Most conversations about ending the Covid-19 pandemic have centered around vaccine development and deployment. While the Covid-19 vaccine rollout is undoubtedly essential to curbing the pandemic and achieving herd immunity, drugs and therapeutics—such as antibody therapies, antivirals, and others—will play a critical role in reducing the severity of Covid-19 for those infected and bridging the gap to herd immunity.
Toolkit: Covid-19 vaccine communications readiness assessment
According to the Covid-19 Treatment and Vaccine Tracker from the Milken Institute's FasterCures center, more than 300 Covid-19 therapeutics are currently in development. Read on to learn about the most promising treatment options and the open questions that will determine their success.
Antibody therapies continue to show efficacy—but access remains a problem
Several antibody therapies fall within a class of drugs already helping to treat patients with Covid-19. These biologics are created using antibodies that were naturally generated by either a human or animal infected with a specific pathogen, and those generated antibodies then function to fight off the virus. For Covid-19 antibody therapies, the treatments rely on isolated antibodies to neutralize the virus.
FDA has already authorized two antibody treatments for emergency use during the Covid-19 pandemic—Eli Lilly's combination treatment of bamlanivimab and etesevimab administered together, and Regeneron's combination treatment of casirivimab and imdevimab. Both treatments are infusion-based.
New clinical trials and real-world data indicate that the combination treatments are highly effective in reducing the severity of Covid-19 in infected people. Eli Lilly recently released data showing that their combination antibody treatment was 87% effective in preventing hospitalizations and deaths. Separately, new data from Regeneron showed that its antibody combination treatment reduced the risk of Covid-19 hospitalization or death by about 70% in a large clinical trial.
Government officials, manufacturers, and researchers are closely monitoring these treatments to understand whether they continue to work against emerging Covid-19 variants. Notably, FDA recently revoked an emergency use authorization (EUA) for Eli Lilly's previously authorized single antibody treatment, bamlanivamb, citing variants' resistance to the therapy. So far, data suggest that combination therapies may be more effective than the single antibody therapy in fighting both the original virus and newer variants—offering hope to those who may contract Covid-19 and for manufacturers with additional combination therapies in development.
And there are several additional promising antibody therapies in clinical development. For example, GlaxoSmithKline (GSK) and Vir Biotechnology announced that they are seeking an EUA for their antibody treatment after Phase III data showed that the drug reduced hospitalization or death by 85% compared to placebo. GSK and Vir's therapy might even be used in combination with Eli Lilly's bamlanivimab after new data demonstrated that their combination therapy reduced viral loads by 70% compared to placebo. In addition, Regeneron recently released new data showing a single under-the-skin injection of its monoclonal antibody reduced the risk of symptomatic infections in individuals by 81%. The company plans to submit the data to FDA to seek an EUA for the injection to be used as a preventative treatment.
However, providers have not yet fully utilized available antibody treatments. Although authorized therapies are most effective among newly diagnosed people, providers struggle to identify eligible patients and get them into infusion clinics early enough to reduce the risk of disease exacerbation. In addition, some provider sites struggle to identify space to set up infusion centers for Covid-19 patients and dedicate staff to proactively reach out to patients to let them know whether they can receive treatment. As a result, access and utilization remain limited today.
Antiviral drugs could offer a future 'Tamiflu-like' approach to treat Covid-19
Like antibody treatments, antiviral drugs can reduce viral loads, lessen the severity of Covid-19, and reduce hospitalizations and deaths. Antiviral drugs work by inhibiting the enzymes that viruses need to replicate in human cells. Gilead's remdesivir, which is sold as Veklury, is one prominent example of an antiviral drug currently approved or authorized to treat Covid-19.
However, there are many other antiviral drugs in clinical development that show promise, too. Merck recently released data from a Phase II trial showing that its anti-viral pill, molnupiravir, appears to be safe and effective in cutting down the time that patients test positive for Covid-19. Pfizer is also testing two antivirals. One is an oral antiviral given to patients as soon as they see signs of infection, and the other is an intravenously administered antiviral candidate in an early-stage trial for hospitalized Covid-19 patients.
But some antiviral drugs have one major advantage: Oral antiviral therapies may be inexpensive and easy to distribute across the country. Notably, researchers are currently calling oral antiviral therapies the "Tamiflu" of Covid-19, as people infected with Covid-19 may be able to take the antiviral treatment immediately after diagnosis to lessen the severity of the disease quickly.
Researchers turn to new and existing drugs for additional protection
Beyond the antibody and antiviral therapies, researchers continue to develop new drugs and repurpose existing compounds that may treat Covid-19—and many show early promise.
One emerging category of interest for new Covid-19 therapeutics is cell-based therapies. These therapies help patients' immune systems coordinate with other cells in the body to react to the infection and help patients heal. Currently, more than 30 cell-based therapies are under development to treat Covid-19, according to FasterCures' database.
Another well-publicized treatment category is convalescent plasma. However, current NIH guidelines do not recommend for or against the use of convalescent plasma to treat Covid-19, citing insufficient data.
Researchers are also testing whether authorized Covid-19 vaccines can help patients with long-haul Covid-19, and early anecdotal data indicates that the vaccine may offer symptom relief. However, robust research and data collection are required to fully understand vaccines' impact after an infection.
5 questions that will determine Covid-19 therapeutics' success
Expanded use and authorization of Covid-19 therapeutics can provide additional protection and support for people who get Covid-19. They can help build a bridge to herd immunity until most of the population is vaccinated.
As manufacturers and researchers continue to develop Covid-19 therapeutics, five questions will determine their success.
1. How well do the treatments work against variants? As therapeutics develop, researchers must continue to test their efficacy against emerging variants. Currently, there is little evidence to show how well existing therapeutics work against current variants (except in the case of Eli Lilly's single antibody drug.) However, the U.S. government has already ordered antibody treatment manufacturers Regeneron and Eli Lilly to establish a process for monitoring genomic databases for variants and then run tests to determine whether their antibody therapies work against the new variants. However, antiviral manufacturers, such as Merck, predict that their pills should work on all Covid-19 variants based on their mechanism of action. Nevertheless, additional testing will be required to determine the full efficacy of all treatments against known and emerging variants.
2. How will providers and other clinical guideline-generating groups (e.g. the NIH) revise Covid-19 guidelines to recommend for or against certain treatments? As FDA authorizes more drugs (and providers and patients have more treatment options), prescribers will turn to clinical guidelines for insight into how to best treat patients given all the available therapeutic options. Today, data on available and emerging therapeutics remains limited, and most guideline developers cite insufficient data as a barrier to making more official recommendations for Covid-19 treatments. For example, despite recent authorizations of antibody drugs, NIH currently doesn't recommend antibody therapies in its Covid-19 treatment guidelines.
Medical societies and provider groups will benefit greatly from additional real-world evidence that could shed light on efficacy in different populations, as this information could contribute to more rigorous guideline recommendations.
3. How will the government support treatment distribution and use? The U.S. government has already purchased millions of doses of currently authorized treatments—including nearly 1.5 million doses of bamlanivimab, Eli Lilly's single antibody treatment, and more than 1.5 million doses of Regeneron's antibody cocktail of casirivimab and imdevimab. Also, HHS recently committed $150 million to increase access to Covid-19 antibody treatments for patients in vulnerable communities. These efforts will likely increase the access and availability of therapeutics across the country.
4. How will providers optimize available and future therapeutics to treat patients? Providers must overcome barriers standing in the way of the rapid prescription and administration of antibody treatments in infusion settings. They must develop processes to identify Covid-19 patients eligible for treatment, conduct proactive outreach to get patients into clinics in time for the treatments to have an impact, and dedicate space and staff for running infusion clinic. However, with more efforts to increase the accessibility of therapeutics, such as HHS' funding, coupled with potential authorizations of easy-to-use oral antivirals, treatment availability may increase in the future.
5. How will cross-industry health care stakeholders educate the public about treatment availability? Even after vaccinations become widespread, providers, governments, researchers, and manufacturers must inform the public about currently available treatments, including when and how to seek them. They will also need to educate patients about potentially changing qualification criteria and information about sites of care.
As vaccinations become increasingly widespread, authorized Covid-19 treatments and additional drugs in development will continue to play a critical role in curbing the severity of the pandemic and reducing disease burden in those infected with Covid-19. Providers and other health care stakeholders must continue to monitor treatment development and identify opportunities to leverage existing treatments to treat patients.
