covid pills
GENERIC COVID PILLS? Five (5) Indian pharmaceutical firms are set to produce generic versions in India, which could significantly help boost supplies for less-developed countries. Image Credit: Gulf News

Highlights

  • Three new COVID-specific anti-viral pills are in advanced clinical trials.
  • If one — or all three — would be approved, the breakthrough could drastically change the course of the pandemic, say experts.
  • The frontrunner, Merck’s molnupiravir, already has a pre-approval price of $705 per course following US government pre-orders.
  • Two others — one each developed by Pfizer and Roche/Atea — are in final clinical trials, too.
  • The actual price is unclear, but is expected to drop significantly with generics.
  • More data readouts from trials expected by November.

The good news: People newly-infected with COVID-19 might soon have access to what essentially is a pill for SARS-CoV-2.

COVID pills are all the rage right now, as several oral antiviral medications specifically developed against SARS-CoV-2 are about to hit the finish line. Three are in advanced stages of clinical trials, phases II/III, of which Merck’s molnupiravir is the front-runner.

The good news: People newly-infected with COVID-19 might soon have access to what essentially is a pill for SARS-CoV-2. Trials are promising. If, or when, approved, they could further boost the world’s fight against the pandemic, which has so far left 5 million dead.

Merck has announced molnupiravir cuts the risk of hospitalisation and death from the virus by 50%, based on the initial data read-out.

Here's the lowdown on the COVID pills:

What are the three COVID pills on trial’ where the molnupiravir stand?

The three candidate antivirals dashing towards the finish line are: molnupiravir, ritonavir, and AT-527.

They’re all oral medications. Among the three, the Merck-developed molnuvirapir is leading the pack, with initial data analysis of a trial involving 1,850 participants showing it cuts hospitalisations and deaths by half.

Based on their trial data, all three are expected to complete clinical trials by November.

Covid pills
Image Credit: Gulf News / Jay Hilotin

What are the end points of the COVID pill trials?

Molnupiravir:

The study aims to evaluate the safety, tolerability and efficacy of molnupiravir (MK-4482) compared to placebo. The primary hypothesis is that molnupiravir is superior to placebo as assessed by the percentage of participants who are hospitalized and/or die through Day 29

50% EFFECTIVE: No patients given molnupiravir died during trial
Merck announced that 7.3% of patients who received molnupiravir (28/385) were hospitalised through Day 29 of the study.

On the other hand, 14.1% of patients given placebo (53/377) were either hospitalised or died as a result of COVID-19 through Day 29. That’s a 50% efficacy, based on the initial data analysis.

Additionally, no patients that were given molnupiravir died, whereas eight of those given the placebo did. Merck said it was already already seeking emergency-use authorisation in the US.

Ritonavir:

The study seeks to determine whether PF-07321332/ritonavir is safe and effective for the treatment of adults who are ill with COVID-19 and do not need to be in the hospital, but are at an increased risk of developing severe illness. Study visits will be conducted at a participant's home or another non-clinic location if available. The total study duration is up to 24 weeks.

AT-527:

This study evaluates the efficacy, safety, antiviral activity, and pharmacokinetics of study drug RO7496998 (AT-527) compared to placebo in non-hospitalised adult and adolescent participants with mild to moderate coronavirus disease 2019 (COVID-19) in the outpatient setting.

What are the advantages of having COVID-19 pills?

The pills pose a number of important advantages.

First:

In the early stages of the infection, the pill can be already taken at home (if available). So people who are newly-infected with the virus could use it outside of hospitals. This could greatly help avoid healthcare facilities from being overwhelmed.

Second:

They’re specific to the COVID virus. Until now, hospitals have been using a repurposed drug remdesivir — developed to treat Ebola — to curb the damage done by a COVID infection, but its effectiveness is limited. On the other hand, monoclonal antibodies also can attack the virus in early infection, but they're in short supply, not easy to administer and quite pricey. They have to be given either intravenously, which makes administration even more expensive, with locations designated for treatment.

Third:

Ease of logistics and administration. The new pills, if proven safe and effective, could be the equivalent of antibiotics pills or a flu tablet that could keep people out of the hospital, curb complications, say experts.

So is it a 'game-changer'? Will vaccines become unnecessary if, and when the COVID pills are rollout?

If regulators deem the trial data to be acceptable based on their proof of work in reducing COVID hospitalisations and deaths, the new generation of oral medications could be a game changer. The anti-viral pill could offer an easy-to-swallow early-intervention tool against COVID, preventing the bulk of cases from progressing further.

That would significantly alter the fight against coronavirus. Meanwhile, approved COVID vaccines are already proven safe and effective and had been rolled out in the hundreds of millions across the world, but there's not enough of it for the entire planet.

As the global death toll climbed past 5 million, Dr Anthony S. Fauci, adviser on the pandemic to US President Joe Biden, warned that people in his country should not wait to be jabbed just because they believe they can take the pill. While the new medicine may decrease a person’s risk, Fauci said the best way to be protected is by avoiding infection, though inoculation.

Who are the drugs makers behind them?

Merck, known as MSD outside the United States and Canada, is the developer of molnupiravir. Pfizer, for its part started the early-stage clinical trial for ritonavir drug. Roche collaborated with Atea Pharmaceuticals to develop AT-527 as an oral treatment for COVID-19 patients.

Why does it take time for antiviral drugs to develop?

One reason it takes time for antiviral drugs to be developed is because they're so specific to the viruses causing disease. Merck conducted the molnupiravir clinical trials jointly with Ridgeback Biotherapeutics (a biotech company based in Miami Florida). It has also conducted trials with Indian pharmaceutical companies.

However, work on the broad-spectrum antiviral started more than 10 years ago. Any drug development effort is a time and money-intensive endeavour. Merck, for example, also tried to develop COVID vaccine, which the company abandoned in January after it failed to generate desired immune responses. Merck decided to focus on the pills instead.

$705

price per course of monlupinavir, based on an the $1.2 billion advanced orders of the US government for 1.7 million courses

How much is the cost of each molnupiravir course?

About $705 per, based on an the $1.2 billion orders placed by the US government for 1.7 million courses of the pill from Merck. The orders were “advanced” as the clinical trials had not been completed yet, and is contingent on approval by drug regulators. US health authorities plan to give the pills for free.

How many pills will be prescribed for each course?

Merck said patients will take four capsules twice a day for five days — 40 pills over the course of the treatment. The regimen is familiar to anyone who has taken an antibiotic.

What about side effects?

Merck did not report any serious side effects among volunteers in its clinical trial. Any side effects, which typically involve mild complaints like headaches, can be hard to distinguish from feeling ill from COVID, researchers said.

Will patients get it without a prescription?

No. In the US, people will need to get a prescription, which they'll fill at a pharmacy.

Isn't the $705 price tag per course too high?

Whether that will be the actual cost, remains unclear at this point. Merck (known as MSD outside the US and Canada) have committed to “plans to implement a tiered pricing approach based on World Bank country income criteria to reflect countries’ relative ability to finance their health response to the pandemic,” said Prof Stephen Evans, Professor of Pharmacoepidemiology, London School of Hygiene & Tropical Medicine.

“Many anti-viral drugs of this type are very expensive and for those unable to be vaccinated but who get COVID-19 disease, having an alternative is good news.”

What’s the price of the generics version of the pill?

Nothing has been announced yet. On June 29, 2021, Reuters reported that five Indian generic drugmakers — including Cipla, Dr Reddy's Laboratories, Sun Pharmaceutical Industries, Torrent Pharmaceuticals and Emcure Pharmaceuticals — have partnered with Merck to expand production of molnupiravir.

These are "non-exclusive voluntary licensing agreements”, aimed to speed up and expand access to molnupiravir. This could boost the drug’s availability in the subcontinent.

Will the COVID pills be available in other countries?

The deal with Indian drugmakers gave them license to make and supply molnupiravir to India and more than 100 low- and middle-income countries following approvals or emergency authorisation by local regulatory agencies, Merck said in late April.