Why drugs? While there is palpable excitement over the great success of several vaccines against the CoV-2 virus, companies around the world also have been developing new anti-coronavirus drugs to treat infections. As of March 5, the Milken Institute tracker reports that 251 vaccines are still in development, and 323 anti-viral drugs also remain under development.
While vaccines have dominated our thoughts in recent weeks, drugs can still play a very important role too. For example, even though we have vaccines for influenza, we also have the drug Tamiflu that shortens and reduces the severity of the flu. The drug is useful when we guess wrong about the strains of flu to vaccinate against each year. It also is used as prophylaxis for people working with the flu virus in clinical and research labs since they often work with flu strains that are not included in the annual vaccines. Also, while we have not been able to develop vaccines against hepatitis C or HIV, due to the quirkiness of those viruses, we have been able to take advantage of their biochemical quirks to develop drugs that now cure hepatitis C and that have turned HIV into a manageable and mild chronic problem rather than a death sentence.
All of this begs two questions; why would vaccines be needed if we had an effective drug against the virus, and why would a drug be needed if we had an effective vaccine against the virus? The answer has to do with the difference between prevention vs treatment. Prevention (i.e., vaccination) is ideal, but it takes time to develop vaccines to novel pathogens; hence, the value of an effective anti-coronavirus drug to treat novel species of the virus that will arise in the future. Treatment (i.e, with a drug) also is good, but it still is better to prevent disease than to respond to it after you get sick.
So, there definitely remains a significant role for an effective anti-coronavirus drug even while we have successful vaccines. First, some people cannot be vaccinated or they have a compromised immune system that would render a vaccine ineffective. These people need an effective anti-viral drug. Second, as we have seen over the last decade with SARS, MERS, and now CoV-2 and its variants, deadly coronaviruses are popping up that require a swift response by public health folks. Even though the vaccines to CoV-2 were developed in record time, the virus still killed a couple million people around the world and caused untold long-term health problems in millions more before we had the vaccines. Furthermore, the current vaccines very likely will not be effective against the next species of coronavirus that visits us. Current vaccines also might show reduced effectiveness against newly arising CoV-2 variants. In fact, the AstraZeneca vaccine has proven so ineffective against a novel CoV-2 strain that arose in South Africa, that that country no longer uses it. Therefore, having a drug that can be quickly distributed to meet a new coronavirus threat would go a long way to protect us against future outbreaks while vaccines are being developed.
The new anti-viral drugs: More than a year into the pandemic, we have very limited drug options. Hydroxychloroquine showed early promise, but controlled clinical trials showed it to be a bust, as was ivermectin, which the FDA recently disapproved for COVID-19 patients. Only remdesivir has been authorized for use in COVID-19 patients, and it only provides modest benefit in hospitalized patients, reducing their stays by a couple of days. However, recent encouraging, but preliminary, results suggest an effective anti-coronavirus drug might have been found. The pill, molnupiravir, which is being developed by Ridgeback Biotherapeutics and Merck, significantly reduced infectious virus in 182 subjects in a phase 2 clinical trial. After five days of treatment, no virus was detected in any of the treated volunteers, while subjects who received a placebo did show virus. The drug interferes with the biochemistry involved in viral reproduction inside cells, therefore it prevents viral spread. Further study of the new drug is under way.
And four other potential anti-viral drugs are in mid-to-late stage trials at NIH under the Accelerating COVID-19 Therapeutic Interventions and Vaccines (ACTIV) program. ACTIV is a public-private partnership program to coordinate research strategy that prioritizes and speeds development of promising COVID-19 treatments and vaccines, and was launched on August 4, 2020. Like the vaccines, these new antiviral drugs are being developed in record time.
The drugs include SNG001 developed by Synairgen; it is an inhalable beta interferon delivered by nebulizer. Beta interferon is a cytokine produced by virally infected cells as a first line defense against viral replication. There also is AZD7442, a long-acting monoclonal antibody combination (AstraZeneca), and Camostat mesilate, an orally administered enzyme inhibitor designed to block CoV-2 from entering cells (Sagent Pharmaceuticals).
Eli Lilly has also reported positive results with a combination of two antibody drugs, bamlanivimab and etesevimab (who comes up with these names?), that cut COVID-19 hospitalizations and deaths by 70% in recently diagnosed patients. These are anti-CoV-2 antibodies produced in the laboratory and work by mimicking the body’s immune system to give infected patients a head start fighting the disease while their natural immune systems ramp up to deal with a new pathogen. These also were developed as part of the ACTIV program and have been approved by the FDA to treat mild to moderate COVID-19 in people at high risk for severe disease. The feds have purchased large quantities of these Lilly antibody drugs and is making them available to qualified patients at no cost. Meanwhile, on January 5, 2021 Durham, NC biotech company, Brii Biosciences, launched an ACTIV study on two other investigational lab-produced antibodies designed to neutralize the CoV-2 virus
That leaves a bit over 300 more investigational anti-coronavirus drugs to go.