Why Paxlovid is still not available in many LMICs

When Albert Bourla, CEO at Pfizer, tested positive for COVID-19 in mid-August, he announced on Twitter that he was feeling well, thanks to four doses of his company’s vaccine and access to Paxlovid, Pfizer’s COVID-19 antiviral drug.

Not everyone, however, has received boosters, and many in low- and middle-income countries still don’t have access to Paxlovid or even know about it.

According to a recent report that looked at access to COVID-19 tools in 14 countries and territories, several health workers from Nigeria, Madagascar, and Haiti have never heard of novel antivirals for COVID-19 including Paxlovid. In countries, such as Peru and Jamaica, Paxlovid has not yet been approved for use. In the few countries where it’s been made available, such as Somalia, supplies were significantly limited.

“[W]e have requested 3000 plus courses, but we got only 300 courses,” said Dr. Mamunur Rahman Malik, WHO representative for Somalia.

“So, in a country with a population of fifteen million people, I don’t think it is enough in terms of managing the critical care for COVID-19 patients,” he was quoted as saying in the report.

Some experts point to pricing as a barrier — although it’s unclear how much a course of treatment really costs. Ali Mokdad, professor of global health at the Institute for Health Metrics and Evaluation, said only high-income countries, and the rich in several countries, are able to access the drug at the moment.

“I'm from Lebanon. I know in Lebanon, some rich people have been able to secure it, but they pay a lot for it. They have somebody in the U.S. or somebody in Europe in the U.K., or in France and they send the money and they're willing to buy it and there'll be a prescription and it will be bought for them and shipped to Lebanon the next day. That's not true for the majority. The 99% of people in Lebanon, they can’t afford [it],” he said.

While the drug has been in use in several countries such as the United States, where it’s been given emergency use authorization since December 2021, it’s still out of reach for many populations.

“We are at a point right now that we have a medical drug that will save lives, but it is out of the hands or the reach of many people on this planet,” Mokdad added.

And this could get worse if policies change and governments allow for an increase in medication for antivirals. Amid reports of COVID-19 rebound, the U.S. Food and Drug Administration has asked Pfizer to test for the effects of an additional course of Paxlovid among people who again experience COVID-19 symptoms after taking the drug. U.S. President Joe Biden and his wife, Jill, were among those who experienced this recurrence.

While this is not the policy right now, Mokdad says if it happens in the U.S., “then automatically, the supplies [will be] cut in half for the rest of the world.”

‘Protracted’ negotiations

Paxlovid is one of the two oral COVID-19 antivirals that have received emergency use authorization from regulatory agencies such as the U.S. FDA. It is recommended to be taken by patients who test positive for COVID-19 who are experiencing mild to moderate symptoms and are at risk of developing severe disease and hospitalization. In April, the World Health Organization recommended the drug, describing it as the “best therapeutic choice for high-risk patients to date.”

But even then, WHO had expressed concerns regarding low- and middle-income countries’ access to the drug. The health agency doesn't yet have a clear picture of the availability of the medicine and which countries may be involved in purchasing it. A licensing agreement allowing generic production of the drug is also limited. None of the selected companies are based in Africa, and the generic versions can only be made available in 95 countries, effectively leaving out several middle-income countries. The generic versions may also only be available by the end of 2022 or early 2023.

Several months on from WHO’s recommendation, many countries don’t have access to the therapeutic, and it’s unclear what happened to deals made in previous months by international aid agencies. UNICEF signed a supply agreement with Pfizer in March for the procurement of up to 4 million courses of Paxlovid. Devex reached out to the agency, as well as Pfizer, but has yet to receive a response as of this writing.

Unitaid, co-lead of the therapeutics pillar of the Access to COVID-19 Tools Accelerator, or ACT-A, told Devex in an email that agencies that are part of ACT-A are working to facilitate access to Paxlovid as they await the availability of generic alternatives. However, negotiations with Pfizer are taking time.

Access to Paxlovid would be useful for countries as they await generic versions of the drug. But a number of factors are prolonging negotiations with Pfizer, thus delaying the drug’s introduction in countries.

“High prices, lack of price transparency and differentiated pricing approaches hamper access in low- and middle-income countries (LMICs). This situation is further complicated by regulatory and compliance challenges, as well as competing health priorities in these countries,” wrote Carmen Perez Casas, strategy senior manager at Unitaid. But the progress in the production of more affordable generics offers alternatives to countries, she added.

“The first generic nirmatrelvir/ritonavir from an Indian-based manufacturer is now under assessment by the WHO Prequalification Programme,” she said. Several Indian manufacturers were chosen to produce generic versions of Pfizer’s drug, as part of sublicensing agreements with the Medicines Patent Pool announced in May.

While there are challenges in the introduction of Paxlovid, Casas said ACT-A partners have started deliveries of molnupiravir — the other oral COVID-19 antiviral by Merck, Ridgeback Biotherapeutics, and Emory University — and that “generic supplies are expected to follow shortly.”

A source privy to discussions at ACT-A who requested anonymity as they are not authorized to speak on the matter said that a recent report from the ACT-A Facilitation Council joint working group on diagnostics and therapeutics highlighted how the ongoing negotiations with Pfizer on Paxlovid are delaying access to the drug. The report also recommended multilateral development banks conduct feasibility assessments on the creation of regional manufacturing hubs for therapeutics, and that future medical countermeasure platforms should look at the role of price transparency in accessing therapeutics, said the source.

Next week, however, a consortium involving multiple organizations, including Pfizer and donors, such as the Open Society Foundations and the Conrad N. Hilton Foundation, is expected to announce how they will be supporting governments to introduce and scale-up access to oral COVID-19 antivirals in high-risk populations in 10 low- and middle-income countries. The countries include Ghana, Kenya, Laos, Malawi, Nigeria, Rwanda, South Africa, Uganda, Zambia, and Zimbabwe.

The cost of lack of access

Last week, WHO said that the world has reached another tragic milestone: 1 million people have died from COVID-19 this year.

“We cannot say we are learning to live with COVID-19 when 1 million people have died with COVID-19 this year alone, when we are two-and-a-half years into the pandemic and have all the tools necessary to prevent these deaths,” WHO Director-General Tedros Adhanom Ghebreyesus said in a news briefing.

According to the latest modeling by IHME, scaling up antiviral access could save the lives of over 9,000 people globally by Nov. 1.

The number is small given the current limited availability of antivirals. But if access to antivirals remain the same by November, the opposite could happen: more lives lost and more pressure on hospitals that would have to cater to severe COVID-19 cases on top of other patient needs.

“Paxlovid and others have been around for a while right now, and already in 2022 we have 1 million deaths from COVID-19. A lot of these mortalities could have been prevented,” Mokdad said.