The South African arm of Indian drug company Cipla has confirmed that a generic version of the two-monthly HIV prevention injection, CAB-LA (long-acting cabotegravir), will be made at its Benoni and Durban plants.
This follows an announcement in March by the developers of the branded version of the injection, ViiV Healthcare, and the Medicines Patent Pool (MPP), that sub-licences to produce the generic have been granted to three companies, including Cipla, which has local manufacturing plants.
At the time, Pharmaceuticals Made in SA (Pharmisa) chair Stavros Nicolaou criticised the MPP for failing to grant licences to African generic drug makers, MedicalBrief noted.
A starting date for manufacturing of the generic hasn’t been announced yet, writes Zano Kunene for Bhekisisa: the other two companies given licences are Indian corporations already producing antiretroviral drugs for HIV treatment – Auribindo and Viatris.
Cipla SA spokesperson Fidelia van der Linde said it’s unclear whether they will make the generic version of CAB-LA from scratch or import the main ingredient and then only mix and bottle it in South Africa.
“However, most pharma companies in South Africa import their active (main) pharmaceutical ingredients.”
The final packaging of a pharmaceutical product like CAB-LA is, though, still a complicated process and new technology that would have to be set up, said Van der Linde.
Under the licence agreements, the generics companies will get ViiV’s CAB-LA recipe, as well as information on how to apply the recipe (called technology transfer).
The branded version of CAB-LA sells for about R67 000 a pop in the US and is out of reach for lower-income countries.
Even at a lower, “not-for-profit” price at which the manufacturer said it will sell the medicine to 90 poorer countries, including South Africa, the brand-name shot is likely to be too expensive for the government to buy.
Although not confirmed, it could be about R4 600 a person a year (so, R767 an injection), said Mitchell Warren, executive director of the Aids Vaccine Advocacy Coalition (Avac), which is involved in the price negotiations.
As orders grow, Mitchell said, the price could drop to below R3 700 a year.
But even the “large-order” price might be more than double what a modelling study published in Lancet HIV has shown would be sensible for South Africa to pay.
Researchers calculated that for CAB-LA to be cost effective for SA, the Health Department shouldn’t fork out more than double what they would have paid for two months’ supply of the daily HIV prevention pill per patient.
A month’s pills per patient costs the government R60. This is for the tablet only and doesn’t include admin fees such as health workers’ time, and transport costs. So, according to the study, the public health sector shouldn’t pay more than R240 (twice what the pills cost) per two-monthly shot.
In December, Khadija Jamaloodien, the Health Department’s director of affordable medicine, said that if a budget assessment – due to be completed by the end of March – showed the government could afford branded CAB-LA, it would take about six months before the jabs can be rolled out.
Having generic versions of a drug available means, in theory, that roll-out could be cheaper and faster. But being granted a licence to produce a generic version of a branded medicine is only the first step in getting cheaper options to people.
The deal is a reminder of how important intellectual property agreements and tech transfer are to get medicines to people who need them most, said Esteban Burrone, head of policy at the MPP.
1. More competitors mean lower drug prices
Medicines are protected by patents, which usually last for 20 years. This means a single company holds exclusive rights to manufacture and sell a product without competition in a country. It often leads to medicines being expensive, and out of reach for many people.
ViiV Healthcare holds the patent for CAB-LA until 2031.
But given licence agreements like the one with Cipla, more than one manufacturer can enter the market. Competition is good for consumers because companies are likely to drop their prices, said Burrone. Without licences granted to other pharmaceutical companies to make generics, ViiV wouldn’t have had any competition for buyers for at least another eight years.
2. More producers mean more people can get new medicines, faster
When there are more manufacturers producing a drug, there’s also enough to go around. And at a cheaper price, governments in poorer nations are more likely to buy it.
3. Intellectual property deals reduce drug shortages
They can also lessen the effect of medicine shortages, because alternative suppliers would be available should a company run out of stock. But when there’s no such agreement, things can become dire in poorer countries.
Licence agreements for generics don’t completely remove the risk of short supplies, though, warmed Burrone.
The lower price at which generics are sold means profit margins might not be as high as with branded medicines. Manufacturers may therefore not want to make the products and so a shortage of generics could still develop.
For this reason, manufacturers who want a sub-licence have to agree that they will do their best to produce “broad access to the product” as soon as they are awarded manufacturing rights. For CAB-LA, Burrone said they “zoomed in on the three manufacturers who are most ready” to address the existing demand.
4. Public health wins when there are manufacturers in different regions
Less than 40% of the medicines Africa needs can be made on the continent, and it’s estimated that only 38 countries have any drug makers. Where they do exist, the companies rarely make medicines from scratch.
When already-made and packaged medicines are imported, they can be pricey. It’s cheaper to import raw materials to make the medicine locally than to ship in a finished product.
For example, in Ethiopia, to import a finished over-the-counter medicine from India would cost 12% more than to make it locally from scratch.
Moreover, the imported product’s price would include a 20% mark-up to cover the cost of getting it to the distributor, which is much higher than if the medicine was made locally.
But to get these benefits, Burrone said the original developers would need to agree to offer tech transfer as part of the licence agreements so that generics companies can expand the expertise to manufacture drugs with complex recipes locally.
Study details
Relative cost-effectiveness of long-acting injectable cabotegravir versus oral pre-exposure prophylaxis in South Africa based on the HPTN 083 and HPTN 084 trials: a modelled economic evaluation and threshold analysis
Lise Jamieson, Leigh Johnson, Brooke Nichols, Sinead Delany-Moretlwe, Mina Hosseinipour, Colin Russell, et al
Published in The Lancet HIV on 7 November 2022
Summary
Background
Long-acting injectable cabotegravir, a drug taken every two months, has been shown to be more effective at preventing HIV infection than daily oral tenofovir disoproxil fumarate and emtricitabine, but its cost-effectiveness in a high-prevalence setting is not known. We aimed to estimate the incremental cost-effectiveness of long-acting injectable cabotegravir compared with tenofovir disoproxil fumarate and emtricitabine in South Africa, using methods standard to government planning, and to determine the threshold price at which long-acting injectable cabotegravir is as cost-effective as tenofovir disoproxil fumarate and emtricitabine.
Methods
In this modelled economic evaluation and threshold analysis, we updated a deterministic model of the South African HIV epidemic with data from the HPTN 083 and HPTN 084 trials to evaluate the effect of tenofovir disoproxil fumarate and emtricitabine and long-acting injectable cabotegravir provision to heterosexual adolescents and young women and men aged 15–24 years, female sex workers, and men who have sex with men. We estimated the average intervention cost, in 2021 US$, using ingredients-based costing, and modelled the cost-effectiveness of two coverage scenarios (medium or high, assuming higher uptake of long-acting injectable cabotegravir than tenofovir disoproxil fumarate and emtricitabine throughout) and, for long-acting injectable cabotegravir, two duration subscenarios (minimum: same pre-exposure prophylaxis duration as for tenofovir disoproxil fumarate and emtricitabine; maximum: longer duration than tenofovir disoproxil fumarate and emtricitabine) over 2022–41.
Findings
Across long-acting injectable cabotegravir scenarios, 15–28% more new HIV infections were averted compared with the baseline scenario (current tenofovir disoproxil fumarate and emtricitabine roll-out). In scenarios with increased coverage with oral tenofovir disoproxil fumarate and emtricitabine, 4–8% more new HIV infections were averted compared with the baseline scenario. If long-acting injectable cabotegravir drug costs were equal to those of tenofovir disoproxil fumarate and emtricitabine for the same 2-month period, the incremental cost of long-acting injectable cabotegravir to the HIV programme was higher than that of tenofovir disoproxil fumarate and emtricitabine (5–10% vs 2–4%) due to higher assumed uptake of long-acting injectable cabotegravir. The cost per infection averted was $6053–6610 (tenofovir disoproxil fumarate and emtricitabine) and $4471–6785 (long-acting injectable cabotegravir). The cost per long-acting cabotegravir injection needed to be less than twice that of a 2-month supply of tenofovir disoproxil fumarate and emtricitabine to remain as cost-effective, with threshold prices ranging between $9·03 per injection (high coverage; maximum duration) and $14·47 per injection (medium coverage; minimum duration).
Interpretation
Long-acting injectable cabotegravir could potentially substantially change HIV prevention. However, for its implementation to be financially feasible across low-income and middle-income countries with high HIV incidence, long-acting injectable cabotegravir must be reasonably priced.
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Generics green-light for new HIV drug, but Africa peeved
HIV game-change with SAHPRA approval and vaccine trial breakthrough
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