Trial of potential oral ALS treatment completes enrollment in China
Researchers will assess whether experimental therapy slows functional decline
Written by |
- ALS is a progressive disease that damages and destroys motor neurons, leading to worsening muscle weakness, loss of physical function, and breathing difficulties.
- Neuronal hyperexcitability, in which nerve cells become overactive, is thought to contribute to motor neuron damage in ALS.
- A Phase 2/3 trial of CB03-154, an experimental oral therapy designed to calm overactive motor neurons, has completed enrollment in China.
A pivotal Phase 2/3 clinical trial comparing the experimental oral therapy CB03-154 with a placebo in people with amyotrophic lateral sclerosis (ALS) has completed enrollment in China, developer Zhimeng Biopharma announced.
China’s Center for Drug Evaluation (CDE) cleared the trial to begin last year. It is led by Fan Dongsheng, MD, PhD, who directs the neurology department at Peking University Third Hospital. The trial has now enrolled 255 people with ALS, ages 18 to 65, at 15 clinical research centers across China.
Trial will measure changes in patients’ everyday abilities
The trial’s main goal is to determine whether CB03-154 can slow the loss of abilities needed for daily activities, such as walking, speaking, and swallowing. Researchers will assess this by measuring changes in scores on the Revised ALS Functional Rating Scale (ALSFRS-R) after 39 weeks, or about nine months.
“The completion of patient enrollment for the pivotal Phase 2/3 clinical trial of CB03-154 marks a strategically significant milestone for Zhimeng Biopharma in the field of ALS treatment,” Huanming Chen, PhD, founder and CEO of Zhimeng, said in a company press release. “I would like to extend my sincere appreciation to Professor Fan Dongsheng and the investigators at all clinical research centers across China for their dedicated efforts, as well as to all ALS patients and their families who participated in the trial for their selfless commitment.”
Zhimeng expects Phase 2 topline results in the third quarter of 2027. If the findings are positive, the company plans to seek conditional approval of CB03-154 for ALS in China. If granted, conditional approval could give patients earlier access to the treatment while the company conducts additional studies required by Chinese regulators.
In the U.S., CB03-154 has received orphan drug status for ALS. This designation offers incentives for developing treatments for rare diseases, which generally affect fewer than 200,000 people in the U.S.
ALS damages and destroys motor neurons, the nerve cells that control movement. This leads to worsening muscle weakness and other symptoms. Although several approved treatments can help manage symptoms or slow disease progression, ALS has no cure.
The causes of ALS are still not fully understood, but neuronal hyperexcitability is thought to play a role. This happens when nerve cells become active too easily and send electrical signals more often than they should. The extra activity may place stress on these cells and contribute to their damage.
Experimental therapy aims to calm overactive nerve cells
CB03-154 is designed to reduce this excessive nerve cell activity by opening potassium channels formed by two proteins called KCNQ2 and KCNQ3. These channels help control how easily nerve cells become active by allowing electrically charged potassium particles to flow out of the cells. By opening these channels, CB03-154 aims to calm overactive motor neurons and potentially protect them from further damage.
The therapy is designed to act selectively on KCNQ2 and KCNQ3, with little effect on other types of channels. Researchers hope this targeted approach will help limit unwanted side effects.
Earlier laboratory studies showed that CB03-154 reduced excessive activity in motor neurons derived from people with ALS, bringing their activity closer to that of healthy cells. In mice with ALS-like disease, CB03-154 improved movement, extended survival, and increased the speed at which nerve signals traveled. These findings suggest it may help protect motor neurons from damage.
In a Phase 1 trial in Australia involving 56 healthy volunteers, CB03-154 was generally safe and well tolerated at single doses up to 30 mg and daily doses up to 20 mg for 14 days. The most common treatment-related side effects were dizziness, sleepiness, and headache. Most adverse events reported during the study were mild.
Researchers testing three doses of CB03-154 in ALS trial
Building on these findings, the ongoing Phase 2/3 trial (NCT07082192) is testing CB03-154 in people living with ALS. Participants were randomly assigned to receive one of three daily oral doses of CB03-154 (5, 10, or 15 mg) or a placebo for 39 weeks.
In addition to changes in ALSFRS-R scores, researchers will assess whether CB03-154 affects survival, the need for long-term breathing support, and lung function. Researchers will also track changes in disability, symptoms of depression, and quality of life. They will measure blood levels of neurofilament light chain (NfL), a marker of nerve cell damage.
After the initial 39 weeks of treatment, participants may enter an additional 39-week period called an open-label extension, during which everyone will receive CB03-154. The goal is to continue assessing its safety and effectiveness over a longer period of time.
“Moving forward, we will spare no effort to advance clinical development and regulatory submissions, striving to bring a truly effective new treatment option to ALS patients in China and around the world as soon as possible,” Chen said.
Leave a comment
Fill in the required fields to post. Your email address will not be published.