Two new oral treatments for COVID may prevent deaths and severe cases of COVID, but South Africa’s medicines regulator has yet to receive registration application from the respective manufacturers, Pfizer and MSD.
GroundUp writes that a new generation of antiviral pills shows promising results in preventing severe COVID disease. These are called Paxlovid, developed by Pfizer, and molnupiravir (Lagevrio), developed by MSD (Merck, Sharp and Dohme, known as Merck in the US).
Pfizer claims Paxlovid reduces the risk of hospitalisation by nearly 90%, while MSD claims molnupiravir reduces the risk by about 50%.
Yuven Gounden, public relations manager of the SA Health Products Regulatory Authority (SAHPRA) said that SAHPRA has not received any applications for the registration of these products, and neither manufacturer has signalled that it will be applying. “SAHPRA can only take steps once an application has been submitted.”
Foster Mohale, director of Media Relations for the national Health Department, said that the department doesn’t comment on medical products not approved for use in the country by the independent regulatory body.
“There is no plan to procure or secure something which is not approved for use, and even if approved, it doesn’t automatically translate into a need to procure,” he said. Mohale referred questions about interactions between manufacturers and the South African government to SAHPRA.
But other health officials confirmed that there had, in fact, been engagement between the original manufacturers — and prospective generic manufacturers — and the South African government. The claims made by both manufacturers are tantalising, but neither trial result has been peer-reviewed yet and no data has yet been made available to South Africa’s health authorities, let alone the public. As such, the claims of success are being treated with caution.
What do we know about these medicines?
According to Pfizer’s 5 November announcement, patients treated on a course of Paxlovid saw an “89% reduction in risk of COVID-19-related hospitalisation or death from any cause, compared with placebo in patients treated within three days of symptom onset”. No deaths were recorded in the treatment group, and similar results were seen with those who received the treatment within five days of symptom onset.
On 16 November Pfizer announced that it would be seeking emergency use authorisation from the US medicines regulator, the Food and Drug Administration (FDA). MSD submitted its emergency use authorisation to the FDA on 11 October.
MSD’s results for molnupiravir are also eye-catching. According to an announcement on 1 October, “Molnupiravir reduced the risk of hospitalisation or death by approximately 50%” compared with patients who received a placebo.
Like Paxlovid, “No deaths were reported in patients who received molnupiravir, as compared to eight deaths in patients who received placebo”.
On the strength of these results, molnupiravir has been authorised for use by the United Kingdom’s medicines regulator. According to a 10 November article in Nature, the world’s leading science journal, “Several generic-medicines companies have already started to manufacture the drug”.
But for the rest of us who have no access to the data, extreme caution is needed. Scientific medicine cannot be practised by press release.
How they work
Both treatments are antiviral courses, taken as pills, over five days. Treatment should begin during the first few days of a symptomatic infection.
Paxlovid is a protease inhibitor that prevents the SARS-CoV-2 virus from creating successful copies of itself. Paxlovid is taken with an existing drug, ritonavir. Ritonavir is an HIV drug — it boosts the amount of protease inhibitor absorbed by the body. Without ritonavir, the liver will identify the protease inhibitor and remove it from the body.
Molnupiravir also works by attacking the virus at the point of its reproduction. However, the idea behind molnupiravir is that it introduces itself into the virus, and creates mutations. These mutations are more easily dealt with by the patient’s immune system, leading to a successful recovery.
A leading infectious diseases expert told GroundUp that there are advantages to MSD’s drug — there is a lower likelihood that molnupiravir will react with a patient’s chronic medication, and it does not require any amplification with a drug like ritonavir.
Do we need to buy them?
It is not clear what the pandemic still holds in store for us. These antiviral treatments are not supposed to be the main defence against severe COVID. Vaccines are. But by 14 November, only a third of South Africa’s adult population — 13.4m adults — was fully vaccinated against COVID. This is nowhere near the Department of Health’s goal of vaccinating 67% of our total population — about 40m people — by the end of 2021.
The share of people over 60 who are vaccinated is higher, at 56%, and this will help reduce future hospitalisations.
On 17 November, the South African COVID-19 Modelling Consortium (SACMC) released a report looking at the prospects of a fourth wave in South Africa. In the absence of a new variant, SACMC projects the size of the fourth wave (measured in hospital admissions) to be smaller than the third wave.
But, if a variant does emerge (as has been the case with previous waves), the hospitalisations are expected to reach capacity again.
We will not be able to get access to these treatments by the end of the year, but even faced with smaller waves to come, keeping deaths and hospitalisations down should be a priority.
How much do they cost?
No prices for either treatment are openly available, but we can extrapolate at least one price point from the pre-orders made by the US government. America has now bought a total of 3.1m courses of molnupiravir for $2.2bn. This amounts to about $710 per course of treatment, or about R11,000.
On 16 November, Bloomberg reported that the US had agreed to purchase 10m courses of Paxlovid treatment. According to Reuters, Pfizer is looking to sell its course of Paxlovid for about $700, or about R10,900.
These are expensive treatments, and demand will be high relative to supply. In the same Reuters article, Pfizer said that it was looking to produce at least 21m courses of treatment by mid-2022.
But hospital resources are scarce too. The national health department has just had its budget reduced by nearly 5% in real terms, over the medium term. This might lead health officials to be cautious about unplanned expenditures on new treatments — but it also might want to consider keeping people out of very costly hospital care.
In May 2020, Medscheme, a major South African medical scheme, announced that the cost per patient hospitalised with COVID was R150,000. Discovery reported that its average cost (also in May 2020) was R87,000, with the treatment of patients on ventilators costing on average R340,000. According to a study published in BMC Health Services Research, the cost per admission for severe and critical COVID patients in general wards was more than R75,000 and for those subsequently admitted to Intensive Care Units (ICUs), the cost per admission was more than R100,000.
Many people with COVID infections require hospitalisation. On 3 August, in the middle of the third wave, there were 15,788 people admitted to hospitals at that stage, according to the National Institute for Communicable Diseases (NICD).
According to the most recent NICD report from 16 November, there were 3,599 COVID patients in hospitals.
The flies in the ointment
These treatments work, or are claimed to work, because they prevent the uninhibited replication of the virus in a person’s body. This means that they must be administered in the early stages of a person’s COVID infection. The announced results focused on treatment starting within the first three days of symptoms appearing.
This is a problem for South Africa. If one were to wait for confirmation of COVID infection by PCR tests, which have a turnaround for results of two days, it might be too late. Added impracticalities are the high costs of these tests and the relative inaccessibility of testing sites, which discourage people from seeking confirmation of a suspected infection.
The most obvious solution is to reverse the ban on home testing using low-cost antigen tests. These tests are very good at identifying if someone has a COVID infection once symptoms emerge.
Alternatively, public health officials might decide to forego testing altogether, and instead rely on a checklist of symptoms. If someone exhibits symptoms that seem likely to be COVID, they would then be placed on a course of treatment.
Either/or?
While Paxlovid’s results are, on the face of it, superior to molnupiravir, its reliance on ritonavir might make it a less favoured option. According to a local expert, ritonavir would cause problems for drugs that metabolise in the liver. These include some medications for diabetes and pain relief.
Meanwhile, molnupiravir is a novel treatment. This means that its manufacture may be more difficult to achieve for generics firms. Further, the manner in which it works — creating mutations in the RNA of the virus — has some researchers worried about possible side effects. Others have discounted the risk for harm to patients, as the duration of treatment is short.
What about us?
Willis Angira, Pfizer’s External Communications Manager for East and Southern Africa, said that they could not share any specifics on negotiations between Pfizer and the South African government.
Vuyo Mjekula, MSD’s director of Policy, Communications & Public Health for South Africa and sub-Saharan Africa said: “MSD has included South Africa in its agreement with the voluntary licensing partners, specifically to service the South African public sector. MSD has also initiated discussions with the national Department of Health, a number of private sector partners and other key stakeholders to discuss early access opportunities for South Africa.
“In addition to this, we have entered into an agreement with the Medicines Patent Pool (MPP),” said Mjekula. Pfizer has also entered into an agreement with the MPP for Paxlovid.
The MPP is a UN-backed forum that negotiates access to patented medicines, for the benefit of people living in lower-income countries. It was created in 2010, largely as a response to the HIV epidemic, but has expanded its mandate to include hepatitis C, tuberculosis, and essential medicines for other diseases.
MSD has agreed that generics manufacturers in countries covered by the MPP licence, which includes South Africa, can produce molnupiravir for use in those countries without paying royalties, assuming the treatment is approved for use. Pfizer has likewise agreed to a similar deal with the MPP.
We asked local generic giant Aspen Pharmacare if they have an interest in the production of these treatments, if they have the immediate capacity to produce either treatment, or, as we have been led to understand, if they are in negotiations to produce either Paxlovid or molnupiravir under these licences,
We were told: “Aspen is not able to provide any comment in this regard.”
What this means is that while the South African public sector could get access to these treatments at a reduced cost from generics firms, the private sector would need to procure these medications for the original license holders directly.
GroundUp article – New Covid treatments might be slow to arrive in SA (Creative Commons Licence)
See more from MedicalBrief archives:
MSD to seek SAHPRA approval for its promising COVID-19 pill
Pfizer to deliver generic version of its COVID pill to 95 countries
Merck’s COVID antiviral pill may halve the risk of hospitalisation and death