- South Africa’s medicines regulator has approved the COVID treatment molnupiravir. But that doesn’t mean the country’s public sector will use the drug.
- The decision to buy a medication for national roll-out is handled by the national health department and an expert committee has advised them that molnupiravir isn’t the right choice for South Africa.
- Private hospitals and clinics are still able to make their own decision about whether they want to buy the pills.
It’s not because molnupiravir isn’t a good drug — in fact, the World Health Organisation backs it, (albeit with some conditions). But it’s not the right drug for South Africa’s public health sector. This means the government will likely not be rolling it out at state clinics.
In South Africa, there are two bodies that have a say about whether a COVID treatment could be available in the country.
The first is the South African Health Products Regulatory Authority (Sahpra), which looks at whether a medication is safe and effective. For the public sector, there is another group: the National Essential Medicines List Committee on COVID-19 Therapeutics (COVID-19 NEMLC), whose role is to say whether a COVID drug would be a good option for South Africa.
But even if both Saphra and this advisory committee back a medicine, it’s then still up to the national or provincial health departments to choose whether to actually buy it or not.
Understanding the system
Sahpra makes sure that every type of health product in South Africa – things like medicines, vaccines, supplements, diagnostic tests or medical devices – is safe, works the way the manufacturer says it does and is of good quality. Without Saphra approval, a health product cannot be sold legally in the country.
For the review process, a manufacturer has to provide a stack of paperwork that includes the raw data for all the clinical and quality tests done up to that point.
Properly assessing a product “means looking at absolutely everything”, Marc Blockman, a professor of clinical pharmacology at the University of Cape Town, previously told Bhekisisa.
That means every piece of information available is given to the regulator to look through, from cell and animal studies to that of the human trials and quality control tests. Providing raw data also means that reviewers are able to assess much more than what would be published in a scientific journal.
But going through everything in that level of detail can take some time, which is why some reviews may take longer than others.
“You can’t sacrifice safety for speed,” explains Blockman.
Sahpra can use something called a reliance mechanism, which allows them to look at the analysis by another trustworthy regulatory body, such as the US Food and Drug Administration or the European Medicines Agency, to help them make their decision faster.
If a product is considered safe and effective and meets Saphra’s requirements, it gets approved for use in the country.
Finding the right fit
Getting Sahpra approval is the first test any medicine has to pass to get rolled out in the country. But when it comes to COVID treatments (which excludes vaccines), the expert committee set up specifically during the pandemic, looks at whether it will be practical for a specific drug to be used in South Africa.
They ultimately consider whether the potential benefit from the drug would be worth the money and effort needed to dispense it at clinics or public hospitals. Although the final say about buying a drug lies with the health department, the committee’s input helps the government to decide whether or not it will be money well spent.
Since April 2020, the committee has looked at 26 possible COVID treatment options and submitted their recommendations to the department.
They keep their eye on a “watchlist” of possible drugs, says committee chair Andy Parrish. If new data is published, in the form of a scientific paper or a regulatory review, a treatment can move up the evaluation list if the evidence about its safety and how well it works (efficacy) is sound.
And that’s exactly what happened at the end of last year, when the results of a clinical trial of molnupiravir, which involved close to 1 500 participants, were published in the New England Journal of Medicine. The study found that the drug would benefit three people for every 100 who received it.
But even though the results showed that the drug is safe and effective, and Sahpra has since approved the brand-name version of the pill, called Lagevrio, the advisory committee did not recommend it for use in South Africa.
Why molnupiravir isn’t right for us
To approve a drug, Sahpra only needs to confirm that it’s safe and works as the manufacturer claims it does.
Molnupiravir ticks both these boxes.
The pill is meant to lower the chance of someone who is unvaccinated and has a high risk of getting very sick from COVID ending up in hospital or dying. And in that group of people it works.
However, when the COVID-19 NEMLC looks at the efficacy of a drug, they consider how many people will benefit from it within a South African environment.
And, for a pill that could only help three people for every 100 treated, molnupiravir came with a few too many conditions.
1. The available data only applies to unvaccinated people
Molnupiravir was tested only in unvaccinated people who had a high risk of getting very ill because they were elderly or had another health condition like diabetes.
Although the clinical results showed that the drug can protect people in this group against serious illness, it’s unclear how much it would benefit people who already have some immunity from being vaccinated.
“There just isn’t data on the population that we’re interested in at the moment,” explains Parrish. This includes people who have either been vaccinated or have developed natural immunity, through exposure to the virus, which is estimated to be at least 60% of South Africans.
Just over two-thirds of people older than 60 have already been vaccinated in South Africa, and can also get booster shots. This means that the pool of people the drug would help the most (because age is the strongest indicator of how sick someone will get with COVID) is already quite small.
But vaccinated people can still get infected with the COVID virus (these are called breakthrough infections) as we saw during South Africa’s Omicron wave. That means we would need more information around how well molnupiravir works in those who are already immunised.
Things might change, though. As the drug is rolled out in other countries, new data could be published on how well the pill works in vaccinated people. If that happens, the committee will re-assess whether they should change their recommendation.
2. It’s not clear if the drug will be safe for pregnant women
Clinical trials generally don’t include pregnant women because of unknown effects on a developing foetus. So there isn’t any information yet about how the medication affects this group.
But animal studies have thrown up a red flag. Merck, the original developer of the medication, reported that studies in rats and rabbits found that the drug could lead to developmental problems with the foetus, such as bones or some organs not growing correctly and in some cases death.
Because of these safety concerns, Sahpra (along with other regulatory bodies) approved molnupiravir on the condition that it should not be given to pregnant women. Another rule is that women who could get pregnant should be on contraception while taking these COVID pills and for another four days after finishing the treatment.
This is a responsible condition for a regulator to put in place, but it makes implementation impractical.
Every woman who’d need the treatment would either have to be screened to make sure she’s not pregnant or be sure to use some form of contraception, which could add additional pressure on the public health system (for example by having to prescribe birth control or doing extra tests).
Parrish explains that the advisory committee had to consider the practical implications of rolling out the treatment.
“So that’s where things become very problematic,” he says.
3. The window from testing to treatment is very small
For molnupiravir to lower your chances of falling very ill from COVID, you have to start taking the pills within five days of showing symptoms. This means you have to get tested and get a confirmed result within that period.
In general, it takes around one day to get a COVID test result in South Africa. But Parrish says based on their experience, the wait can likely be longer in the public sector. The longer it takes to know if you have COVID, the less time there is to start taking the tablets.
In addition, the drug can only be used in people who have mild to moderate symptoms. So if you’re in hospital already, it’s too late for the pills to work.
This introduces a potential problem, as it’s uncertain whether people with few symptoms will get tested soon enough or whether they’d even want to take the medication given that they are not yet seriously ill.
An ongoing analysis that monitors infection levels in South Africa shows that only around 10% of actual COVID cases in the country are reported. That’s because many people have no or only mild symptoms, and so don’t bother to get tested.
4. It comes with an unknown price tag
Buying the brand-name pills (which is the version currently approved by Sahpra) will likely be pricey.
Based on how much the United States spent on the medicine — it could cost up to R10 000 to treat one person with molnupuravir — the South African health department is unlikely to be able to afford it.
Although cost is not the most important factor when it comes to the advisory committee’s recommendation, it can play a big role in whether the health department decides to buy the drug.
For example, last year the committee recommended a medication called baracitinib as a suitable COVID treatment option.
But despite strong evidence backing its use, including support from the World Health Organisation and a positive recommendation from the COVID-19 NEMLC, it never actually made it to public hospitals and clinics.
That’s because even with the go-ahead from the national health department, it was up to each province to decide if their budget would allow for the extra expense, says Parrish.
Could South Africa still buy it?
Although a cheaper, generic version of the brand-name molnupiravir pill could become available, the government can’t even consider buying it until it too gets Sahpra’s stamp of approval.
And even then, the health department’s communications director, Foster Mohale, says: “There is no immediate decision and plan to procure the treatment because the evaluation showed that it is not significantly better than how we treat COVID-19 at the moment.”
But this constraint does not apply to the private sector, because they’re not bound by the advisory committee’s recommendations.
Says Parrish: “The bottom line is that the private sector has no obligation whatsoever to even read, let alone follow, a recommendation in the public sector.”