- The South African Health Products Regulatory Authority recently approved a new COVID pill developed by pharmaceutical company Merck.
- Treating a person with Merck’s branded medication could cost up to R10 000 per person, making it an unaffordable option for most.
- Merck is letting other manufacturers make the drug at a lower cost — but private healthcare facilities won’t be able to buy it.
When COVID vaccines were being rolled out, Africa’s poor were left behind. So deals that will allow poorer countries to buy COVID medicines at an affordable price seem like a step in the right direction to make access more equitable. In theory.
At the end of last year, regulators in the United Kingdom and United States (US) approved two new COVID pills for emergency use. One was developed by Pfizer and the other by Merck (known as MSD, short for Merck Sharp & Dohme, outside of the US and Canada). These tablets lower someone’s chances of falling so sick with COVID that they need to be admitted to hospital or that they die from it.
On 17 February, the South African Health Products Regulatory Authority (Sahpra) approved MSD’s brand-name pill called Lagevrio for emergency use in South Africa. In Lagevrio, the active ingredient (the stuff that makes the medicine work) is called molnupiravir.
Will South Africa get it?
Simply because a treatment is approved for use by a country’s medicines regulator, doesn’t mean that the country’s health department has to buy it. Regulators merely assess whether medicines are safe and effective; they have no influence on whether a government decides to incorporate approved drugs in their treatment policies. For decisions on COVID treatments, South Africa’s health department has a group of experts, the National Essential Medicines List committee on COVID therapeutics (NEML), who advises them.
In the case of molnupiravir, the NEML has ruled against its use in the public sector — even if it’s produced as a cheaper generic drug.
In a press briefing last week, the committee’s Jeremy Nel explained that because molnupiravir is aimed at high-risk patients (people of 60 and older and those with comorbidities such as diabetes and heart disease) only, and has to be used within five days after someone had their first COVID symptoms, it’s not a practical choice for our public health sector.
The study participants on which molnupiravir’s efficicacy was tested, were also all unvaccinated, so the benefit of the drug will likely be lower for vaccinated people, Nel said, because COVID jabs already provide them with significant protection against falling seriously ill with the disease.
Sixty eight percent of people of 60 and older — research shows this is the group who are most likely to fall very sick with COVID — have had at least one COVID shot and about six out of ten have been fully vaccinated.
And, Nel says, because it can be difficult for people using the public health system to get tested — and receive their results — within five days after their first symptoms, this leaves a very small pool of people who will actually benefit from molnupiravir.
These things mean that if rolled out in the public sector, there’s a big chance that the drug will be given to people who won’t really benefit from it, Nel says. This will cost a huge amount of money without providing significant benefits, something a country with a limited health budget can’t afford.
What’s the deal?
Buying brand-name pills can be expensive, so opting for generic versions of a drug could be a solution for low-income countries.
A generic drug is one that works in the same way as the brand-name pill because it has the same active ingredient (molnupiravir in this case) but can be produced for less.
Cipla, a drug manufacturer that specialises in making generics, is already at work to produce a copy of MSD’s COVID pill. Because a generic medication has to be reviewed separately from the brand-name version, Cipla says they have also submitted an application to Sahpra and are waiting to hear whether it will be approved.
The Medicines Patent Pool is an organisation that helps make medications more affordable. It does this by working with pharmaceutical and generics manufacturers so the information around drugs is more accessible and in turn more pills can be made.
Granting someone a voluntary licence means the original patent holder allows other companies to also make their product, instead of retaining the exclusive right to production.
Because the licence is administered by the Medicines Patent Pool, approved generics manufacturers can obtain the rights through the pool rather than directly from the original developer.
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Going through the pool is beneficial to both the pharmaceutical developer and the manufacturing companies. That’s because it saves the developer from having to negotiate individual deals with each generics producer and it also helps make the agreements more transparent so everyone has the same conditions imposed on them. Ultimately, it also helps the consumer, because several suppliers will be putting a generic product into the market at the same time, which drives up competition and brings down the sale price.
The patent pool has, for instance, previously worked to make HIV treatments accessible by entering into agreements with patent holders for antiretroviral drugs.
MSD’s agreement with the patent pool allows a number of generics manufacturers to produce molnupiravir and distribute it to 105 low- and middle-income countries, which can go a long way towards preventing supply constraints in poorer countries.
But although South Africa has been included in the deal, our arrangement looks different from that of other countries because only the public sector will be allowed to access the generic pills.
The reason? South Africa as a country is too rich to be included in the agreement, yet our public healthcare sector is poor enough.
Leko Nkabinde, associate director of communications at MSD, explains that South Africa doesn’t fall into the bracket of low- and middle-income countries that MSD thinks won’t be able to afford buying the drug directly from them, based on data from the World Bank.
But, she says, because they recognise the high levels of inequality in the country and want to support fair, broad-based access, the country’s public sector was included.
Is MSD’s approach helpful?
Some say yes, some say no.
In an October statement, the World Health Organisation (WHO) and Unitaid described the agreement as “a positive step towards creating broader access to the treatment”.
Allowing generics manufacturers into the supply chain can also “shorten the time from approval of the medicine to its availability” in countries covered by the licence, the statement read.
But some advocacy groups say it’s not enough.
“Voluntary strategies, including voluntary licensing, allow [p]harma to retain control of the competition, markets and pricing while purporting to be a global good, [a] public health measure in the service of enhancing their image,” wrote the International Treatment Preparedness Coalition, a local group of treatment activists, in a November statement.
But even with its drawbacks, MSD’s approach is still further ahead than other pharmaceutical companies’ during the pandemic.
In addition to allowing generics manufacturers to make molnupiravir, MSD is also supporting production by sharing the recipe and expertise of how to combine everything together — something called technology transfer.
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In voluntary licence agreements that are negotiated privately with the original patent holder, the actual “know-how” of making the drug can be withheld. Vaccine manufacturers Pfizer and Moderna have, for example, continuously refused to share technical know-how with those attempting to recreate their mRNA jabs.
However, as the molnupiravir case has shown, the process is not foolproof. Several countries, mostly in South America, were left out of the deal completely and limitations were imposed on South Africa.
Gelise McCullough, head of communications at the Medicines Patent Pool says they tried “hard to negotiate the inclusion of [South Africa’s] private sector” in the deal, but “MSD wishes to keep the private sector in South Africa for themselves”.
A divided healthcare system
The Medicines Patent Pool licence agreement puts South Africa in an awkward position, as the private sector will have to negotiate their own deals with MSD to access the drug — likely at a higher cost.
While it’s unclear exactly how much it would cost for South Africa’s private sector to buy molnupiravir directly from MSD, it won’t be as cheap as the generics available to the public sector.
Another obstacle is that generics manufacturers would have to approach MSD for a separate deal that would allow them to produce the medication for the private healthcare facilities. But given that MSD already chose not to include the private sector in their licence agreement with the patent pool, it’s unlikely that they will be keen to strike a deal to cover these facilities later.
This previously happened with the HIV treatment dolutegrivir, for which the licence from pharmaceutical company ViiV specified access to only the public sector in certain countries. Delays in actually providing the drug in the public sector left people with limited options and some turned to the private sector, where they had to pay more to access a branded version of the medication.
The intention of MSD’s agreement with the patent pool is to cover the bulk of the population and those who likely cannot afford a more expensive version of the pill. But the logistical realities of public healthcare in South Africa, coupled with only a fairly small number of people set to get real benefit from the drug, dilutes the practical value of the agreement.
In the end it may mean that the medicine – whether the brand-name version or its generic counterpart – will be accessible only to people wealthy enough to afford a medical aid plan that provides it or to buy brand-name molnupiravir pills in cash. Medical schemes have not yet announced whether they would pay for the treatment and if so, which medical aid plans will make it available.
Mind the gap
Yet the reality isn’t so clear cut.
Because the quality of service is so much lower in the public than the private sector, people relying on public hospitals or clinics are unlikely to seek care quickly. It also means that people who should be relying on public healthcare sometimes turn to private facilities and pay out of pocket.
The exact number of people who fall into this overlap isn’t tracked very well in South Africa. But the best estimate comes from 2010 data, which shows that the proportion of people who rely only on public health services is likely closer to 63%. This leaves about a fifth of the population who would use a mix of both public and private facilities.
As a result, some people who economists assume should be relying on public hospitals and clinics based on their income may opt to use a private facility instead, where they’d have to foot the much higher bill for the medication themselves.
This group, who fall into the gap between the public and private sector, are at risk of missing out on access to molnupiravir, as they would unlikely be able to afford the branded pills prescribed at a private site. They would also miss out on the deal afforded to the public sector because they may not be diagnosed with COVID at state facilities.
Why make molnupiravir locally?
Cipla previously made an injectable drug called remdesivir at their Indian and South African plants. Even though the WHO advised against its use in 2020 because it wasn’t clear whether the drug had a meaningful effect on shortening COVID-related hospital stays, lowering the need for ventilation or improving patients’ outcomes, demand soared in the private sector.
Last year, when India experienced its deadly Delta wave, that country’s government banned exports of remdesivir, delaying supplies to the rest of the world. During this time, Cipla began doing tech transfer between its Indian and African factories, so that the continent would have capacity to make its own supplies if international movement of products became restricted.
The high demand for a COVID treatment during that time motivated the pharmaceutical company to enter the molnupiravir fray. Using their experience with remdesivir as a roadmap, the manufacturer set up to begin production of the pill.
The CEO of Cipla South Africa, Paul Miller, says that because this process of sharing knowledge and skills was already underway, both African facilities (one in South Africa and the other in Uganda) were able to begin producing molnupiravir by the end of 2021.
The medication can’t be sold in South Africa until it has been approved by Sahpra. But in the meantime, as an approved generics manufacturer, Cipla can begin preparing the pills.
Aspen, one of the largest pharmaceutical players on the continent, has, however, opted not to produce the antiviral in South Africa. The company is bottling Johnson & Johnson’s COVID jab at its Gqerberha plant.
“At this point Aspen has no plans to produce COVID antivirals in South Africa, but rather to source these under Aspen’s label from partners,” said Stavros Nicolaou, Aspen’s senior executive of strategic trade.
How a generic medication is made
Making a generic version of a medication involves several steps:
1. The first is making the active ingredient, in this case molnupiravir, which Cipla has done in South Africa (they got the know-how from their plant in India).
2. The manufacturer then has to ensure that what they’ve made is an exact copy of the original drug (molnupiravir) and that it will work in the same way. Generic manufacturers have to follow guidelines to show that their version of the medication is stable, so it won’t expire or change its structure in different climates.
3. The company then has to figure out the best way to encase the drug into a form that can be taken orally and check that, clinically, the pill behaves just like the original made by MSD.
In the case of molnupiravir, an additional step is added where the African-made products will be compared to the Indian-made capsules to see if they’re consistent.
4. All the data is then submitted to a country’s medicines regulator for approval. Regulators assess, amongst other things, if the generic pill matches its original counterpart.
This story looked at the details of the pharmaceutical company, Merck’s voluntary license agreement with the Medicines Patent Pool with regards to molnupiravir. It is the second story in a three-part series. Read part 1. Part 3 will explain why the South African health department has decided not to make use of the voluntary license agreement and will therefore not be procuring molnupiravir as a COVID treatment.‘
[28 February, 11:59: This story was amended to reflect the decision of South Africa’s National Essential Medicines List Committee to advise against the use of molnupiravir in the public sector.]