'We beg you': Biotechs plead for help and funds to find long COVID treatments

Behind the unrelenting challenges of long COVID, which leaves many of the disease’s sufferers with exhaustion, sleep problems and brain fog, is just a handful of biotechs trying to drum up interest—and funds—to find a treatment.

“We know you're suffering and we are working as hard as we can to get this study up and running,” said Margaret Koziel, M.D, Chief Medical Officer at Axcella Therapeutics. “It's not been easy.”

That was the takeaway from an hours-long seminar on long COVID hosted Tuesday by the Biotechnology Innovation Organization (BIO), a lobbying and advocacy organization for the biopharma industry. The roundtable left few stones unturned, convening epidemiologists, patient advocates, federal health officials and drug manufacturers.

Underscoring the difficulty in treating long COVID is uncertainty in how many patients even have the disease. A November 2021 modeling estimate from the CDC put the figure between 3-5 million adults. But the agency’s more recent household pulse survey estimated that 15% of all adults have experienced long COVID.

Koziel’s candid statement is an understatement. Axcella laid off 85% of its staff at the end of 2022 to focus resources on long COVID. The drug now sewn to the hip of the company is AXA1125, which failed its latest phase 2 trial assessing the phosphocreatine recovery rate (PCr) following moderate exercise in treated patients compared to placebo. But the company found an encouraging enough signal in improving fatigue that it’s persevering. 

Now, Axcella has a phase 2/3 trial that has been green-lit in the U.K. and U.S., but the biotech needs more money. 

“We are presently looking for funding to start the study and complete the study,” said Koziel. 

The message was echoed by AIM Immunotech CEO Thomas Equels, whose company is trialing one of its top assets, Ampligen, in long COVID. Ampligen has already been tested in patients with chronic fatigue, with a confirmatory phase 3 trial slated to launch soon. The drug is also being developed to treat cancer. 

“We ask that if you're in industry or in government and you can support these clinical efforts, we beg you to help us move forward as rapidly as possible,” he said. 

Many large pharmas, on the other hand, have hauled in billions thanks to COVID vaccines and treatments, and yet few have offered up ideas to tackle long COVID. One major outlier is Pfizer, which is trying out its approved COVID treatment Paxlovid as a long COVID therapy, with two individual trials underway in conjunction with Stanford and Yale. The more recent Yale study was just cleared for enrollment, which a Pfizer spokesperson says will begin, “in the near term.”

Japanese Big Pharma Shionogi is similarly testing its COVID treatment, ensitrelvir, as a long COVID remedy. Exploratory data from the company’s phase 3 trial presented Tuesday found that 125 mg of ensitrelvir reduced the risk of long COVID by 45% compared to placebo.

The lack of funding noted by both Equels and Koziel is the byproduct of two separate but related trends: the first is a tightening private biotech market that’s been less willing to bet on risky projects. With so much heterogeneity among patients and few clear-cut biomarkers, trying to treat long COVID is, in fact, one of the riskier bets. 

The second issue is that federal attention on COVID-19 is winding down. The national public health emergency is set to end in May and while that won’t explicitly impact the FDA’s ability to issue emergency use authorizations, the agency has been more restrained in recent months. It’s become an often-used trope, but industry representatives at the Tuesday discussion underscored the need for the federal government to be as committed to treating long COVID as they were an acute infection. 

“There's a lot of wonderful individual efforts and we've heard about some today but not the really coordinated effort that I think we need to see,” said Christopher Austin, M.D., a CEO partner at Flagship Pioneering who joined the venture capital firm in 2021 after nine and a half years at the National Institutes of Health, including as director of the National Center for Advancing Translational Sciences. 

Still, the federal government is attempting to take the baton from patients who have become a leading force in the effort to galvanize research and resources. Recruitment is ongoing in large-scale observational studies of long COVID patients organized by the NIH, dubbed the RECOVER Initiative, with more than 15,000 adults, pregnant people and children enrolled so far. The goal is to deepen the understanding of long COVID’s biology, hopefully opening new doors for drug developers to find new treatments. 

The RECOVER Initiative is a bright spot for patients who feel like they’re being ignored and left behind as pandemic policies wane. Julie Gerberding, M.D., a former Merck executive and current CEO of the Foundation for the National Institutes of Health, said it's imperative that the collective focus of the medical and science communities does not wane. 

“I think we're all anxious that we've been too quick to try and put COVID in the rearview mirror, and we have to take care that long COVID doesn't end up in that place,” she said.