The First Pill for COVID-19 Treatment Could Be Ready by Year's End
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COVID-19 patients may be treated with new pills now in mid-stage clinical trials, which could be ready by the end of the year if successful.
For hospitalized COVID-19 patients, only Veklury, containing remdesivir, is the treatment the FDA (US Food and Drug Administration) has fully approved, and this drug is administered intravenously (into a vein).
Hopes of a day when we can rid COVID-19 patients' bodies of the virus with just a pill rose when early study results were presented at a medical conference.
Designed to do for COVID-19 patients what Oseltamivir (Tamiflu) can do for flu patients, the experimental oral COVID-19 drug molnupiravir had its interim phase 2 results presented at the 2021 Annual Meeting of the Conference on Retroviruses and Opportunistic Infections (CROI).
What Is Molnupiravir? Molnupiravir is an experimental antiviral drug activated when taken orally and was originally developed to treat influenza (flu). It is a prodrug of the synthetic nucleoside derivative N4-hydroxycytidine and exerts its antiviral effect by introducing copying errors during viral RNA replication.
In the small clinical trial testing molnupiravir, the pill significantly reduced infectious virus in symptomatic patients who, within the previous 4 days, had a COVID-19 test that was positive but had not been hospitalized.
After 5 days of treatment, no participant receiving molnupiravir had detectable virus, whereas it was detected in placebo recipients at a rate of 24%.
Other Trials
RedHill Biopharma is developing two other oral agents: one for severe COVID-19 infection in hospitalized patients and another for mild infection in patients at home.
The first, opaganib (Yeliva), entered global phase 2/3 trials for hospitalized patients after the company released top-line safety and efficacy data in December. In phase 2, the drug was shown in oxygen-requiring serious COVID-19 patients to be safe and to effectively reduce oxygen requirements by the end of treatment.
RedHill chief operating officer Gilead Raday told Medscape Medical News that the drug's combination of antiviral and anti-inflammatory effects was an important feature. Data on its performance in 464 patients are expected midyear. It is being tested on top of remdesivir or in addition to dexamethasone.
The second, upamostat (code name RHB-107), is currently undergoing phase 2/3 trials in the US and is being investigated for use in non-hospitalized COVID-19 patients.
Raday said, "I expect the data to be ready in the second half of this year."
According to the company, upamostat is a novel serine protease inhibitor expected to work against emerging variants because it targets human cellular factors involved in viral entry.
Other drugs are being investigated in earlier-stage studies.
The Urgent Need for Oral Drugs for COVID-19
Infectious disease experts are enthusiastically watching progress toward a COVID-19 pill.
Dr. Sarah Doernberg, an infectious disease specialist at the University of California, San Francisco, said, "We desperately need an oral treatment option for COVID."
She told Medscape Medical News, "There is a real gap in our arsenal against COVID-19 for outpatient care, which is actually where most people who get COVID-19 will seek care."
She explained that although some studies have shown benefits of monoclonal antibodies for prevention and early treatment, there are significant logistical problems because all available options require IV (intravenous) administration.
"If we had a pill to treat early COVID, especially in high-risk patients, it would fill a major gap." she said, noting that a pill could help people recover faster and avoid hospitalization.
According to Doernberg, molnupiravir studies show reduced viral transmission in the first few days after COVID infection.
There is great excitement about the drug, but it will be important to see whether the findings translate into fewer people needing hospitalization and people feeling better sooner.
Doernberg said, "I want to see the clinical data."
She will also watch the upamostat and opaganib results in the coming months.
“If these drugs are successful, I think we might be able to use them this year, perhaps under emergency use authorization. When an antiviral pill becomes a viable option for COVID-19 treatment, questions about its use will arise,” she said.
One question is whether patients receiving remdesivir in hospital who are ready for discharge after 5 days should continue treatment with antiviral pills at home.
Another question is whether the pills, if proved effective, might help after COVID exposure. This use would be important for people who do not have COVID-19 but are in close contact with someone they live with who has tested positive.
Doernberg said, "We have this model. In flu, for example, we know that oseltamivir can be used for post-exposure prophylaxis and help prevent clinical illness from developing."
She warned, however, that one problem with COVID is that people become infectious very early. A pill needs the ability to test for COVID-19 early and connect patients to care immediately.
"These are not trivial challenges." she said.
Can Vaccines Alone End the COVID Threat?
Doernberg said treatments are part of a “belt-and-braces” protective approach alongside vaccines in tackling COVID-19.
“With vaccines, we will not completely eliminate COVID. We will still need treatments for people who do not respond to a vaccine, have not been vaccinated or develop disease despite vaccination." she said.
Kenneth Johnson, a professor of molecular biosciences at the University of Texas in Austin, agreed that oral formulations were desperately needed.
Currently, remdesivir treatment involves patients being connected to an IV (intravenous line) for 30 to 120 minutes daily over 5 days. A 5-day course of remdesivir costs between 2340 and 3120 dollars in the United States.
"We hope we can find something a little easier to administer that we can use without much concern about toxic side effects." he said.
Johnson's team at UT-Austin recently made an important discovery about how remdesivir stops viral RNA from being copied.
Understanding where the virus begins to multiply in the chain of infection and how and where it reacts with remdesivir may lead to better, more concentrated antiviral pill formulations with less toxicity in the future.
The team used a laboratory cell culture dish to recreate, step by step, the process that occurs when a patient infected with SARS-CoV-2 receives remdesivir.
Johnson explained that the discovery would not lead to an effective COVID-19 pill for our current crisis, but would be important for the next generation of drugs needed to handle future coronaviruses.
He emphasized that there would be other coronaviruses and that this was the third coronavirus to jump from animals to humans in 20 years. "It is only a matter of time." he said.
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