By Pamela Divack, Consultant , Life Sciences Research

With omicron spreading rapidly throughout the U.S.—even among the vaccinated—there's been one question I keep thinking about: what's the status of Covid-19 treatments?

There are more than 300 Covid-19 therapeutics in development. These treatments could play a critical role in preventing hospitalization and death from Covid-19, curbing the ongoing severity of the pandemic. But among the hundreds of treatments, which ones will actually contribute to the fight against Covid-19? And what will it take for them to succeed?

To help narrow in on an answer, I think it's critical to step back and determine where we stand—while unpacking the key questions that will determine future success.

'Game changer' oral antivirals are almost here.   

Antiviral drugs work by inhibiting the enzymes that viruses need to replicate in human cells. We've seen major progress recently on two oral antiviral drugs—one combination antiviral from Pfizer, and one antiviral treatment from Merck and Ridgeback Biotherapeutics.

New data about Pfizer's oral antiviral, Paxlovid, showed that the drug can reduce the risk of hospitalization and death in high-risk adults with Covid-19 by 89 percent—which led Pfizer CEO Albert Bourla to deem the drug as "a real game-changer in the global efforts to halt the devastation of this pandemic." An interim analysis of another study showed the drug led to a 70 percent reduction in hospitalization and no deaths in standard risk adults. The company said its drug likely works against omicron, and FDA could authorize the drug within days. In preparation, the Biden administration has ordered enough to treat 10 million people.

Merck's oral antiviral, molnupiravir was shown to reduce the likelihood of hospitalization by 30%—a drop from the estimated 50% earlier this year. Last month, an FDA advisory committee voted 13-10 in favor of authorizing the drug, citing concerns about its safety. FDA scientists identified potential toxicity to developing fetuses and the potential risk of viral mutation. An FDA decision could come any day now, and the Biden Administration has ordered enough to treat 3.1 million people.

I'm closely watching the oral antivirals, but let's not forget about other new and approved drugs.

The status (and projected future) of monoclonal antibodies

Monoclonal antibody treatments are created using antibodies that were naturally generated by either a human or animal infected with a specific pathogen, and the treatment relies on those antibodies to neutralize the virus. These treatments are typically administered by an infusion in a clinical setting.

Some antibody therapies have been authorized for months. However, several challenges have prevented widespread adoption—such as lack of infrastructure for identifying patients and getting them into the clinic for treatment, Covid-19 exposure concerns, and supply shortages. While these challenges will likely persist, the fate of antibody treatments will depend on whether they work against the omicron variant.

GlaxoSmithKline and Vir Biotechnology said their antibody treatment, sotrovimab, is likely effective against the omicron variant. This drug may prove critical in the coming weeks as we await oral antivirals, and HHS recommended preserving the treatment for the highest-risk individuals due to limited initial supply. Regeneron, however, announced that its treatment has lower potency against omicron. The company plans on conducting clinical trials in the first quarter of 2022, meaning new, more targeted treatments could be on the horizon.

To date, antibody treatments have been used to prevent disease progression. However, one new treatment to watch is AstraZeneca's Covid-19 antibody treatment, Evushield, the first preventative treatment for people with weakened immune systems. In August, AstraZeneca reported that Evusheld reduced the risk of symptomatic Covid-19 by 77% in a late-stage clinical trial of 5,197 participants, more than 75% of whom had comorbidities that could render vaccines less effective. It's unclear whether this works against omicron, but the company is "optimistic." This treatment may be critical for immunosuppressed people and protect those at highest risk during the pandemic's next wave.

What will determine success moving forward? Here's what I'm watching:

1. Will the treatments prove to be efficacious against omicron?

   As previously discussed, manufacturers believe that oral antivirals will be effective against omicron, although additional tests will be needed to confirm this. However, it's likely that the effectiveness of antibody therapies against omicron are of greater concern than antivirals, since they target the spike protein that the coronavirus uses to enter cells—and omicron has 30+ mutations to that region.

2. Who will be eligible to receive authorized treatments—and will providers follow recommended guidelines?

   Some treatments were studied in narrow patient populations. For example, Pfizer's Paxlovid was studied in unvaccinated people at high risk of severe Covid-19, within five days of symptoms onset. FDA will likely authorize the treatments for the population studied in the trials. But other Covid-19 patients may demand the treatment, raising difficult questions for doctors and insurers. We may see some patients start to "treatment hunt" and seek doctors willing to prescribe the treatments—similar to what we observed with "vaccine hunters" last year and the inequities surrounding it.
   
   For both oral antivirals and antibody treatments, limited supply is expected upon rollout. Health care leaders should prepare to address these requests and have prescribing protocols in place.

3. Will we have enough fast, accurate, and accessible tests to identify eligible patients—and will those tests be able to detect variants?

   The availability of rapid tests will play an important role in the success of oral antivirals, which must be administered shortly after symptoms begin. But since rapid tests are still difficult to access, more needs to be done to ensure equitable access. Health care facilities, employers, and frontline organizations may need more robust testing infrastructure across clinics, community popups, mobile sites, pharmacies, at home, and other accessible sites.
   
   If data shows that certain treatments are more or less effective against the omicron variant, we will need enhanced testing to understand what type of Covid-19 people have to get them the right treatment.

4. Can we collect robust and accurate data to inform treatment efficacy and appropriate use?

   We have limited understanding of how treatments work in patients of different age, demographics, race, ethnicity, pre-existing conditions, contraindications, and populations not represented in trials. Additional real-world data is needed to best allocate treatments, maximize their effectiveness, and ensure equitable use. And candidly, since data collection has been all over the place throughout the pandemic, health care leaders need to hone in their efforts on accurate and coordinated data collection.

5. Will we have adequate infrastructure to prescribe, distribute, and reimburse treatments?

   In addition to existing challenges with antibody treatments, new challenges will arise with antiviral treatments which require patients to have a positive test and a prescription. Whether pharmacists and PCPs will be able to easily prescribe these treatments—and be reimbursed—may play a critical role. Other questions include:

6. • Will doses be reserved for the highest-risk patients, or will they be made available on a first-come first-serve basis?
   • Will there be geographical preference for allocation? Will areas with the highest case or hospitalization rates receive supply first?
   • Will public and private insurers fully cover this treatment or demand cost-sharing—and will they restrict access based on vaccination status, pre-existing conditions, age, demographics, or other risk factors?
   
   
7. Can information be communicated clearly—and will historically hesitant patients actually take the treatments?

   With treatments on the horizon, patients may have new questions and concerns, especially when it comes to potential side effects and contraindications.
   
   Additionally, the patients who may benefit most from the drugs—the unvaccinated—might be the most hesitant to take them. Health care leaders should proactively have conversations with patients to overcome the polarization of treatments. They should also prepare for misinformation and be honest when a lack of information exists.

8. Will the health care ecosystem adequately support patients throughout the process?

9. For antibody treatments, patient navigation from diagnosis to clinic is an ongoing challenge. Oral antivirals require patients to take multiple pills per day for many days, which may create new challenges with medication adherence. Some may have side effects—Pfizer's antiviral may cause nausea and vomiting. It's likely that pharmacists and care team members will play a critical role in helping patients adhere to the full course of treatment and manage side effects.

Keeping health equity at the forefront will be essential to success

Manufacturers, providers, pharmacies, and community organizations must come together to address these open questions. If we aren't careful, these treatments could exacerbate disparities and health inequities. If demand for the drug significantly exceeds supply, adequate rapid testing infrastructure isn't in place, treatments aren't deployed to under-resourced areas, or relatively low-risk patients demand access, there's a risk that better-connected, highly-resourced patients or areas could benefit more than historically marginalized populations.

Parting thoughts

In the last few weeks, I've felt a bit of déjà vu. I think we are all sharing some collective anxiety. Where I live in New York City, cases are up 246% in the last 14 days. Lines for testing are multiple blocks long, test results are delayed, and, quite frankly, people are nervous about the uncertain status of our future. News of 800,000+ deaths due to Covid-19 struck us when we were down.

But amid the continued chaos of Covid-19, I think it's okay to pause and acknowledge the collective grief that many of us may be experiencing. The thought of "Shouldn't we be done with this by now?" crosses our minds from time to time. But despite these ongoing challenges, I don't think we're back to where we started—no matter how harsh the déjà vu may feel.

These Covid-19 treatments were completely absent when the pandemic began, and now we can actively narrow in on how they will play a critical role in protecting the most vulnerable and preventing more suffering and deaths. The more tools we have in our toolbox, the more hopeful I am that the worst may be behind us. So if you feel some anxiety about the current Covid-19 surge, think about how large our toolbox has grown over the past two years. We've come a long way. And if these treatments prove even a bit effective in reducing deaths and hospitalizations, that feels like success to me. We have a long way to go with ramping up our infrastructure to maximize the benefits of these treatments, and I'll be watching this closely. It is my hope that the new year brings even more fruitful developments and progress in the fight against Covid-19.