Merck’s Molnupiravir – Overcoming impending barriers to affordable global access

Now that there are press reports on the efficacy of Merck’s molnupiravir as an outpatient antiviral therapy for newly diagnosed cases of COVID-19 where the patient has at least one underlying risk factor and treatment can start within 5 days of first symptoms, it is important to assess potential barriers affecting affordable global access to molnupiravir.  We have every reason to believe that there will be shortages of supply, needlessly high prices, and inadequate, overly restrictive voluntary licenses that will exclude countless people in urgent need around the world, including fully 50% of people living in low-income and middle-income countries (L/MICs) alone.  This will lead to avoidable disease progression, more long-covid, and increased deaths.

Governments must not be allowed to repeat the odious mistakes made in placating profiteering by vaccine manufacturers, treating them with kid gloves while they prioritized defending their monopoly rights despite any and all human cost. Emory, the original developer of molnupiravir, benefitted from financial support from the National Institute of Allergy and Infectious Diseases of other public funders, meaning that once again taxpayers will pay twice over for fruits of scientific advancement. The U.S. government also holds rights related to patents related to molnupiravir, giving it additional leverage. Merck’s proposed voluntary licenses are woefully inadequate and will not bring about the global access to molnupiravir needed–Merck’s intellectual property must take a back seat to rapidly expanding truly global access to cheap generic versions of this treatment. 

Supply shortages anticipated, and rich countries are likely to procure all initial doses

Merck has previously predicted that it can make enough pills for 10 million courses of treatment by the end of 2021.  The U.S. government had already conditionally procured 1.7 million courses of treatment for $1.2 billion even before clinical trial readouts and has options for millions more according to Dr. Fauci.  This echoes the U.S. notorious hoarding of remdesivir, monoclonal antibodies, and vaccines starting in the first half of 2020.  Although molnupiravir is reported to be only 50% effective in reducing hospitalizations and death, and thus less effective than infusion-based monoclonal antibody treatments being manufactured by Regeneron and Eli Lilly, molnupiravir, once it receives emergency use authorization, will be much easier to administer as an oral pill and three times cheaper even at the profiteering price Merck has set.  In addition to selling preferentially to the U.S., Merck has also indicated that it is in negotiations with other buyers. If past is prelude to the future, high-income countries will be among those first buyers and very little stock, if any, will be left for L/MICs.

Merck says it has been scaling up production at least since June of 2021.  Although Merck has not definitively announced its future production capacity, it appears that it will be limited in terms of meeting potential demand.  Although it is hard to predict how many annual infections there will be in 2022, test-confirmed infections in the first half of 2021 totaled 37 million in high-income countries and 61 million in L/MICs, a half year total of 98 million infections.  Assuming that 80% of all infections will produce even mild and moderate disease, on an annual basis there could be 156 million people potentially eligible for treatment with molnupiravir (and/or other proven antivirals) in 2022.  Even if Merck were to double its production capacity in 2022 (it has no stated plans to do so), it is clear that it can meet only a fraction of demand.

Merck might argue that global targets should be reduced because it only tested molnupiravir in patients with at least one risk factor, a decision that may initially constrain molnupiravir’s authorized uses and treatment guidelines.  Even so, such patients are thought to comprise at least 25% of the population (38 million according to confirmed figures), a total Merck alone clearly cannot supply.  

Of course, we know that the number of COVID-19 infections globally is much greater than those revealed by confirmed PCR tests.  According to some researchers, “Severe under-ascertainment of COVID-19 cases was found to be universal across U.S. states and countries worldwide. In 25 out of the 50 countries, actual cumulative cases were estimated to be 5–20 times greater than the confirmed cases.” Some of these cases are certain to involve asymptomatic patients, but others involve cases where people were not tested because of test shortages or because people never made it to health services.  These undercounted populations contributed to the estimate that the total of actual COVID-19 deaths globally is at least 2 times higher than the number reported.  

Moreover, there is no compelling reason to think that clinicians should not treat all people who have confirmed infections.  Firstly, identifying “people most at risk” is underinclusive as many people without underlying conditions have suffered COVID-19 morbidity and mortality.  Second, there is every reason to think that reducing viral loads with early antiviral treatment and isolated homecare will reduce onward disease transmission.  Finally, there is biologic plausibility to the idea that effective antiviral therapy could decrease the incidence and severity of long-covid.

Merck’s voluntary licenses to generic suppliers will be insufficient to fill the treatment gap

Merck will likely point to its existing voluntary licensing with eight Indian generic companies as evidence that it is already providing for additional production capacity. However, Merck has only licensed 104 countries as detailed in the map below (shared by that ACT-Accelerator).  Middle-income countries excluded from the license had 30 million infections in the first half of 2021, 50% of all infections in L/MICs.  Even if the eight Indian generics make it to market and can satisfy this demand in licensed territories, Merck will be unable to meet the remaining 70% of global need.  There is little doubt that Merck will serve U.S. and other high-income country demand first and foremost, and that middle-income demand cannot and will not be met. Although Merck has confirmed that it is in negotiations with the Medicines Patent Pool for a revised license for molnupiravir, there is no indication to date that it intends to expand the license’s territorial coverage.  Letting Merck unilaterally carve up the world into commercially profitable zones and generic-access zones is completely unacceptable.  

Merck’s prices are exorbitant, far in excess of projected costs of production 

Merck’s contract price to the U.S. was $700 per course of treatment.  Although this might seem to be a discount compared with Regeneron’s $2200 price, that is the wrong comparator. $700 per course is far in excess of anticipated costs of production, projected to start at $17.74 per course of treatment based on the current cost of the active pharmaceutical product and falling to $3.86-$8.64 per course of treatment with optimized production methods.  In other words, Merck is charging the U.S. more than 35 times a sustainable generic price (cost plus 10%).  Although Merck has promised to use discount pricing in its sales to L/MICs according to World Bank income-group categories, there is no precedent that it would charge as little as the best generic price.  One of the reasons Merck restricted its licensed territories is that it intends to profit from its prices in excluded countries, particularly Upper-Middle Income Countries (UMICs) that have suffered huge numbers of preventable deaths and where company-by-company, product-by-product negotiations with vaccine manufacturers have revealed the tremendous asymmetry in power that must not be replicated with molnupiravir. Merck has retained market hegemony in a form where it categorically cannot meet all demand and yet it will continue to profiteer off of the sales it can make. 

One additional reason to focus on price is that it will be highly desirable to ultimately use two or more antivirals to treat mild and moderate COVID-19 so as to reduce the risk of disease resistance.  Molnupiravir needs to be widely available because the cost of combination therapies will unavoidably be somewhat higher.

The solution to these barriers is to override Merck’s intellectual property monopolies and expanding generic supply and competition

Merck is playing with people’s lives while endangering global recovery from the COVID-19 pandemic. The Biden Administration and other high-income country governments might believe that not treating people abroad will not affect populations at home, but obviously, this is delusional – as it has been with vaccines. Global access to antiviral treatment is a moral imperative. Quality, timely treatment access will also reduce the likelihood of development of additional mutations and reduce onward transmission.  Treating people abroad will conserve scarce medical resources, reduce burdens of long-covid, and reduce economic disruptions that occur when people cannot work because of worsening disease.  Although vaccines, in the long run, will hopefully continue to reduce the number of people needing treatment, treatment will still be needed for those who are unvaccinated or who experience breakthrough infections.  

Merck’s intellectual property monopolies should not be permitted to obstruct global treatment access.  Merck should be forced to allow generic competition.  The U.S. government should challenge Merck to license molnupiravir more broadly, including by expanding the scope of coverage of any voluntary license with the Medicine Patent Pool to include all LICs and MICs.  Alternatively, countries facing shortages and high prices should issue compulsory licenses, and to do so on a coordinated basis if at all possible.  There is a vast array of companies in LICs and MICs that can produce small-molecule medicines of assured quality once patent barriers are removed.  And they will be able to do so even more affordably once optimized production methods are better known.  However, the problem with compulsory licenses is that they must be issued country-by-country.  Thus, an even better solution would involve the long-delayed adoption of the temporary waiver of intellectual property right obligation at the World Trade Organization, which would allow countries to export and import generic molnupiravir without fear of state-to-state dispute settlement or infringement claims.

Greater molnupiravir access must be matched with a test-and-treat strategy

Molnupiravir treatment must be initiated within 5 days of symptom onset.  Thus, it will be essential that access to antigen rapid diagnostic tests (Ag RDTs) also be expanded greatly in LMICs.  Ag RDTs should be widely available first at the community level and shortly thereafter at home so that infection can be detected as soon as possible.  Equally important, access to treatment must begin immediately when antivirals will be most effective at reducing viral load, preventing disease progression, and preventing onward infection.  Much expanded access to Ag RDTs, beyond the tens of millions to the billions, and access to antivirals for 100-plus million patients not 10 million will have to be matched with community and patient health literacy, health provider training, and logistics support. Only then will the promise of out-patient antiviral treatment have the desired impact—saving the lives of half the people infected, from the ravages of this deadly pandemic.