Commentary Suggests That Remdesivir Should Only Be the Beginning

To use a horse-racing metaphor, when it comes to potential COVID-19 treatments, remdesivir remains the favorite into—hopefully—the final turn.

However, although the antiviral originally developed to treat Ebola virus has progressed farther along in clinical trials compared to other drug candidates—and, so far, produced positive results—our collective research efforts shouldn’t begin and end with the promising product. That’s the “take-home” message of a commentary published July 31 in Clinical Infectious Diseases.

“We need to consider multiple dimensions of COVID-19—stage/severity, goals of treatment, and the intervention—to develop effective therapies,” the author of the commentary, Rajesh Tim Gandhi, MD, told Contagion®.

“Depending on the stage and severity of disease, the optimal intervention may differ,” said Dr. Gandhi, an infectious disease specialist and professor at Harvard Medical School, who has been involved in several clinical trials for potential HIV/AIDS therapies. “Early in infection, antiviral therapies may be particularly important. These treatments may be small molecules that target the viral lifecycle, direct-acting antivirals like remdesivir, or antibodies against SARS-CoV-2, such as those found in convalescent plasma or monoclonal antibodies. Later in infection, anti-inflammatory medications—like dexamethasone—may be more impactful, particularly if disease is being driven by an over-exuberant immune response and excess inflammation.”

As Gandhi notes in his commentary, COVID-19 is a “multisystem disease” with neurologic, cardiac, renal, gastrointestinal, and cutaneous complications, some of which appear to be related to thromboinflammation. Treatments, therefore, should be tailored accordingly.

As an example, the author points to the promising results in the RECOVERY trial for the steroid dexamethasone, which has improved outcomes in patients hospitalized with severe COVID-19.

The HIV/AIDS researcher also issues a word of caution with regard to the “rush” to try unproven therapies for COVID-19, which he describes as “eerily reminiscent” of the pressure to administer and grant regulatory approval to drugs with “uncertain benefit” in the early days of HIV. Although he acknowledges that the urge to provide patients with some home is a “natural impulse,” it should go without saying that it “must be tempered by the importance of finding out whether a medication does or does not work.”

“We can learn from our experience with HIV in developing treatments for COVID-19, and the comparative trials that established the role of remdesivir and dexamethasone in the treatment of COVID-19 are excellent examples of the progress that can, and will, be made if we are guided by the science,” Gandhi told Contagion®. “[However], incremental progress is necessary to eventually making transformative advances in the care of a disease. With HIV, it was the development of antiretroviral medications that, when combined, led to long-term control of a previously fatal infection. With COVID-19, remdesivir is not the be-all and end-all of therapy; rather it is a foot in the door, a first step towards what will hopefully be a tipping point.

“I think remdesivir is an important first step but clearly much more needs to be done,” he added. “Because remdesivir is an intravenous medication, it is useful in hospitalized patients, but we need more convenient—ideally oral—therapies for outpatients who comprise the majority of people with COVID-19.”