Related Experiment Video
Updated: Jul 11, 2026
ALS - Motor Neuron Disease: Mechanism and Development of New Therapies
Published on: July 29, 2007
Phase II/III randomized trial of TCH346 in patients with ALS
R Miller1, W Bradley, M Cudkowicz
1California Pacific Medical Center, San Francisco, CA 94115, USA. millerrx@sutterhealth.org
Insights
TCH346 did not show benefits for amyotrophic lateral sclerosis (ALS) patients. The drug, which targets apoptosis, failed to improve functional rating scale scores or other key outcomes in a large clinical trial.
Area of Science:
- Neuroscience
- Pharmacology
- Clinical Trials
Background:
- Apoptosis is a key pathogenic mechanism in neurodegenerative diseases like Amyotrophic Lateral Sclerosis (ALS).
- TCH346 is an antiapoptotic agent that binds to glyceraldehyde 3-phosphate dehydrogenase (GAPDH), potentially blocking apoptotic pathways.
Purpose of the Study:
- To evaluate the efficacy of TCH346 in slowing disease progression in patients with ALS.
- To assess the safety and tolerability of TCH346 at various dosages.
Main Methods:
- A randomized, double-blind, placebo-controlled trial involving 591 ALS patients across Europe and North America.
- Patients received placebo or TCH346 (1.0, 2.5, 7.5, or 15 mg/day) orally for at least 24 weeks, following a 16-week lead-in phase.
- Primary endpoint: rate of change in the revised ALS Functional Rating Scale (ALSFRS-R); Secondary endpoints: survival, pulmonary function, and manual muscle testing (MMT).
Main Results:
- No significant differences were observed in the mean rate of decline of ALSFRS-R between TCH346 treatment groups and the placebo group.
- Secondary outcome measures, including survival, pulmonary function, and MMT, also showed no significant differences between groups.
- The trial was adequately powered to detect a 25% reduction in ALSFRS-R decline.
Conclusions:
- The clinical trial provided no evidence for the beneficial effect of TCH346 on disease progression in patients with ALS.
- TCH346 did not demonstrate efficacy in this patient population, despite its proposed mechanism of action.
- Further research into TCH346 for ALS is not supported by these findings.
Background:
TCH346 exerts antiapoptotic effects by binding to glyceraldehyde 3-phosphate dehydrogenase (GAPDH) and blocking the apoptotic pathway in which GAPDH is involved. Apoptosis is considered to be a key pathogenic mechanism in neurodegenerative diseases including ALS.
Methods:
Patients were randomly assigned in a double-blind fashion to receive either placebo or one of four doses of TCH346 (1.0, 2.5, 7.5, or 15 mg/day) administered orally once daily for at least 24 weeks. The primary outcome measure was the rate of change in the revised ALS functional rating scale (ALSFRS-R). The trial design included a 16-week lead-in phase to determine each patient's rate of disease progression. The between treatment comparison was adjusted for the individual pretreatment rates of progression. The study was powered to detect a 25% reduction in the rate of decline of the ALSFRS-R as compared with placebo. Secondary outcome measures included survival, pulmonary function, and manual muscle testing (MMT).
Results:
Five hundred ninety-one patients were enrolled at 42 sites in Europe and North America. There were no differences in baseline variables. There were no significant differences between placebo and active treatment groups in the mean rate of decline of the ALSFRS-R or in the secondary outcome measures (survival, pulmonary function, and MMT).
Conclusion:
The trial revealed no evidence of a beneficial effect of TCH346 on disease progression in patients with ALS.
