Axcella Therapeutics, founded by the same incubator as Moderna, will test its midstage investigational drug for NASH in patients with muscle fatigue and weakness who have survived COVID-19. The biotech has teamed up with the University of Oxford for a phase 2a trial.
The treatment prospect for so-called "long COVID," in which symptoms last for months following recovery from the pandemic disease, will be compared against placebo in about 40 patients in the U.K. twice a day for 28 days starting later this year, Axcella said Tuesday. The Cambridge, Massachusetts-based biotech is already investigating the drug in a phase 2b study in patients with nonalcoholic steatohepatitis (NASH), the most severe case of fatty liver disease.
The dry powder drug, dubbed AXA1125, is meant to treat chronic fatigue and muscle weakness, some of the most common symptoms of long COVID, which is also referred to as Post COVID-19 Condition and Post-Acute Sequelae of COVID-19 (PASC). One study, by Penn State researchers, found that more than half of 236 million people who have been diagnosed with COVID-19 end up experiencing long COVID up to six months following recovery.
The primary goal of the drug is to improve mitochondrial function within skeletal muscle by measuring changes in phosphocreatine recovery time. That endpoint is "validated in a series of diseases that have correlations into fatigue and muscle weakness," said Bill Hinshaw, CEO and president, in an interview with Fierce Biotech. This includes amyotrophic lateral sclerosis, Duchenne muscular dystrophy and chronic kidney disease. The trial will also look at a six-minute walk test, levels of fatigue and safety and tolerability of the oral drug, which is poured into four-to-six ounces of water, Hinshaw added.
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In preclinical studies and two clinical trials, AXA1125 showed the ability to restore homeostasis and mitochondrial function, or, as high schoolers know it, the "powerhouse of the cell." Hinshaw compared it to a battery.
"The virus actually damages the battery, so it cannot hold the charge and it cannot restore the charge quickly enough. The human element of this is you have patients who are debilitated," Hinshaw said. So, AXA1125 aims to repair the battery and "ideally, supercharge it," the CEO said.
Axcella will test the drug in patients who were diagnosed with COVID-19 at least 12 weeks prior and the trial is slated to have a data readout by mid-2022 with a potential registrational trial expected to happen quickly thereafter, Hinshaw said. The company has had "exceptional conversations" with the U.K.'s regulatory body, the Medicines and Healthcare products Regulatory Agency, he said, noting he believes "the regulators are very eager" for a treatment for long COVID.
With the trial in hand, Axcella will then follow up "with the FDA related to the chance for accelerated approval." The company is engaging with U.S. institutions like Mount Sinai, UCLA, the Institutes for Systems Biology and others about development in Axcella's home country.
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“With the progress in vaccination and acute treatments, that’s phenomenal and important contributions of the life sciences industry; at the same time, there’s very little development in long COVID and very little in fatigue and muscle weakness," Hinshaw said.
PureTech Health is another biotech looking at long COVID, with a phase 2 trial testing its most advanced drug candidate in patients with respiratory complications from the disease. The drug is also being studied in patients with breast cancer-related, upper limb secondary lymphedema.
Atea Pharmaceuticals is also exploring a follow-on study of its Roche-partnered SARS-CoV-2 antiviral in 1,000 patients with long COVID, the biopharma said in August.
While Moderna President Stephen Hoge sits on Axcella's board and has "pushed us very hard to really go out and help these patients," Hinshaw said it's unlikely the two companies will collaborate on the long COVID treatment since Moderna's pandemic efforts revolve around its mRNA vaccine.