What do you know about the new Covid antiviral pills from Merck and Pfizer?
FIRST ORAL TREATMENT
Molnupiravir, developed by the US drug companies Merck, Sharp and Dohme (MSD) and Ridgeback Biotherapeutics,is the first antiviral medication for Covid-19 which can be taken as a pill rather than injected or given intravenously. The first results from Merck and Ridgeback Therapeutics, were released in October and will be considered and looked over by an advisory panel to the Food and Drug Administration in December. That could lead to an emergency use authorization in the U.S. by the end of the year. In clinical trials the pill, originally developed to treat flu and prevent the risk of hospitalisation or death by about half.
Some of the important facts about the Molnupiravir pill are as follows:
- Molnupiravir pill, reduced hospitalizations by 50% and prevented deaths entirely when it was given within five days of when symptoms began.
- The pill is given as a five-day course during which patients take a total of 40 pills.
- Molnupiravir pill will be given twice a day to those patientswho have been recently diagnosed with the disease.
In November, Pfizer announced that its Covid pill, Paxlovid, reduced hospitalizations by 89% and also prevented deaths in vulnerable adults, as the clinical trial results suggested. It comes a day after UK medicine regulator approved a similar treatment from Merck Sharp and others. Pfizer firm says that it stopped trails early as the initial results were so positive.
Some of the important facts about the Paxlovid pill are as follows:
- Paxlovid pill is intended for use soon after symptoms develop in people at high risk of severe disease.
- As with the Merck drug, Paxlovid is given as a five-daycourse.
- It must also be given with a second medicine, which is a booster, called ritonavir, which is made by AbbVie, another large drug firm.
- The Pfizer procedure involves taking 30 pills over a five-day period.
Though the results are similar of both the pills, the medicines could have different risks and benefits. As there is a lot of data available and disseminated by the companies, but it is only published in press releases and not scientific articles. Also, the doctors need to know and gain a lot more knowledge of both the pills.
Here is an overview of what we still don’t know about the Covid pills (Molnupiravir & Paxlovid) and we might learn about it.
WHICH ONE WORKS BETTER?
As we see at the headline level, Pfizer’s pill reduced the risk of hospitalization and death by 89% while Merck showed a reduction of 50%. But neither firm has disclosed complete data from its pivotal studies, and the clinical trials were not identically designed.
The studies enrolled similar populations in which both included unvaccinated people who had mild to moderate Covid-19 and at least one risk factor for severe disease but they had slightly different measures of efficacy. Pfizer’s 89% figure comes from those patients who started getting their pill, Paxlovid, within three days of their first Covid-19 symptoms. In the Paxlovid study, patients who started their overall treatment within five days saw an 85% improvement in hospitalization or death versus placebo.
Merck’s 50% reduction figure applies to those patients who began their treatment within five days after their first Covid-19 symptoms. But Merck has not shared data on patients who got its pill within three days of symptom onset. But what came to notice, both the studies had in common was 100% efficacy against death regardless of when patients started their treatment. Merck’s study counted and specified eight deaths among patients on placebo, and Pfizer’s observed 10.
The rate of side effects in both studies was similar between the treatment groups and placebo groups but neither firm has disclosed detailed data on the type and severity of side effects.
WOULD THEY WORK BETTER IN COMBINATION? AND WOULD THE FIRMS ALLOW THAT TO HAPPEN?
Theoretically yes, but it’s unlikely to happen. Combinations of antiviral drugs are the standard treatment for people with HIV/AIDS because it reduces the risk of resistance caused by mutations in the virus. Since the Pfizer and Merck pills attack Covid-19 differently, using them in combination might offer the same protective benefit for patients with Covid-19.
But the main challenge is that since these drugs are developed by different companies, neither Merck nor Pfizer are motivated to run a combination therapy trial. However, the National Institutes of Health or other institutes could do that because it’s really important that they start to develop a combination therapy.
Mikael Dolsten who is the firm’s head of research and development argued in an interview that Pfizer’s antiviral is potent enough to protect against new strains and already has strong efficacy. So combining the drugs or pills would only add the potential for more risky side effects.
WILL THE ANTIVIRAL BE AVAILABLE FOR VACCINATED PEOPLE WITH BREAKTHROUGH INFECTIONS?
Both the firms conducted their studies with patients who were at high risk of complications if they get Covid-19 and who also have not been vaccinated. This leads to a big question for policymakers. Should those people who have been vaccinated, but who develop a breakthrough infection of Covid-19, be given the pills?
A third antiviral pill, from the biotech firm Atea and the large drug firm Roche, failed to prove it was effective in its own study. So, the Wall Street analysts investigated and then suspected the reason is that the firms included vaccinated patients in the research. For those who have received the vaccine, hospitalization and death are much less likely. This means that it is harder for a drug to show efficacy because there are fewer infections to prevent.
So, regulators and public health officials will have to make a judgement on the risks and benefits of the Covid pills for people with breakthrough infections without direct data in these populations.
Pfizer is running a clinical trial, with results due next year, that does include vaccinated patients, and the firm’s executives have expressed confidence based on the results so far that the treatment should work. Both Merck and Pfizer are also running studies to show that the drugs can prevent people from developing symptoms if they take the antivirals after they are exposed to the virus.
DO THE DRUGS WORK THE SAME WAY?
No, not really. While both drugs interfere with the process the coronavirus uses to reproduce itself, each drug interferes at a very different point.
After someone takes molnupiravir, the drug is transformed into something that is unsettling similar to one of RNA’s chemical building blocks. Ultimately, this leads to what’s known as error catastrophe. It’s introducing so many different mutations that, eventually, nothing further can happen”.
Pfizer’s drug, Paxlovid, acts at a completely different point in the virus’ reproductive process. Unlike molnupiravir, Paxlovidallows the strings of viral RNA to be assembled correctly. It even allows those strings to be used to create viral proteins.
Paxlovid is designed with a SARS-CoV-2-specific protease in mind, so it works more specifically on this coronavirus than molnupiravir.
HOW EASY WILL THEY BE TO GET?
Unlike, Covid-19 vaccine or those treatments, not only did people have to make their way to clinics for their infusions, but hospitals and other facilities had to set up places where people could take their jab or dose. Still, the Covid pills come with a key challenge of their own. They are the most effective when given early in the infection, so people need to be able to get tested and get their prescription rapidly. So, any delay in getting diagnosed undercuts the power of these pills; even a day or two has real implications for a treatment meant to clear out an acute infection like Covid-19. Both Covid-9 vaccine and Covid-19 pills are not easy to get because of their limited stock and usage.
WILL IT AFFECT A PATIENT’S DNA?
This is really a question only for Merck’s molnupiravir, since it works by subtly corrupting parts into the coronavirus’s RNA sequence.
Once the virus has mutated too much, it can’t work so the is mission is accomplished. But there’s a theoretical chance that molnupiravir could also influence normal human DNA when it replicates, too. If mutations happen during that process, it could create serious trouble.
WHAT MIGHT THE NEW ANTIVIRALS MEAN FOR CANCER PATIENTS?
Because the new antiviral Pfizer is developing is a protease inhibitor, infectious disease specialists are familiar with how it works. So, these drugs have the potential to interfere with many therapies used to treat cancer.
These pills will be very helpful but they will not substitute for prevention or vaccination efforts because these are not medicines that are completely mild and harmless in terms of their drug interactions and toxicity.
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