein clumps in ALS
An antibody therapy, AP-101 is designed to bind to misfolded SOD1 and clear the toxic protein from the nervous system, thus helping to preserve motor neurons. Those specialized nerve cells are essential for both voluntary movement, such as walking, and involuntary actions, including breathing.
The Phase 2a study tested AP-101 against a placebo in 73 adults with sporadic or SOD1-related familial ALS. In the first six months, participants were given either AP-101 or the placebo. Then, for the next six months, everyone was treated with AP-101.
The study’s main goal was to evaluate the treatment candidate’s safety profile. Top-line results announced by AL-S Pharma last year showed that AP-101 was safe and well tolerated among participants.
The therapy also reduced two markers of nerve damage, namely blood levels of neurofilament light chain (NfL) and spinal fluid levels of phosphorylated neurofilament heavy chain (pNfH).
The new analyses now show that the time to death or requiring ventilation was significantly prolonged among patients who received AP-101 at the study’s start compared with those given the placebo. Those findings indicate that early treatment may help extend survival.
Significant differences were seen both for patients with sporadic and SOD1-related familial ALS, according to the researchers.
At AL-S Pharma, we believe AP-101 could fundamentally transform the treatment of ALS.
These effects on survival were accompanied by a stabilization in disease stage, and by reductions in ALS Functional Rating Scale Revised (ALSFRS-R) scores, indicating improved function, in people with elevated levels of misfolded SOD1 at trial start and in those carrying SOD1 mutations.
“The Phase 2 study results with AP-101 are consistent with the hypothesis that targeting misfolded SOD1 is a disease-modifying approach in ALS,” Genge said. “At AL-S Pharma, we believe AP-101 could fundamentally transform the treatment of ALS. We look forward to continue advancing the AP-101 clinical program so that we can bring a much-needed new treatment option to people living with ALS rapidly.”
