Lenacapavir — what it would it take to get the six-monthly anti-HIV jab to South Africa

Yvette Raphael and her daughter Yisha. (Photo: Supplied)

By Mia Malan and Linda Pretorius

31 Jul 2024

Speed, scale and price would sway whether drugmaker Gilead’s twice-a-year anti-HIV jab, lenacapavir, will be able to markedly slow down new infections in South Africa and the world. What needs to happen for South Africa to get the jab? Find out.

The shot was tested on teen girls and young women between the ages of 16 and 25 in South Africa and Uganda and made world headlines in June, and also at the recent International Aids Conference in Munich, when results showed not one of the 2,134 study participants who received the six-monthly injection contracted HIV.

Young women in South Africa are contracting HIV much faster than anyone else – 122 of them get infected with the virus each day – figures from the country’s Thembisa model, which the Health Department uses to plan its programmes, shows.

As a result, four out of every 10 new infections in the country are in this group, even though they make up only about 8% of the total population.

Lenacapavir works by stopping HIV from making more copies of itself and so getting into someone’s immune cells.

But translating trial results into something that works in real life in countries like South Africa is often considerably harder than developing the actual medicine, says Mitchell Warren, who heads up the New York-based advocacy organisation Avac.

“It’s going to take policymakers, funders and communities getting together to decide we want to get to zero in real life.”

For HIV infections to fall, South Africa would need tens of millions of doses

Research shows that a marked drop in HIV infections in a community is seen only if HIV prevention medication reaches a lot of people. For example, in places where the incidence rate (the rate at which people are getting infected) is 3% or more, 33 people need to take prevention medication to stop one new infection (some areas in southern Africa have high incidence rates like this). In places where the chance for new infections is lower, 200 people have to take HIV prevention drugs to stop one new infection.

So, to slow down new HIV infections enough to really get us close to reaching the goal of ending Aids as a public health threat by 2030, South Africa would need tens of millions of lenacapavir doses – and soon.

The good news is that data from the Health Sciences Research Council’s 2022 household survey, released at the conference, reveals that people in South Africa are open to using pre-exposure prophylaxis (PrEP) which can prevent infection.

Almost two-thirds of people who had heard of PrEP said they were willing to take the medication to protect themselves against HIV. But the catch is that only one in three people who took part in the study had ever heard of PrEP.

And to convince people to use PrEP, they needed to have heard of it.

Warren explains: “People aren’t magically going to wake up in South Africa, or any other country, and say they want lenacapavir. We have to create demand for prevention, and to build programmes that deliver what people want, when they want it, where they want it.”

Creating demand for an anti-HIV pill, which is also called oral PrEP and stocked in most government clinics, has been tricky – and the uptake therefore low.

The Health Department launched the tablet in 2016 – eight years later, by the end of April 2024, only 1.5 million people had taken a pill at least once; far fewer than the department had hoped for.

Oral PrEP has shown us, says Warren, that just because there’s a product that can stop people from contracting HIV, doesn’t mean anyone will use it. “People need to know about it, they need to know how it works, whether it would work for them and if it would fit their lifestyle.”

Generic versions of another anti-HIV jab, CAB-LA, which is taken once every two months, are expected to become available on a large scale only towards 2027, six years after results showing that it works were published. (The drug, which was registered by the South African Health Products Regulatory Authority, Sahpra, in 2022, will be rolled out in South Africa, albeit on a very small scale, towards the end of this year following a US donation.)

Says Warren: “History is going to judge us harshly if we squander lenacapavir – because we squandered cabotegravir [and] we squandered oral PrEP. Let’s hope we don’t squander lenacapavir, because I don’t know that we’re going to have many more chances.”

How much can South Africa pay for lenacapavir?

For injectable PrEP to be affordable for South Africa, the Health Department’s national essential medicines list committee compares the price to what the daily HIV prevention pill costs the government (R774 for a year’s medication for one patient).

A cost model, which looked at the affordability of CAB-LA (it’s taken every other month), shows that 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.

From that reasoning, a lenacapavir jab should not cost more than R774 a shot – about R1,500 for a year.

The department’s head of procurement says this price is a reasonable assumption, “but we will need to formally evaluate lenacapavir, which may have different input”.

The price is, however, almost 500 times less than what it’s sold for when used as a treatment for drug-resistant HIV infection at the moment in rich countries such as the US, Canada and some European countries.

In these countries, lenacapavir, which is used at the same doses and time intervals for treatment as for prevention, sells for between $40,000 and $44,000 (R740,000 to R814,000 at the current exchange rate) for a year’s supply.

But because it’s a niche treatment and therefore made in small amounts, it’s extremely expensive.

And that’s where scale comes in.

The more we make, the cheaper the meds will get – but only if there are buyers

A study released at the Munich conference shows lenacapavir can be made for as little as $40 (R740) per year per patient – but only if 10 million people take it up. If one million choose the medicine in a year, it can be made for $100 (R1,850) per person.

At these prices, the study authors say, Gilead would still make a profit of 30%.

But Warren says getting to such low prices will take time – and competition. And there would need to be guaranteed buyers, or drugmakers won’t consider it worthwhile to make the medicine.

“It’s not going to happen overnight with a brand-new product. Remember, these are sterile injections. They are manufactured very differently than pills and currently in very small quantities.”

One of the reasons the HIV prevention pill is so much cheaper than, for instance, the CAB-LA injection, is because the pill’s ingredients – tenofovir and emtricitabine – are used for entry-level treatment for people with HIV around the world. Hundreds of millions of doses are therefore produced each year, which brings down the price (close to 31 million people were on treatment by 2023; all people on standard first-line treatment need to take at least one daily pill containing three medications, two of which are tenofovir and emtricitabine).

There are also many different companies making generic versions of tenofovir and emtricitabine, so there’s competition in the market, and this also drives down prices.

Says Warren: “That’s what we need to build towards with newer prevention products: large volumes and multiple manufacturers. But if there’s large-scale product availability and no procurement by governments and donor agencies, the price isn’t going to drop.”

Will lenacapavir be made in Africa?

Governments and donors therefore need to publicly commit that they will buy jabs like lenacapavir – if the price is right.

Warren says the world can learn a lot from how we got millions of people with HIV onto affordable treatment.

“It’s because donors and governments made commitments, because we created supply chains, programmes and peer support groups – people came together to make big, important decisions.”

And to create competition in the market for lenacapavir, there needs to be companies that make cheaper, generic versions.

Shortly after the release of the Purpose 1 trial results for lenacapavir at the end of June, Gilead announced it would issue voluntary licences that will allow companies to do this. This means they’d share lenacapavir’s recipe, and how to put together the medicine’s ingredients, in exchange for a licensing fee.

But Gilead has not yet revealed which companies are being considered and from which countries. At a press conference in Munich, Bhekisisa asked Gilead’s senior vice-president of HIV clinical development, Jared Baeten, if the company would consider giving a licence to an African company.

But all he was prepared to reveal was: “We are moving with urgency to negotiate these contracts. When the agreements are finalised, you’ll have the list. There’s no long list yet.”

The way Gilead plans to issue voluntary licences is, however, controversial. The Joint United Nations Programme on HIV and Aids (UNAids), and also activists, want the drugmaker to issue licences through a UN-backed organisation, the Medicines Patent Pool (MPP).

When companies go through the MPP, the licence agreements are published on their website and so everyone can see what the conditions of a manufacturing deal is.

But when licences are issued directly, very little of this information is revealed. And transparency is what will hold Gilead accountable to issue fair licences, Winnie Byanyima, who heads up UNAids, said in Munich. “We want to recognise that these companies [such as Gilead] need to make a profit. But we want them to be transparent about their costs so that we know what profit they’re going to make.”

Baeten, however, says Gilead thinks it’s faster to do direct licensing because the company has established relationships with generic companies to which they have previously issued licensing agreements for other products.

How long will it take to get lenacapavir registered for use in South Africa?

Generic licensing is one thing – but of no value to health programmes if a drug isn’t registered with countries’ medicines regulators.

Only Gilead, as the original developer of the product, can file for registration – and it would need to apply separately in each country, which can take years.

Gilead, however, plans to use faster ways, it says, including World Health Organization approval procedures and a system called EU Medicines for All, which runs at the same time as the European Medicine Agency’s approval process (to save time). This can help other countries speed up their own checks because they can rely on already scrutinised data.

Sahpra’s CEO, Boitumelo Semete-Makokotlela, says South Africa is a member of EU-M4all, but even with this process, she says, it still can still take up to 210 days – seven months – for a product to be approved and another 90 days for each country to finalise the process on a local level.

“But it does save time, and when a pharmaceutical company needs to fill out the dossier that we send them, the time this takes is reduced from months to weeks, because they’re able to use the data they used for EU-M4all filing with only a few minor modifications,” she explains.

Gilead, however, says it will wait for the data from a second lenacapavir study, which will only be released by the end of the year or early next year before it files for registration with the EMA.

The second study tests lenacapavir on gay and bisexual men and transgender people.

Baeten says this will be a smoother process than filing for registration immediately, because it will allow for approval of a broader population straight away.

But Andrew Hill, a pharmacology expert who’s been working on the development of antiretrovirals for the past 30 years and who’s also the main author of the study on the cost of lenacapavir, presented at the conference, says this doesn’t make sense. “Rolling applications, which almost all regulators have, will allow Gilead to file now and then just add the new information later.”

Amid all this politics, about 43,000 young women in South Africa will get infected with HIV in 2024, figures from the Thembisa model show.

And to mothers like Yvette Raphael, who attended the Munich conference, which is held every two years, that is devastating.

HIV lenacapavir Yvette Raphael and her daughter Yisha. (Photo: Supplied)

“I took my daughter, Yisha, who is 24, with me. She’s HIV negative.

“I was 25 when I was diagnosed with HIV two decades ago. I don’t want Yisha to return to the next conference in 2026, or the one in 2028, and be HIV positive. That’s why I’m fighting for this medication to be affordable and widely accessible.” DM

This story was produced by the Bhekisisa Centre for Health Journalism. Sign up for the newsletter.

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For HIV infections to fall, South Africa would need tens of millions of doses