COVID-19 pills are coming. Urgent action is needed to ensure equitable global access.

For much of the COVID-19 pandemic, vaccines have been the primary focus to slow the spread of the virus. However, amid rising infection rates and low global vaccination coverage, effective therapeutics that can prevent severe disease could be a game changer. But only if we learn from the inequitable vaccine rollout and ensure global access from the beginning.

Several treatments have been approved but are primarily used in high-income countries. Monoclonal antibody (mAb) therapy has proven effective at preventing high-risk patients with mild-to-moderate disease from developing severe disease and being hospitalized. But mAb therapy is expensive, and is administered via infusion or injection which requires medical infrastructure, trained staff, equipment (that can add further costs), and refrigerated transport and storage. All of these factors make mAb therapy challenging to use in low- and middle-income countries (LMICs). And we cannot be sure they will be effective against new variants.

Oral therapeutics hold significant advantages in terms of ease of administration, storage and transport requirements, manufacturing complexity, and cost. Pfizer’s Paxlovid (PF-07321332; ritonavir) looks especially promising – the latest data show an 89% reduction in hospitalization or death among high-risk adults with COVID-19. Paxlovid has not yet received regulatory approval anywhere but is under review by the U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA). (Merck’s molnupiravir has received authorization in the UK is also under review by the FDA and EMA. However, lower efficacy (30%) compared to Paxlovid (89%) and concerns about its use in pregnant women are likely to mean lower demand for this option.)  

Given the high protection provided by Paxlovid, it is imperative that we make this drug available worldwide, particularly in countries with low vaccination rates. Pfizer has already taken steps to facilitate access by making agreements with the Medicines Patent Pool (MPP) to license their molecules to manufacturers in 95 LMICs, and committing to tiered pricing based on income category, including not-for-profit pricing in low-income countries. (Merck has also made an agreement with the MPP as well as separate licensing deals with generic manufacturers in India. But, as noted above, for LMICs with limited resources to investment in therapeutics, Paxlovid likely represents better value.)

These are important, positive steps from Pfizer, but more actions are needed from global leaders to ensure timely, equitable access to the new oral therapies. Just as we saw with COVID-19 vaccines over the past year, high income countries are still likely to receive supply before LMICs as a result of advanced purchase agreements. A handful of high-income countries have already made deals for supply of Pfizer’s pill including the US which has purchased 10 million courses to be delivered by end of 2022. In fact, Pfizer has already shipped its antiviral for distribution across Europe and the US for immediate use upon authorization, which may come within the next week. Other countries will not have that same advantage.

These drugs have the potential to be gamechangers for the treatment of COVID-19, when given early in illness and particularly in high-risk patients. They are also likely to be effective against all the known Covid-19 variants. But while early steps have been made to address the challenges of patents and price, there are other critical hurdles that must be addressed to make antivirals available and avoid the inequitable distribution we saw with COVID-19 vaccines.

1.      Regulatory Authorization: The imminent regulatory authorizations in the U.S. and Europe does not translate to approvals in other countries. The drugs in principle must also receive local regulatory authorization or approval before being used. Sublicensees through the MPP also may need their product to receive regulatory approval separately from Pfizer or Merck’s product. In many LMICs, regulatory authorities are understaffed or under-resourced, and approval processes can be lengthy, delaying access to new drugs. Programs such as PEPFAR and the Global Fund to Fight AIDS, Tuberculosis and Malaria have played a pivotal role in helping countries gain quicker access to new products for these diseases. Drugs obtained using funds from these programs can receive approval by a Stringent Drug Regulatory Authority (SRA) – such as the FDA – or WHO prequalification rather than local regulatory approval. A similar model can be used to help LMICs gain faster access to COVID-19 antivirals.

2.      Manufacturing Scale-Up: Pfizer is investing up to $1 billion to support manufacturing and distribution of Paxlovid and has reported that it expects to produce 180,000 courses (number of doses needed to treat one patient) of Paxlovid by the end of 2021, and 80 million by the end of 2022. Merck plans to produce 10 million courses of molnupiravir by yearend, with plans to ramp up to 20 million in 2022. While clear estimates of need are still lacking, there is no doubt that demand will quickly outstrip supply. Licensing deals with generic manufacturers and the MPP will help bring on added manufacturing support – and lower prices – but this will not happen immediately. Sublicensees through MPP have not yet been revealed for either Paxlovid or molnupiravir, and once they have been obtained it will take time to get production online and, in some cases, for technology transfers to take place. Further, Pfizer and Merck’s licensing deals notably leave out several upper-middle income countries, particularly in Latin America, some of which have ample manufacturing capacity and high disease burden. While the companies have made commitments to tiered pricing for middle-income countries, this exclusion will likely limit access in these countries and is a missed opportunity to scale up local manufacturing.

3.      Testing Capacity: Treatment with these new antivirals requires a positive COVID-19 test and must be started within the first 3-5 days of symptom onset. Without easily accessible high-quality tests with fast results, these drugs cannot be effectively deployed on a large scale. This is a concern even in countries such as the U.S. which is already conducting 3.4 tests per 1,000 people per day. Testing data in many LMICs is not available, and those that are reporting have much lower rates (less than 1 test per 1,000 people per day). LMICs need urgent support to ramp up their testing capacity. Many countries, particularly in sub-Saharan Africa, have strong experience with test-and-treat models for HIV/AIDS programs. It should be possible to use a similar model for COVID-19, with the right support and investments.

Most experts now believe that COVID-19 will not be eradicated and will become endemic. Even with effective vaccines, to move from crisis-mode to long-term containment, our goal must be to make COVID-19 a more treatable, less deadly disease. That will require effective oral therapeutics available everywhere. The life-saving potential of these medicines can only be realized if people in need have access to them.

More attention must be paid NOW to oral therapeutics and the great task ahead of scaling up access. The companies know from their experience with HIV/AIDS what steps are needed. Global leaders also need to apply the lessons from the past with swift, coordinated actions to address these other access hurdles. A strategy is urgently needed to support generic production, procurement, distribution, and use of these new oral therapeutics.

COVID GAP will be taking a deeper dive into the topic of access to oral therapeutics, looking more closely at manufacturing capacity, supply, and price as well as commitments and targets to improve equitable access to treatments. In addition to our analysis, we will provide data-driven insights and actionable recommendations for stakeholders (planned publication in January 2022).

 

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