Antiviral COVID-19 pills developed by U.S. firms promise to be a pandemic game-changer. But even as some countries begin to roll out the highly anticipated drugs, others have raised concerns that shortages and manufacturing chaos could hamper global supply.
“We heard there is not enough supply to ensure the world access to these medicines,” Colombian Health Minister Fernando Ruiz said. He added that he had “so many worries” that global access to the pills would end up mirroring the vaccine shortages.
Ruiz has reasons to fear. Wealthier countries have already advance purchased much of the supply of treatments expected to be available in the first half of 2022. Effective use of the pills — which include Pfizer’s Paxlovid and Merck’s molnupiravir, codeveloped with Ridgeback Biotherapeutics and Emory University — also requires access to coronavirus tests, which remain scarce in many places.
However, some signs indicate that the distribution of the drugs, which were shown in studies to be effective in lowering the risk of hospitalization and death, could shake out quite differently from how vaccines have. Generic versions are already hitting the shelves in India and Bangladesh, and both Pfizer and Merck have reached deals to share the license for the drugs.
“It seems more like the Wild West than vaccines did,” said Andrea Taylor, who works with a team at Duke University tracking early orders for the pills.
In the early stages at least, inequity is likely to persist. A World Health Organization report produced this month warns of a “high risk of shortages” of Paxlovid for low- and lower-middle-income countries until generic versions are more widely available, which it said was likely to be the second half of 2022.
If there are shortages, it would “mirror what we’ve all just been through on vaccines,” said Peter Maybarduk of the advocacy group Public Citizen. “That’s a travesty.”
While coronavirus vaccines work to build immunity before infection, antiviral treatments such as Paxlovid and molnupiravir are prescribed for use soon after symptoms appear.
Both have approval from the U.S. Food and Drug Administration but data released in November showed that molnupiravir was less effective than initial clinical trials predicted, reducing the risk of hospitalization and death by only 30% when given within five days of the onset of symptoms. Pfizer’s antiviral drug was found to reduce hospitalizations and death by 88% in that same time frame.
Unlike other COVID treatments that have to be administered intravenously, Paxlovid and molnupiravir are pills. For Paxlovid, a single treatment course includes 30 pills, while molnupiravir requires 40. The treatments use small molecule technology, far easier to replicate than the technology needed for vaccines.
“Any decent manufacturer of medicines can make it,” Pfizer CEO Albert Bourla said of Paxlovid at a health care conference this week.
Pfizer and Merck both agreed last year to share the licenses for their drugs with the United Nations-backed Medicine Patent Pool, or MPP, a nonprofit that aims to improve access to medicines, as well as with specific producers — which has not been done for any coronavirus vaccine.
Under the agreement, each company would allow generic versions of the drugs to cover more than half of the world’s population, with Pfizer and Merck retaining the market control for high-income and upper-middle income countries.
The generic versions of the drug would not only aid manufacturing, but they would probably be cheaper. In early deals made with the United States, Merck sold molnupiravir for $712 a treatment course, and Pfizer sold Paxlovid for $530. Brook Baker, a professor of law at Northeastern University who tracks pharmaceutical deals, estimates generics of molnupiravir could be sold for as little as $10 per treatment.
While the MPP deals are ambitious, this won’t immediately lead to a production boom. Drugmakers will need time to draw up manufacturing plans, and the treatments will still be subject to regulatory approval.
Wealthy nations are buying up the first batches of pills from Pfizer and Merck. So far, a dozen countries have made deals to purchase Paxlovid, according to Duke’s research. The agreements include sales of more than 26 million courses of treatment, including 20 million courses earmarked for the United States, which paid over $10 billion for the drugs.
Pfizer expects to produce just 30 million courses in total by the second quarter of 2022 and 120 million by the end of the year, according to media relations manager Kit Longley. The United States will receive 10 million course treatments by June and another 10 million by September, Longley said.
Merck has seen a smaller number of orders — about 8.6 million courses from 15 countries — including 12 high-income and three middle-income nations. The company aims to produce just 30 million courses by the end of the year.
Both Pfizer and Merck are in talks with larger buyers such as the European Union, with more orders expected to come in.
Generic versions of both drugs are already available in South Asia, where some manufacturers have worked outside of the MPP process. At least 13 drug companies in India have been approved to produce their own version of molnupiravir, with several already on the market, while two Bangladeshi firms so far are producing their own version of Paxlovid.
Both countries have well-established pharmaceutical sectors that often produce generic drugs. For now, prices may be prohibitive: A course of a generic version of molnupiravir in India can cost less than $30, but the two available Paxlovid generics in Bangladesh are considerably more expensive, nearing $200.
Cost is not the only issue. India‘s drugs controller general said that there were “major safety concerns” around molnupiravir, including potential pregnancy and lactation complications.
“It’s not just about high income versus middle income versus low income,” said Leena Menghaney, the regional head of Doctors Without Borders in South Asia. “It’s about rich people against poor people.”
Multiple groups have stepped in to try to ensure that low-income countries get doses of the antivirals. The Gates Foundation announced last year that it had committed up to $120 million to make molnupiravir available in lower-income countries.
The African Union said this week that it is in talks with Pfizer for access to Paxlovid. There are also legal cases in Chile from pharmacist groups and a nonprofit to compel the government to issue a compulsory license for the Pfizer drug.
John McGrath, head of external manufacturing and supply at Merck, said that the company has aimed to make sure that the drug is rolled out across the board.
“When we set up initially, we were looking at vaccine nationalism on the go,” McGrath said. “We were trying to avoid that and really look at how we can get the global supply of this product as quickly as possible.”
Still, the drug companies will maintain control over supply to upper- and upper-middle-income countries not covered by the MPP license, including many in Latin America.
Experts also warn that a lack of testing in some countries could have a major impact on the rollout of the drugs. Modeling by the World Health Organization has estimated that 6 out of 7 COVID-19 cases in Africa go undetected, in large part because of a lack of both supply and demand for tests.
Both Pfizer and Merck are now testing whether the treatments could be taken preventively after potential exposure to the virus. If so, the pills could play a significant role in stopping symptomatic disease.
That would reduce the need for testing, experts say. It would also increase demand for the treatments.