Gilead Sciences, which makes the six-monthly anti-HIV injection, has approached the SA Health Products Regulatory Authority (SAHPRA) to discuss how to get the shot registered locally as fast as possible.
Cheaper, generic versions of the jab, which contains the antiretroviral drug lenacapavir, will be sold to 120 countries with high HIV rates, with South Africa being among them, while generic shots are likely to become available in 2027, said Mitchell Warren, executive director of the New York-based advocacy organisation Avac.
In the meantime, Gilead has committed to selling its branded injection to 18 countries, of which South Africa is also one, at a no-profit price, Bhekisisa reports.
Trial results published in July showed that lenacapavir, injected under the skin, provided 100% protection to HIV-negative women aged 16 to 25.
Earlier this month, at the 5th HIV Research for Prevention Conference in Peru, researchers announced that another study showed that lenacapavir also dramatically reduced the chances of HIV infection for other groups of people – gay men, trans and non-binary people aged 16 and older, who have sex with partners classified as male at birth, by 96%.
Although South Africa’s new HIV infections have decreased considerably since 2010, the country has fallen behind in reaching a UN target to reduce new infections by 90% by 2030 (compared with 2010).
In 2010, South Africa had about 350 000 new infections, but in 2023, there were 150 000 new cases – almost five times more than planned.
Long-acting jabs like lenacapavir could potentially help to reduce these statistics significantly.
Delays from SAHPRA in reviewing
On 2 October, Gilead said it would start a series of global regulatory filings by the end of 2024, but didn’t specify with which countries it would start. Although lenacapavir is registered as treatment for HIV-infected people who have become resistant to other ARVs in the US, Canada and some European countries, no country has yet approved the drug as a medicine to prevent HIV-negative people from contracting the virus.
But while SAHPRA has the technical know-how to evaluate data for new medicines, and the WHO considers it a stable and well-functioning regulator – one of Africa’s top six – it is severely understaffed and unable to review new medicines as fast as it would like to, resulting in delays for both new and generic medicines to go to market, CEO Boitumelo Semete-Makokotlela said recently.
She told Bhekisisa: “That is why our conversations with Gilead focused on how SAPHRA can get help to expedite the review process for lenacapavir by using mechanisms like EU Medicines for All (EU-M4all).”
How EU-M4All works
EU-M4all runs parallel to the European Medicine Agency’s (EMA) approval process, helping countries outside the EU to accelerate their own checks because they can rely on already-scrutinised data.
So far, EU-M4All has been used to speed up the review process for 15 medicines, such as vaccines for malaria and dengue fever.
Semete-Makokotlela said that as a member of EU-M4all, SAHPRA would be allowed to participate in its lenacapavir evaluation by offering some of its own expertise for parts of the review.
“In essence, it will be a joint evaluation with the EMA – and certainly be faster than if SAHPRA did the review on its own.”
For example, SAHPRA took more than a year (from November 2021 to December 2022) to approve the monthly anti-HIV injection CAB-LA, containing the antiretroviral cabotegravir.
With EU-M4all, reviews take a maximum of seven months and regulators of participating countries then have three months to finalise the process locally.
Gilead will have to use its local branch to file for registration with SAHPRA, and in lenacapavir’s case, that can only be done once the EU-M4all review has been completed, because the approved evaluation data, prepared by EU-M4all, would have to be used.
The dossier contents will have to be slightly adjusted for the local application, to comply with SAHPRA’s regulations.
Gilead would need to pay the regulator R208 400 to work through its request, because it falls under the category of “a new chemical entity, new biotherapeutic other than vaccines” in the fee structure, said Semete-Makokotlela.
If the filing takes place after new fee structures have been gazetted, the price will be slightly higher.
So with which regulator is Gilead likely to file first?
Warren said the company would almost certainly prioritise the US Food and Drug Administration (FDA), which could approve lenacapavir in possibly six months.
“In addition, the hope is to see multiple countries having approved it by this time next year.”
Meanwhile, the National Department of Health’s head of procurement, Khadija Jamaloodien, told Bhekisisa the department was considering publishing a request for information – the formal way of asking manufacturers at which price they can provide a product and how much of it they can make – before SAHPRA’s approval has been concluded.
It would be an unprecedented move, to save time, similar to Gilead issuing licences to six generic companies in India (3), Egypt (1), Pakistan (1) and the US (1) in early October, before the company had applied for registration of lenacapavir with any regulators.
That way, generic companies can start to prepare to make the drug while registration applications are being processed and not lose that time – which could be months, and sometimes years.
“It’s still early days,” Jamaloodien said. “Let’s give those six generic companies some time to work out how they will approach us.”
To do this, however, the national essential medicines list committee, NEMLC, first has to study lenacapavir’s safety and efficacy data from trials and decide at what price the jab would be cost effective for South Africa.
The Health Department can only buy medicines that the NEMLC recommends should be added to the country’s shopping list, and tenders can only be issued once SAHPRA has registered the medicine.
Jamaloodien said the NEMLC had started its review for lenacapavir, but no details are available yet.
Price SA can pay for jabs
In July, the department published an RFI for the two-monthly anti-HIV jab (CAB-LA), of which generic versions are expected to go to market in 2027.
Jamaloodien had received “several responses” by the 9 September deadline, which the department is now studying. The outcome of the review will be made public between January and March 2025.
South Africa will receive 96 000 donated CAB-LA jabs from the US Government by December, and another 135 000 more during next year, which will be available free at 857 government clinics. However, the doses are enough to only cover 21 000 people over two years.
CAB-LA can slash the country’s new HIV infections by more than a quarter over 20 years, a modelling study shows. (Similar figures are not yet available for lenacapavir.)
But the outcome of the RFI and the fact that the Health Department would be starting people on CAB-LA with donations that, at least at this stage, will last for only two years, is no guarantee the country will issue a tender for CAB-LA.
“We don’t know if the market can bear both lenacapavir and CAB-LA,” said Warren. “I suspect it will all come down to price.”
For injectable PrEP to be affordable, the NEMLC compares the price to what a daily HIV prevention pill, available free in most state clinics, costs the government (R629.40 for a year’s medication for one patient).
A cost model, looking at the affordability of CAB-LA, shows for the jab to become widely available at state clinics, the shots should cost the same or at most double what the government pays to give someone two months’ prevention pills (two months, because CAB-LA is taken every second month).
From that reasoning, a lenacapavir jab should not cost more than R624.36 a shot – thus around R1 250 for a year of protection against HIV.
CAB-LA’s manufacturer, ViiV Healthcare, sells the jab at £23.50 per dose to donors and low- and middle-income countries like South Africa until cheaper generics become available, working out to just more than five times more than what the state pays for a two-month supply of the daily HIV prevention pill.
Gilead hasn’t announced the no-profit price at which it will sell its branded product to SA and other countries until generics become available, but Warren hopes it will be no more than $100 for a year’s supply per person.
But even at this price, he said it was only possible when vials for at least 1m users per year – so 4m jabs – are produced (users get two jabs per six-monthly visit).
A modelling study released earlier this year showed lenacapavir can be made for as little as $40 per year per patient, but only if 10m people take it up.
At this price, the study authors say, drug makers would still make a profit of 30%.
However, Warren warns that getting to such low prices will take time – and competition. And there would need to be guaranteed buyers, or drug makers won’t consider it worthwhile to make the medicine.
“Six generic companies will compete to sell their lenacapavir products, which will drive down prices, but they can only compete if there’s demand, so we need to create a market.”
See more from MedicalBrief archives:
Efficacy of six-monthly anti-HIV jab confirmed in second study
Gilead inks deal for generic HIV drug supply to low-income nations
Campaigners call for cheaper version of costly HIV drug