From paper to provinces: Find out how far South African provinces have come in implementing the country's national HIV and TB plan. (Vladimir Konstantinov)
South Africa’s medicines regulator confirmed on 2 December that it has registered drugmaker ViiV Healthcare’s HIV prevention jab, CAB-LA, for “people at substantial risk of HIV infection”. This comes after ViiV issued a statement on Thursday.
The chief executive of the South African Health Products Regulatory Authority (Sahpra), Boitumelo Semete-Makokotlela, said CAB-LA is authorised for use in people who weigh 35kg or more. It is not indicated for use in pregnant women, as “safety has not yet been sufficiently demonstrated in pregnant women”.
The injection has also been approved in other countries such as the United States, Australia and Zimbabwe.
It is taken every two months and consists of a long-acting version of an antiretroviral drug, cabotegravir, which blocks HIV from entering someone’s cells. Studies have shown that it virtually eliminates someone’s chances to contract HIV through sex and works better than a daily HIV prevention pill that’s available for free in South Africa — most likely because it’s easier to take it regularly.
CAB-LA will be sold in South Africa under the brand name Apretude, but whether the health department buys it will depend on the price at which ViiV Healthcare is prepared to sell it to the government.
The National Essential Medicines List Committee, a group of experts appointed by the health minister to advise him about medicines, will now conduct a budget assessment, which will take two to three months.
The jab is sold in the US at R54 000 a pop. According to a modelling study published in The Lancet HIV this month, that’s 200 times more than what would be sensible for South Africa to pay.
The researchers calculated that for CAB-LA to be cost-effective for South Africa, the health department shouldn’t fork out more than double what they pay for the daily HIV prevention pill, which works out to about R240 per injection.
Cheaper, generic versions of CAB-LA will only be available in three to five years; ViiV Healthcare has therefore offered to sell their branded product at a much-reduced, “not-for-profit” price to 90 poorer countries — including South Africa — until generic products are on the market.
But the drugmaker hasn’t yet announced what this price would be, and the fee will depend on how many orders donors and governments can commit to, as production at scale will lower costs.
So what happens now? Mia Malan asked the head of research and development at ViiV Healthcare for Bheksisa’s television programme, Health Beat. Kimberly Smith led the scientific development of CAB-LA.
Mia Malan (MM): Access to CAB-LA in Africa will largely depend on the price at which ViiV sells it to poorer countries. Have you decided on a price?
Kimberly Smith (KS): We’ve repeatedly said that we’ll make it available at a non-for-profit price. We’re doing everything we can through partnerships to make that price as low as possible. I can’t give you a number.
MM: How much longer will the price negotiations take?
KS: The goal is to get the price as low as possible. Some of that depends on volume guarantees. CAB-LA is a sterile injectable product. It’s a very, very complex manufacturing process. Instances where it’s been compared to the manufacturing cost of a simple white pill is unrealistic.
MM: What is the minimum size of the order that ViiV needs to be able to make it viable to produce CAB-LA at an affordable price?
KS: I can’t give that number to you. I can say that the partnerships that we have with groups like [the] Bill and Melinda Gates Foundation, and CIFF [Children’s Investment Fund Foundation] and Unitaid are critically important for helping to understand what the demand and volume requirements will be in both the early years and when demand ramps up over time. The volumes will increase over time and that will allow for improvements in the price.
MM: Scientists and activists with whom we’ve spoken say the price will be around £35 per jab and the amount will then eventually be cut in half as demand increases. Are you looking at prices in that range when you talk to donors?
KS: I don’t want to get into specifics about the price. Part of the challenge around specifics is that it has the potential to dissuade some of the generic companies that are interested in coming in. If we start quoting prices, we’ll end up having to change them over time. A lot of numbers are floating around; for the most part, they’re inaccurate, because they don’t fully take into account some of the complexities such as what will happen with regard to the volume.
MM: Once you’ve agreed on a price, how long will it take for ViiV to manufacture at a large scale — how far along are you with developing that capacity with regards to CAB-LA?
KS: We’ve been working with our manufacturing partners and GlaxoSmithKline to do everything possible to maximise our capabilities. We hope this matches demand. We’ll need to understand more about what the demand will be in the short term, in the 2023 to 2025 time frame.
MM: Do you know what ViiV’s maximum manufacturing capacity for CAB-LA is, say, annually?
KS: That’s changing as we optimise our manufacturing capabilities. I don’t want to commit to what we can deliver.
MM: Has ViiV had discussions with the South African government with regards to price?
KS: There are no negotiations with the South African government, as far as I understand, at this point.
MM: One of the challenges with creating a market for HIV prevention is to get healthy people to clinics for jabs. What do clinical trials tell us about adherence — do people return to clinics every two months?
KS: Clinical trials showed us that people were tremendously adherent. That led to a tremendous outcome, where CAB-LA was three times more effective [than the daily HIV prevention pill] among men who had sex with men and transgender women and nine times more effective in cisgender women. That’s an indication that people definitely did show up on time. Obviously, there’s some flexibility — we have a little bit of a window around the dosing that allows for flexibility; you’d have a week before or after that exact date when you’re scheduled to return.
MM: Have you seen any signs that this might be different for real-world circumstances, for instance the case of the United States’ roll-out?
KS: We’ve only been on the market for a year in the US. We haven’t seen any difference from what we saw in the clinical trials thus far, but it’s still fairly early. The long and short of it is that we saw high adherence rates in clinical trials. Coming in every two months was a relatively small price to pay for that kind of satisfaction and the freedom that participants felt from not having to worry about taking a pill every day.
MM: One way to get women to clinics is to offer them CAB-LA when they visit clinics for contraception. But in South Africa, the most common form of contraception is a three-monthly jab. Are you looking into whether CAB-LA can be given every three, instead of every two months?
KS: Yes. Part of the 084 study for cisgender women took place during some of the worst times of COVID in South Africa, so we allowed for some flexibility. If they needed to, women could come in every three months when it was difficult to get to a clinic. That happened to roughly 200 women and we didn’t see any negative consequences. We’re doing more work on this and will share data at the Conference on Retroviruses and Opportunistic Infections early next year.
MM: One of the concerns with CAB-LA is that cabotegravir falls into the same drug class (integrase inhibitors) as dolutegravir, an antiretroviral that most people with HIV in Africa use. Are you concerned that people who take CAB-LA and do get infected will have built up resistance to dolutegravir?
KS: Infections have occurred, but very rarely. It’s something to recognise as a potential risk, but from the clinical trials that occurred very, very rarely.
MM: What are the most common side effects of the jab?
KS: Pain at the injection site is fairly common in the beginning, but it tends to decrease over time — either people get better at giving the injections or people who are getting the injections get used to it. Discontinuation as a result of injection site reactions was extremely rare in clinical trials.
MM: Do you think this injection will be a game changer?
KS: I absolutely believe that. We have not seen a product to have this level of efficacy in the past. This has the potential to change the trajectory of the HIV pandemic.
This story was produced by the Bhekisisa Centre for Health Journalism. Sign up for the newsletter.