Mark Revord will never know for sure whether an experimental drug, known at the time as CM4620-IE, saved him from having a breathing tube inserted down his throat to manage his COVID-19 symptoms.
But the 59-year-old cyclist from Minneapolis took the drug as part of a small, early clinical trial after starting on low-flow oxygen in the hospital through a tube under his nose. He left Regions Hospital in St. Paul four days after starting the intravenous drug, never needing a ventilator or the breathing tube it requires.
“No one knows 100% for sure whether it worked or it didn’t,” Revord said in a recent interview. “My condition improved, and the [clinical trial] sure as heck didn’t hurt me. In my heart, I believe it helped me.”
Other patients in the 26-person study in Minnesota and Detroit also saw significantly reduced ventilator use and hospital stays, compared with a control group. The early positive outcomes were so strong that the Food and Drug Administration urged the drug’s maker, California-based CalciMedica, to convert the early experiment into a large-scale clinical trial.
That will begin as soon as August and may support an application for commercial approval for a new COVID-19 therapy.
The drug now carries the name Auxora, and COVID-19 patients receiving low-flow oxygen therapy for COVID-19 at HealthPartners’ Regions and Methodist hospitals in the Twin Cities may be eligible to enroll in the randomized, blinded experiment to test the drug’s effectiveness. The trial will enroll up to 400 people nationally with COVID-19 who are getting low-flow oxygen through a nasal cannula.
As has happened with other therapies potentially useful for COVID-19, the drug’s maker is issuing positive news releases and announcing new private fundraising while publishing scant clinical details, all while working closely with the FDA.
A May 28 news release from CalciMedica offered two datapoints from an interim analysis. Treated patients had more than a 50% reduction in the proportion who went on ventilators as compared with patients getting standard of care without the drug, the company said, and the length of stay for treated patients was “more than 50% shorter” than for the control patients.
Unstated were statistical parameters such as the confidence intervals for the top-line results and clinical details such as how many days of hospitalization the treated patients avoided and how many people in either group had adverse events.
“The full explanation of the data will be published in a peer-reviewed journal. For now, CalciMedica is just reporting top line data as described in the press release,” CalciMedica spokeswoman Karen O’Shea said via e-mail.
Dr. Charles Bruen, a critical-care doctor and the study’s principal investigator at Regions Hospital, said the drug was initially developed to treat acute pancreatitis, a painful and potentially deadly inflammation of the pancreas often caused by gallstone obstructions.
People with acute pancreatitis are prone to developing acute respiratory distress syndrome, or ARDS. So are those with serious cases of COVID-19. Most COVID-19 patients who end up on mechanical breathing machine appear to have ARDS, according to the peer-reviewed medical source UpToDate. Respiratory failure is a leading cause of death in COVID-19 patients.
During a clinical trial of the drug for acute pancreatitis, “patients we treated with this medication had less ARDS than those that weren’t on it,” Bruen said. “That was a purely accidental finding during that study. So when COVID-19 came around, and we were fishing for any hope, it was like, well, this may be one way to attack the hyper-inflammatory syndrome that the SARS-CoV-2 virus induces in patients.”
The upcoming trial for Auxora in patients receiving low-flow oxygen will be randomized and blinded, meaning patients will not know whether they got the drug. The trial is slated to start in August or September, and it is expected to be complete in the first quarter of 2021.
Although the clinical goals haven’t been defined yet, CalciMedica believes it will be important to focus on changes to time to recovery and the need for mechanical ventilation in patients who get the drug.