Experimental treatment may help preserve body weight in ALS, data show

AP-101, an experimental treatment being developed by AL-S Pharma for amyotrophic lateral sclerosis (ALS), may help patients preserve their body weight compared with a placebo, potentially indicating better clinical outcomes as the disease progresses.

These findings come from a post-hoc analysis of AP101-02 (NCT05039099), a completed Phase 2a clinical study that tested how safe AP-101 is when given as an infusion into the bloodstream and how well it works compared with a placebo in slowing ALS progression over about six months.

Confirmatory Phase 3 clinical testing is now expected to begin next year.

Angela Genge, MD, chief medical officer of AL-S Pharma, shared the data in an oral presentation at the 2026 Network of Excellence for ALS meeting, which is taking place this week in Clearwater, Florida, and online.

“Preservation of body weight is particularly relevant in ALS, where weight loss is closely associated with disease progression and poorer outcomes,” Genge said in a company press release.

Recommended Reading

Oct. 9, 2026 News by Marisa Horak, MS

Experimental treatment shows promise in patient with rare genetic form of ALS

Confirmatory Phase 3 study set to start in 2027

ALS is a progressive disease that damages motor neurons, the nerve cells that control muscles in the body. As these cells are lost, muscles become gradually weaker and start to waste away.

Exactly what causes ALS is not fully understood, but researchers believe that a combination of genetic and environmental factors play a role in driving the disease. For example, some patients carry mutations in the SOD1 gene, which lead to the formation of an abnormal SOD1 protein that forms toxic clumps inside nerve cells, ultimately causing their death. There are also some patients without SOD1 mutations who have misfolded SOD1, making this an important therapeutic target for ALS.

AP-101 is an antibody designed to bind to and clear misfolded forms of SOD1 while preserving the SOD1 protein, which helps protect nerve cells from damage. This is expected to prevent the spread of toxic SOD1, thereby helping to slow the progression of ALS symptoms.

The AP101-02 study included 73 adults with either sporadic ALS or with mutations in the SOD1 gene (SOD1-ALS). Participants were randomly assigned to receive either AP-101 or a placebo every three weeks for 24 weeks (about six months), on top of standard ALS treatment. After completing this randomized period, all patients entered an open-label extension in which they received AP-101 for another 24 weeks.

After data showed that AP-101 was safe and well tolerated, with meaningful benefits in measures of survival and noninvasive ventilatory support over up to one year, researchers conducted a post-hoc analysis of body weight trajectories.

The new analyses provide additional evidence that rate of weight loss is an important additional measure of clinical response alongside established functional, respiratory, and survival outcomes.

In ALS, weight loss has been linked to shorter survival. The new analyses showed that patients treated with AP-101 generally maintained their body weight better than those receiving a placebo.

In the group with sporadic ALS, the difference in body weight between the AP-101 and placebo groups increased over time, favoring AP-101. After six months, the adjusted difference between the two groups was 2.25 kg, or about five pounds. In SOD1-ALS patients, the difference favored AP-101 by 4.82 kg, or about 10.6 pounds, 21 days (about three weeks) after the randomized period.

The benefit was also observed in patients with high levels of misfolded SOD1 in their cerebrospinal fluid, the clear liquid surrounding the brain and spinal cord. Among those with sporadic ALS with the highest levels of misfolded SOD1, the difference in body weight favored AP-101 by 4.59 kg, or about 10 pounds, at the same 21-day follow-up visit.

The company is now planning to launch a larger Phase 3 study to confirm the findings. The study is planned to enroll up to 300 adults with ALS, who will be randomly assigned to receive either AP-101 or a placebo, alongside standard care, every three weeks for one year. Researchers will assess changes in physical function, survival, and other measures, such as body weight, breathing, and quality of life.

“The new analyses provide additional evidence that rate of weight loss is an important additional measure of clinical response alongside established functional, respiratory, and survival outcomes. We are eager to progress the confirmatory Phase 3 study with the intention of delivering a critically needed new treatment option targeting misfolded SOD1 to people living with ALS,” Genge said.