The looming COVID-19 treatment equity gap

It took less than two years for the most promising emerging oral treatment for COVID-19, Pfizer’s Paxlovid, to speed through development and to receive emergency use authorization from the U.S. Food and Drug Administration.

But a combination of production and regulatory hurdles means that it may be at least another year before a significant supply of Paxlovid or a generic equivalent is available in most low- and middle-income countries, according to research from the COVID Global Accountability Platform, or COVID GAP, led by Duke University.

At the same time, the 30 million courses of Paxlovid that Pfizer expected to be produced in the first half of 2022 have been purchased almost entirely by high-income countries, according to COVID GAP’s tallies.

That has raised alarm among academics and activists that the same inequities that appeared in the distribution of COVID-19 vaccines are being replicated when it comes to access to Paxlovid. They are pressing Pfizer and governments for a range of interventions, including making equitable shares of the current courses available to LMICs at not-for-profit pricing. They are also calling for steps such as accelerating licensing for generic manufacturers and sharing critical production knowledge with those producers that would speed up their ability to distribute the treatment.

“The nightmare that we’re sleepwalking into is upon us,” Rachel Cohen, the regional executive director of Drugs for Neglected Diseases initiative, said during a policy discussion on COVID-19 treatments organized by Public Citizen last week. “We have to do a huge number of things to widen the therapeutic window.”

Pfizer released results in December that confirmed Paxlovid reduced hospitalizations in high-risk COVID-19 patients by nearly 90%. With those outcomes, it leapfrogged molnupiravir, another antiviral manufactured by Merck, which has also been racing to the market but is less effective than Paxlovid — reducing hospitalizations by 30%.

Pfizer’s treatment was hailed as a “game changer” by U.S. President Joe Biden, but it has its limitations. Patients must start treatment within five days of symptoms appearing. That means not only is rapid testing infrastructure critical, but it must quickly connect patients who do test positive to the treatment — a linkage that is missing in many places in the global south.

The bigger limitation may be the lack of immediate availability of Paxlovid.

Pfizer is projected to produce 120 million courses before the end of 2022, though an estimated three-quarters are expected in the second half of the year. That would fall short of the 175 million courses COVID GAP projects will be needed this year if COVID-19 falls to endemic status — something WHO officials have repeatedly cautioned is not likely to happen anytime soon — and well below the 475 million courses that would be necessary if cases return to the rates before the omicron surge.

In November, Pfizer signed a voluntary license with the Medicines Patent Pool, or MPP, agreeing to share the patents and know-how that would allow for the production of generic versions of Paxlovid. The United Nations-backed MPP can then sublicense to manufacturers to supply 95 countries.

MPP is expected to announce the recipients of the sublicenses this month. That will signal the start of a process of development and testing of the generic formulations. In the current best-case scenario, COVID GAP predicts that the generic manufacturers could be prepared to file for World Health Organization prequalification by the second quarter of 2023. For many countries, prequalification is needed to jumpstart local regulatory approval processes.

This timeline hinges on Pfizer’s willingness to share significant knowledge with the generic manufacturers, including the active pharmaceutical ingredient, which is not a given.

There are other ways to accelerate the timeline: Donors could step in to help generic manufacturers increase their production capacity, as the Bill & Melinda Gates Foundation has done to speed the production of generic molnupiravir. Activists also called for WHO to accelerate a prequalification process they said can be bafflingly slow.

It “faces a backlog, lack of capacity, lack of funding,” said Sharonann Lynch, a senior scholar at Georgetown’s O’Neill Institute for National and Global Health Law. “There needs to be a rescue program for the WHO prequal program.”

Countries also need to begin preparing now to quickly take advantage of the treatments as they do become available. That means ramping up rapid testing, particularly self-testing, and linking it more directly to care. Experts are looking to leverage existing test-and-treat systems, such as those implemented by the President’s Malaria Initiative.

All of this — including the treatments, even at generic prices — will cost money.

Except “there is no money for this virtually anywhere in the system,” said Krishna Udayakumar, director of the Duke Global Health Innovation Center. “Unless somebody has money to buy product at whatever the price point is, they will not have availability.”

The lack of funds could scare away generic producers, worried they might invest in manufacturing a product that countries cannot afford to buy. Udayakumar called for high-income countries to enter into advance purchase agreements for the generics, which would incentivize potential manufacturers to actually commit to production. Regional bodies, such as the African Union, could also leverage pooled procurement mechanisms to guarantee demand.

Even if the MPP mechanism can be optimized, there is the risk that middle-income countries, including much of South America, will still be left out. They are not among the 95 countries granted access to Paxlovid under the MPP license and are unlikely to be able to compete with high-income countries to purchase the supplies Pfizer makes available.

Access advocates are calling on Pfizer to broaden availability by granting additional licenses and expanding the terms of the MPP agreement. Knowledge Ecology International is leading an effort in the Dominican Republic to encourage the government to approve an open compulsory license related to Paxlovid. If granted, it would allow for the introduction of generic versions of the treatment, even though Pfizer has applied for a domestic patent.

KEI’s Luis Gil Abinader said they would withdraw the compulsory license request if the Dominican Republic is added to the list of countries covered by the MPP license.

“That is our primary goal here, to expand the geographical scope of MPP license and expand generic distribution of generic Paxlovid,” he said during the policy discussion.

On a broader scale, activists are also continuing to pressure the World Trade Organization to approve a waiver of the Trade-Related Aspects of Intellectual Property Rights, or TRIPS, which would temporarily waive intellectual property protections of COVID-19 vaccines, treatments, and products.

While the timeline for availability of Paxlovid or an equivalent in LMICs is unresolved, generic production of molnupiravir is moving much faster, thanks in part to Merck’s decision to issue voluntary licenses for the treatment nearly a year ago. Some generic versions are already being reviewed for prequalification by WHO.

That could lead to a situation where molnupiravir is easily accessible in LMICs, while the more effective treatment, Paxlovid, remains largely restricted to high-income nations.

“Will countries and communities be satisfied with that?” Cohen asked. “Will the world accept a double standard?”