More than a dozen drug firms in Massachusetts are urgently searching for a medicine to treat COVID-19, but the most potent therapy may not end up being a single medication. Instead, medical experts say, the most effective way to battle the disease will likely be a combination of drugs taken together.
Two weeks after the federal government allowed hospitalized coronavirus patients to receive an experimental drug that provided only modest benefits, scientists say it increasingly appears the best treatment will be a cocktail of medicines similar to those used for other deadly infectious diseases, from tuberculosis to AIDS.
The need to develop drugs that can dramatically lessen symptoms of COVID-19 is especially crucial because a vaccine that could prevent the disease likely remains a year or more away.
Dr. Barry Bloom, a professor at the Harvard T.H. Chan School of Public Health, said he’s optimistic that one or more medicines better than remdesivir — the experimental Gilead Sciences drug cleared for “emergency use" on May 1 ― will be available by the year’s end. But he expects the standard of care will probably evolve and ultimately rely on a combination of drugs that pass muster in clinical trials.
“You don’t need only one drug,” said Bloom, a pioneer in global health who devoted much of his career to treating tuberculosis. “What we learned with HIV is that no one drug works very well. But if you put three drugs together that are pretty good drugs, you can control the virus for life.”
Bloom and other experts suspect that unlike people with HIV, COVID-19 patients would require only short-term treatment with a combination of medicines and recover faster if they got them soon after symptoms appear.
A study published last Friday in Lancet, the respected medical journal, bolsters that notion. It found that patients with mild to moderate COVID-19 at six public hospitals in Hong Kong and the University of Hong Kong seemed to improve more quickly if treated with a three-drug combo, compared with a group that received a two-drug treatment. The triple combination featured three antiviral drugs: one used for HIV, another for hepatitis C, and a third for multiple sclerosis.
The federal website ClinicalTrials.gov lists more than 1,400 clinical trials related to COVID-19 planned or started around the world. A number of them involve combinations of approved and experimental drugs, including remdesivir.
Massachusetts General Hospital, which participated in the global trial of 1,063 coronavirus patients that led to the emergency use of remdesivir, plans to participate in a follow-up study that combines that antiviral medicine with another drug. That second drug is sold under the brand name Olumiant by Eli Lilly and is used to treat rheumatoid arthritis.
Dr. Libby Hohmann, principal investigator of the remdesivir trial at Mass. General, said the Gilead drug “had a real statistically significant effect, but as a lot of people are saying, it’s not a magic bullet or home run.” That’s why it makes sense to try to combine it with something else, she said.
Patients who received remdesivir had a 31 percent faster recovery than those who got a placebo, according to the National Institute of Allergy and Infectious Diseases, which ran the trial at 68 sites worldwide. The median recovery time was 11 days for patients who received remdesivir compared with 15 days for those who got a placebo.
Most researchers predict it will take a vaccine to end the pandemic and don’t expect one to be approved and deployed for 12 to 18 months, in the most optimistic scenario. As a result, researchers around the world are studying more than 200 experimental treatments to help sick patients recover, according to a tracker by the Milken Institute, a Santa Monica, Calif.-based think tank.
At least 15 drug companies based in Massachusetts or with an outpost in the state are studying possible treatments, as are local academic laboratories.
The firms include the Japanese drug giant Takeda Pharmaceutical, which is working with multiple partners on a drug made from the plasma of people who recovered from disease; Cambridge-based Alnylam Pharmaceuticals, which is collaborating with a San Francisco biotech on technology to silence the genes in the virus that causes COVID-19; and Sarepta Therapeutics, a Cambridge biotech collaborating with the Defense Department on an RNA-based treatment.
Akshay Vaishnaw, who heads research and development at Alnylam, said his company and Vir Biotechnology hope to begin testing an inhaled medicine in humans around the end of the year. The partners will first see how the drug performs by itself, he said, but it would hardly be surprising if researchers ended up studying it as part of a combination treatment.
“Combinations allow multiple lines of attack on the pathogen,” Vaishnaw said.
Ultimately, researchers say, the standard of care may encompass a cocktail of antiviral drugs that use multiple targets, or it may be several different types of medicines, such as antiviral medicines and anti-inflammatory therapies.
"Infections between a virus and a host cell are complicated processes that involve many different steps,” said Dr. Joseph Loscalzo, head of the department of medicine at Brigham and Women’s Hospital. “That, coupled with the fact that these viruses can mutate quickly, would argue that combinations would help optimize the chance for a cure.”
Loscalzo coauthored a recent study that ranked more than 80 approved drugs for their potential to work against COVID-19. The researchers used artificial intelligence and other tools to screen over 7,000 medications now used to treat other conditions.
The National Emerging Infectious Diseases Laboratories at Boston University is testing the roughly 80 drugs on cells from monkeys and humans infected with the coronavirus, and scientists there expect to have results soon.
Although combining drugs holds promise, it can also pose risks, Loscalzo said.
“Now you have to look at not just the toxicities of each drug, but the drugs when used in combination,” he said. “The [clinical] trial duration would likely be about the same, but getting to the point where you could, in a safe way, begin the trial requires more homework beforehand.”
Some scientists say they would prefer to repurpose a medicine that has been approved by the Food and Drug Administration for another disease rather than develop a new drug and test it in clinical trials, which can take years.
With all the drugs being studied, said Bloom, the public health expert from Harvard, it’s likely that data will emerge in the next couple of months about medicines that are better than remdesivir. But, he said, it’s premature to bet on any single drug or mix.
Like combination drugs marketed for HIV, he added, an effective cocktail might also become a medicine that doctors could prescribe as a preventative to patients who are at high risk for catching COVID-19. Gilead, which makes remdesivir, sells such a “pre-exposure prophylaxis," or PrEP, to prevent HIV. The product, marketed as Truvada, combines two medications.
“A drug that you could give to healthy people who would be exposed ― that would be a new and appealing preventative therapy," Bloom said.
Jonathan Saltzman can be reached at firstname.lastname@example.org.