New “Long Covid” Treatment Looks to Improve Patient Feeling and Function

Two years into the COVID-19 pandemic, there are still persistent misconceptions about the disease. Many still believe only certain vulnerable populations experience severe or fatal infection, or that symptoms are unlikely and short-lived.

However, 20-30% of people who contract COVID-19 experience post-acute sequelae, often called “long covid.” The most common symptom of long covid is fatigue, which can be so debilitating that afflicted persons are inhibited from going about day-to-day activities like working a job.

Axcella Therapeutics is currently in phase 2a of a clinical trial for AXA1125, their oral product candidate for long covid. Margaret Koziel, MD, the chief medical officer at Axcella, discussed what long covid is, who is at risk, and how Axcella is testing whether their therapy improves “feeling and function” among people with long covid.

Axcella is using endogenous metabolic modulators (EMM) to treat long covid and other difficult diseases that implicate multiple biological pathways. EMMs are substances produced by the body, which Koziel says is important because “We have an implicit promise, we believe, that these therapies will be safe and effective.”

Those who are most at-risk for severe COVID-19 disease are also the most likely to experience long covid, Koziel said. However, even a fully vaccinated individual with a mild breakthrough infection can have long covid.

Koziel explained that the SARS-CoV-2 virus hijacks the mitochondria, “the powerhouse of the cell,” to use for its own replication. Many viruses take advantage of the mitochondria, but Koziel says that COVID-19 is unique. “What’s interesting about this virus is how often it does this, and how it persists.”

Fatigue, the most frequently reported symptom of long covid, is a common indicator of mitochondrial disfunction. Koziel said that Axcella’s amino acid composition can restore mitochondrial function.

The AXA1125 phase 2 study uses the phosphocreatine recovery (PCr) time to gauge the “battery life” of the cell. The shorter the recovery time, the healthier the mitochondria. “The individuals who we’re studying with long covid in this trial have a PCr time at baseline of 50 seconds, which is like an aged individual, that’s what you might see if you do this test in an 80-year-old.”

The trial measures PCr time by the ability to walk farther in a 5-minute walk, which Koziel says speaks to “an improvement in both function and how people feel.”

“As a physician, what gets me out of bed every day and keeps me working…is this promise of bringing safe and effective therapies to patients,” Koziel said.