By guest contributors Rashi Jhunjhunwala, MD MA; Arturo Cervantes Trejo MD MPH DrPH; Pablo Tarcisio Uribe-Leitz MD MPH; John Lindsay-Poland, Keith Martin…
More than two years into a pandemic that has killed 15 million people, it seems we have learned nothing. When COVID-19 vaccines first became available over 18 months ago, global manufacturing capacity was limited. Public sector investment flowed into vaccine development and capacity expansion, but scale-up was constrained by the failure to share technology with emerging initiatives in low- and middle-income countries. Instruments such as COVAX were established to distribute the scarce supply of vaccines more equitably, but floundered in large part because high-income countries undercut the solidarity mechanism with bilateral supply deals.
Over a year later, efficacious COVID-19 antivirals have emerged, and there is again a gap between need and supply. But this time the situation is less inevitable and more absurd: high-income countries have again reserved nearly all early supplies, but the scarcity is largely artificial. Generic copies are far easier and faster to produce than vaccines, but are constrained by intellectual property. The crisis in antiviral supply is now an economic choice, not an unavoidable material reality.
COVID-19 antiviral landscape
Two oral antivirals have emerged to treat COVID-19. Molnupiravir received emergency use authorization from the FDA and a conditional recommendation by WHO. Ritonavir-boosted nirmatrelvir (Paxlovid), whose clinical trials so far have shown significantly greater efficacy in unvaccinated high-risk populations, is the first antiviral to receive a “strong recommendation” from WHO. The first wave of therapeutics – casirivimab/imdevimab and tocilizumab – were dominated by intravenously administered monoclonal antibodies, which were both complex and costly to manufacture as well as resource-intensive to administer. In contrast, newer oral antivirals such as molnupiravir and nirmatrelavir-ritonavir are relatively simple and cheap to manufacture, and can be dispensed at a pharmacy or primary care center. This has raised hopes for a global test and treat strategy: with wide availability of testing and antivirals, in addition to vaccination, many lives could be saved.
A reality check on access
If you are reading a certain genre of self-congratulatory news articles – or if you are a glass-half-full kind of person – access to antivirals has been an unprecedented success. Merck and Pfizer, the proprietors of molnupiravir and nirmatrelvir/ritonavir respectively, licensed their antiviral drug patents to the Medicines Patent Pool (MPP). The MPP has in turn signed agreements with generic companies to supply 95 (for nirmatrelvir/ritonavir) and 105 (for molnupiravir) low- and middle-income countries (Figure). Pfizer has also publicized their recent agreement with UNICEF to supply up to 4 million treatment courses of nirmatrelvir/ritonavir to 95 low- and middle-income countries. The agreement stirred controversy: UNICEF reportedly abandoned joint negotiations alongside other agencies to instead broker a non-transparent, bilateral deal with Pfizer, keeping the procurement price under wraps.
In reality, Pfizer’s entire production capacity has already been committed to a handful of rich countries, representing about 14% of global population. The other 86% of the world will have to wait until the end of the year, if not 2023, to be able to purchase from Pfizer.[i] As with vaccines, there has been no independent oversight or transparency on manufacturing capacity. In Pfizer’s contract with the US government (obtained only through a freedom of information request), production timelines are described as “aspirational in nature”, with no real consequences should Pfizer fail to deliver the promised volumes on time.
The UNICEF agreement provides a trickle of alternative supply, but the math does not add up: the United States has one treatment course for every 16 people, while UNICEF is somehow supposed to allocate one per 1,600 people.[ii] The generic supply facilitated through the MPP is good news for countries included in the licensing agreement, but globally, there is no real plan for the 2.5 billion people in countries that have not secured scarce supply and are also excluded from MPP licences: generic manufacture would risk lawsuits for patent infringement, and Pfizer has run out of manufacturing capacity.[iii] In effect, for these 124 countries, there is no nirmatrelvir/ritonavir available for purchase at any price.
The Dominican Republic, Chile, Peru, and Colombia are pursuing the only other pathway to accessing antivirals: compulsory licensing. Compulsory licensing, protected under international law, allows governments to import or manufacture generic medicines without the permission of the patent holder, effectively circumventing the patent, where a government cannot secure affordable access through negotiations with the patent holder. The justification for using this mechanism for nirmatrelvir/ritonavir is obvious: the global pandemic has killed 15 million people, with further millions of cases expected this winter, and without generic access, there is no supply available in these countries, at any price. This is a tried and tested legal pathway, used by at least 40 countries for HIV, cancer, and other medicines since the 1990s.
Pfizer has responded aggressively to what should have been a straightforward case in the Dominican Republic, arguing that its Paxlovid patent is “akin to a human right and, as a result, any limitation to that right – such as a compulsory license – would violate Dominican law”. The bitter irony to this argument is that Pfizer has resisted calls for both its vaccine and antiviral to be made available to the world on human rights grounds. No one is asking Pfizer to treat the world as a charitable endeavor (although with record revenues of $100 billion this year, they certainly could afford to). Instead, Pfizer is simply being asked to allow countries to import or manufacture the nirmatrelvir/ritonavir that Pfizer is unable to supply themselves.
If this is corporate social responsibility, the current terms of engagement by Pfizer make clear to which parts of society Pfizer feels responsible: the shareholders. Away from public promises of equitable access, Pfizer says the quiet part out loud in filings to the United States Securities and Exchange Commission outlining potential risks to revenue, which include “legal or regulatory action by various stakeholders or governments that could potentially result in us…agreeing not to enforce or being restricted from enforcing intellectual property related to our products, including … our oral COVID-19 treatment.”
How can we explain Pfizer’s hardline approach, when it is already making unprecedented profits and has sold out of nirmatrelvir/ritonavir? First, Pfizer likely expects lower prices anywhere in the world will eventually cut into its margins in the most profitable markets. Pfizer’s largest customer, the US government, has a “Most Favored Nation” pricing clause in its nirmatrelvir/ritonavir contract, meaning if Canada, France, Germany, Italy, Japan, Switzerland, or the United Kingdom negotiates lower prices, Pfizer is contractually obligated to match this price in the United States. It is only a matter of time before political pressure in one of these countries leads them to narrow the gap between global generic prices ($25/course) and Pfizer’s current prices ($530/course). Second, middle-income markets, now evidently not a priority for Pfizer, may in the future become important should new, more effective antivirals emerge and tank demand for Pfizer’s antiviral in high-income countries. Again locked out of both early supply and generic licensing deals, middle-income countries might consider purchasing the next-best product. Such medicine markets – tiered by both price and efficacy according to wealth – are not uncommon for diseases like diabetes and cancer.
There is another explanation for what at first appears to be an unnecessarily cruel and senseless business decision to block middle-income countries from purchasing nirmatrelvir/ritonavir elsewhere, when Pfizer itself has no supply to sell. In the current paradigm of medicine pricing, pharmaceutical corporations will sometimes offer voluntary access initiatives to the poorest countries, as long as these initiatives remain totally under their control, and as long as they pose no danger whatsoever to future blockbusters.To cede ground on compulsory licensing would be to concede that countries have a legitimate right to use all available legal avenues to protect the health of their people: a slippery slope towards affordable access to medicines.
A way forward
We have been here before. Throughout the pandemic, there have been calls for global leaders to not ignore the lessons of HIV/AIDS – governments should act swiftly, guided by the human right to health as paramount. Given the weight of the facts in the nirmatrelvir/ritonavir compulsory licensing cases in Central and South America, it is likely at least some will succeed. How many other countries will risk the ire of pharmaceutical multinationals in order to secure access to these important new COVID-19 treatments remains to be seen.
A more transformational, long-term solution would require governments to find a way to safeguard access to treatments of pressing global importance in the future. Many of the same countries that led the way to ensure that the Doha Declaration was more than a piece of paper— that countries would actually be able to use TRIPS flexibilities in practice to address the AIDS crisis in the early 2000s – now lead in trying to pass the “TRIPS waiver”, which would suspend intellectual property rights on COVID-19 related products. The waiver has been stuck in the debating stage at the World Trade Organization since October 2020. Current drafts have watered down the proposal to cover only vaccines, and only for a limited time.
Some have said that it is easier to imagine the end of the world than the end of capitalism. Perhaps similarly, it is easier to imagine the next pandemic facing these same problems again, than it is to imagine substantive changes in the IP and R&D systems that underlie the problems. That’s not to say there aren’t green shoots of alternative systems— no longer just ideas, initiatives like the COVID moonshot and WHO mRNA vaccine technology transfer hub are building new models of R&D and technology transfer, centering equity and access from the ground up. Access to COVID-19 medicines has seen some, limited victories: the MPP licensing agreement is far better than nothing and will save lives. But for transformative change, we’ll have to wait for next time.
[i] Author’s own calculation. Population data from the United Nations Population Division. 86% includes all countries that have not purchased from Pfizer, and does not consider within-country access barriers.
[ii] Author’s own calculation. Population data from the United Nations Population Division. 1/1600 calculated assuming 4 million doses available for all low- and- middle income countries. Only 95 countries are eligible to purchase the UNICEF supply, but as this list has not been made public, all low and middle income countries are assumed here.
[iii] Author’s own calculation. Population data from the United Nations Population Division. 2.5 billion calculated as population within countries that have 1) not purchased Paxlovid and 2) are not included in the MPP license.
About the author:
Melissa Barber is a doctoral candidate in Population Health Sciences in the Department of Global Health and Population at Harvard University. Her research interests include health economics, pharmaceutical policy, intellectual property, and the political economy of the biomedical innovation system and its impacts on health. She has worked on access to medicines issues for the World Health Organization, Médecins Sans Frontières Access Campaign, the Global Fund to Fight AIDS, Tuberculosis and Malaria, the World Bank, the Clinton Health Access Initiative, and the Addressing the Challenge and Constraints of Insulin Sources and Supply (ACCISS) study. She can be found on Twitter at @mellabarb