Axcella’s phase 2a long COVID clinical trial has missed its primary endpoint. But with the study linking the drug to improved fatigue scores versus placebo, the biotech plans to meet with regulators to discuss its path to a registration trial.
Investigators randomized 41 subjects to receive either AXA1125, an orally active mixture of amino acids, or placebo twice a day for 28 days. At the end of the study, the phosphocreatine recovery rate (PCr) following moderate exercise was no better in the AXA1125 group than in the placebo cohort, causing the study to miss its primary endpoint.
Axcella picked PCr recovery time after exercise as the primary endpoint in light of evidence that it gives a validated and direct measure of skeletal muscle mitochondrial oxidative capacity. Based on earlier work, the biotech expected reductions in PCr recovery time to correlate to improved muscle function.
In discussing the primary endpoint data, the biotech said baseline PCr recovery time “among all subjects was significantly higher and had a higher degree of intersubject variability than previously reported in the literature.” As Axcella sees it, the baseline data “support the hypothesis that there is significant mitochondrial dysfunction in these patients but limits the utility of this parameter in a clinical trial.”
With the study missing its primary endpoint, Axcella focused its statement about the results on several secondary endpoints. Using the Chalder Fatigue Questionnaire (CFQ-11), Axcella linked AXA1125 to physical and mental improvements.
Recipients of AXA1125 reported mean changes in physical and mental CFQ-11 scores of -2.94 and -1.32, respectively, versus placebo. AXA1125 also beat placebo on the total CFQ-11 score, with a mean change versus placebo of -4.30.
“The statistically significant improvement in reported mental and physical fatigue among study participants receiving AXA1125 is a very encouraging finding for long COVID patients, who often experience extreme and constant fatigue throughout their day,” Betty Raman, associate professor at the University of Oxford and study leader, said in a statement.
Axcella also reported a significant improvement on the six-minute walk test. PureTech Health recently failed to improve walking distance in a larger study of its own potential long COVID drug, leading the company to drop plans for further development.