The U.K. was the first country to approve a COVID-19 vaccine; it has now become the first to approve an at-home treatment for COVID. On Thursday, the medicines regulator, MHRA, green-lit the antiviral drug molnupiravir, produced by Ridgeback Biotherapeutics and Merck & Co. and shown in trials to halve the risk of hospitalization or death in those with mild to moderate disease.
Health Secretary Sajid Javid called it a “historic day for our country.” For once that might not be an overstatement. Beyond Britain, the new drug should be a reminder of the importance of antivirals in the fight against this and future pandemics. Friday’s announcement by Pfizer Inc. of even better results for its home remedy — an 89% reduction of hospitalizations and deaths in late-stage trials — suggest it won’t be far behind. Pfizer, whose shares jumped on the news, is seeking emergency use authorization in the U.S.
The molnupiravir approval and Pfizer development couldn’t be timelier for the U.K.. Britain has had a stubbornly high COVID-19 infection rate. Although the most recent wave has not led to a marked increase in deaths from the virus, hospitals face a gargantuan backlog of delayed procedures, COVID-19 wards are fuller than is comfortable and there are worries that a bad flu season could tip an overstretched health service into deeper crisis.
Even though we have vaccines and better in-hospital treatments such as dexamethasone, a safe way to treat COVID-19 at home has been seen as key to living with the virus. As immunity from vaccines wane, more people who are fully vaccinated are contracting COVID-19, increasing the risks of transmission as well as post-viral illnesses and Long COVID.
Molnupiravir will be prescribed only for those with at least one risk factor for developing serious disease, such as obesity, diabetes or advanced age (over 60s). It comes in pill form, which makes it easy to administer at home and unlike Gilead Science’s remdesivir, the other approved treatment, which is administered intravenously in hospitals for more serious cases.
Rolling out a therapeutic has been a U.K. government priority in part because of the pressures on the National Health Service. Back in May, Prime Minister Boris Johnson promised that Britain would soon find a weapon to “stop COVID in its tracks.” A new task force, modeled after the highly successful Vaccines Taskforce, was set up to identify therapeutics to be used once people were infected.
Last month, the Antivirals Taskforce announced deals for two new treatments. One for 480,000 courses of molnupiravir; the other for 250,000 courses of the Pfizer treatment that includes ritonavir (a medication used to treat HIV infections) along with PF-07321332 (which is designed to block the work of a key enzyme that the virus needs to multiply).
These drugs will also be a boon for their makers. Merck, which plans to make 20 million courses in 2022 on top of 10 million this year, has said it expects molnupiravir to generate as much as $7 billion in global revenue by the end of next year (compared to $14 billion in sales last year of its blockbuster cancer drug Keytruda and $5 billion for its diabetes drug Januvia) — a boon to a company whose marquee products have been affected by the pandemic slump in medical screening and care. Pfizer is a little further behind, expecting to make 180,000 packs of its treatment by the end of this year but ramping up to 50 million by the end of 2022. Shares in the company jumped 11% in early trading Friday morning.
If these developments provide a fillip to the therapeutics industry generally, that would be a good thing. Viruses are hard to drug since they are constantly changing; of the 220 viruses known to infect humans, there are only 10 or so effective antivirals. Drug discovery for infectious diseases has generally not been a big priority among pharmaceutical companies — unsurprising since development costs (easily over $1 billion) and the time it takes to bring a new drug to market (easily a decade) make them high-risk and potentially low-financial-reward projects.
Antiviral testing also requires very high levels of biosafety in facilities, which are expensive to build and entail significant training. Only a small percentage of drugs that make it to clinical trials recover their initial capital investment. Work often gets under way for a virus that fades before medical progress is made, and so the project gets shelved. This happened during the 2003 SARS outbreak.
Given the cost and time it takes to develop new antivirals, it’s no surprise that our best hope for treating COVID-19 comes from drugs that have been dusted off and are now being repurposed. Molnupiravir wasn’t conceived as a treatment for COVID-19; it was developed at Emory University’s nonprofit company Drug Innovation Ventures at Emory (DRIVE) to treat a Venezuelan equine encephalitis virus. The new Pfizer treatment has been repurposed from one developed during the SARS crisis.
A number of antiviral candidates are now being developed. The pandemic has highlighted the importance of a strategy to support broad-spectrum antivirals as opposed to drugs that seek to counter just one virus.
The treatment could be a huge help in the fight against severe disease from COVID-19 in developing countries too. Last week, Merck announced it had signed licensing agreements for broad access to the drug in 105 low— and middle-income countries once regulatory approval is received. This allows generic versions of the drug to be manufactured, though much depends on testing regimes in these countries and distribution channels as the drug needs to be taken within days of infection.
As with any drug, there are also risks. While Merck has said it’s comfortable that the drug will be safe if used as intended, some researchers say more safety data is needed. The concern is that the compound’s “mutagenic” properties (the drug works by forcing the virus to mutate against itself) could cause damage to the host or accelerate the virus’s own ability to develop resistance. Pregnant women were excluded from trials, and both men and women had to abstain from sex or use contraceptives. It will be interesting to see whether the FDA agrees with the MHRA; the U.S. has already purchased 1.7 million courses for $1.2 billion, which breaks down to about $700 for a five-day course. The Pfizer drug, a so-called protease inhibitor that prevents the virus from replicating, may be an easier decision.
For Britain and anywhere else that licenses these new treatments, the delicate balance will be in ensuring that this new line of defense doesn’t dampen uptake of booster shots. These are far more effective since they prevent people getting ill in most cases.
While there is lots to celebrate about new treatments and vaccines, a virus that is still claiming a sizable share of health care resources and personal cost among those infected demands continued vigilance.