A Deep Dive Into COVID Oral Treatments — What Does the Atea Failure Mean for Oral Antivirals?

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The following post was written and/or published as a collaboration between Benzinga’s in-house sponsored content team and a financial partner of Benzinga.

Some big news circulating was of Atea Pharmaceuticals’ AVIR COVID-19 antiviral clinical trial failure, which instantly plummeted the stock by about 65%. AT-527, the company’s COVID-19 oral antiviral, was considered by many to be its lead asset.

This could be a wake-up call for the industry that viral inhibitors ultimately work in the viral stage of the disease, not the inflammatory stage. There is one notable exception: Todos Medical TOMDF is one of the final, late-stage, oral antivirals. Phase 2 interim results should be announced by Nov. 30 before Merck & Co. Inc.’s MRK Adcom meeting for molnupiravir.

Oral Antivirals Take Center Stage

Vaccine makers slumped after Merck announced its oral antiviral was able to reduce hospitalizations by 50% and reduce deaths by 100%. Molnupiravir, Merck’s drug, was administered to people with mild-to-moderate COVID-19 with little risk of going into the hospital within the next few days. At the time of the interim analysis, only 377 evaluable patients had taken the drug yet Merck’s stock soared $15 billion dollars in market capitalization. 

The company is seeking an Emergency Use Authorization (EUA) from the Food and Drug Administration (FDA) for molnupiravir, but there are drugs like CytoDyn’s CYDY leronlimab, which had an 82% reduction in mortality in a cohort of critically ill patients. The company was asked for more data even though it had 265 evaluable patients versus Merck’s 377. 

Molnupiravir works by promoting mutations, inhibiting the same biological target as does remdesivir. This means there can be a risk of cancer or birth defects as well as the promotion of viral variants in those patients who can’t snuff out the virus. 

COVID-19 Antiviral Commercial Hurdles 

The initial promise of Regneron Pharmaceuticals Inc.  REGN and Eli Lilly and Co.’s LLY monoclonal antibodies gave way to supply and logistical challenges to safely infuse people. The crux of the problem was quickly identifying the right patient population in time for the treatment to make a difference. Should molnupiravir or any other oral antiviral like Pfizer Inc.’s PFE PF-07321332 receive approval, it may still be a challenge to identify patients within 5 days of symptom onset. 

The rapid antigen tests are best used 9 to 14 days after exposure. According to MIT Medical, delta patients on average are symptomatic in 3 to 5 days with peak viral load at 3.71 days. This can be a tricky situation if patients are symptomatic in 4 days.

Are the Remaining Contenders Adamis Pharmaceuticals and Todos Medical?

There are two antivirals in development with a dual anti-inflammatory and antiviral mechanism of action. The first is Adamis Pharmaceuticals Corp.’s ADMP Tempol, which is being tested in a phase ⅔ trial in moderate patients. Adamis is enrolling unvaccinated patients only, which might be a commercial roadblock but could help the company obtain better clinical results. Tempol interferes with the same target as Gilead Sciences Inc.’s GILD remdesivir and molnupiravir as well as Appili Therapeutics’ APLIF favipiravir but through a different mechanism that should make it theoretically safer.

Todos Medical TOMDF has an antiviral drug called Tollovir, which is expected to release phase 2 interim data within 6 weeks. The active ingredient has already been safely given to more than 5,000 people. Todos released data a few weeks ago in hospitalized patients in the thick of the cytokine storm phase of the disease. 

The inflammatory C-reactive protein (CRP) serum levels demonstrated that patients were severely ill compared with nonhospitalized patients being recruited in the Tempol study. Tollovir reduced hospitalization days, death (by 100%) and inflammatory biomarkers (CRP) compared to untreated patients. No exclusions were made for pregnancy, underlying conditions, or vaccination status, so the efficacy looks consistent across a wider population. This drug blocks the same target as Pfizer's antiviral candidate.

The most successful antivirals may be the ones that can be given to and actually help virtually any patient without any side effects. Additionally, the remaining treatments could be uniquely promising as they have dual mechanisms of action as antivirals and immune modulators. 

The preceding post was written and/or published as a collaboration between Benzinga’s in-house sponsored content team and a financial partner of Benzinga. Although the piece is not and should not be construed as editorial content, the sponsored content team works to ensure that any and all information contained within is true and accurate to the best of their knowledge and research. This content is for informational purposes only and not intended to be investing advice.