Analysis: SA secures good prices for TB medicines, with one exception

In recent years South Africa has been a world leader in making new tuberculosis (TB) medicines available to people with drug-resistant forms of TB. South Africa was, amongst others, ahead of the World Health Organization in recommending in mid-2018 that hearing loss causing injections should be replaced with the still relatively new medicine bedaquiline when treating multi-drug resistant TB (MDR-TB).

South Africa has also generally been able to negotiate good prices for TB medicines when compared to other countries. This remains true with newly announced prices, although there is one puzzling exception.

Successful tenders and price negotiations for MDR-TB medicines are of particular importance given that some of the newer medicines used to treat drug-resistant forms of TB are still under patent and some of those that are off-patent have very few suppliers or only one. By contrast, the medicines used to treat drug-susceptible TB are all generic and very cheap.

As with ARVs, TB medicines are purchased by the state through a large tender – three years for HIV and two years for TB. The outcomes of the October 2019-September 2021 TB tender were recently announced. While most TB drugs are purchased through this tender, a few are purchased through the broader anti-infectives tender (see linezolid below).

Below we take a closer look at the tender prices of four of the five new TB drugs discovered and/or registered in the last three or so decades: bedaquiline, delamanid, linezolid and rifapentine. The fifth new TB drug, pretomanid, is not included in the tender since it has only just been approved by the United States Food and Drug Administration and important questions about its safety and efficacy remain unanswered.

The Rand/Dollar conversions below should be considered rough approximations given the relative instability in the exchange rate.

Bedaquiline

The tender price for a standard 24-week course of bedaquiline (188 100mg tablets) is R5 400 (around US$360). This averages out to around R32 per day (just over $2) for the first 24 weeks – although it should be kept in mind that the dose is much higher in the first two weeks than in the next 22 weeks and if the treatment period is extended beyond 24 weeks the average cost will accordingly decline.

The R32 a day price is just over double the R15 a day price that activists have recently been calling for.

South Africa’s tender price is slightly lower than the Global Drug Facility’s (GDF) listed price of $400 for a 24-week course. The GDF is a multinational procurement initiative that generally provides a good benchmark for the lowest international price of certain medicines.

Either way, with just over 30 000 six-month courses of bedaquiline being purchased for the next two years, all people in South Africa who need bedaquiline should be able to get it – which is more than what can be said for most other countries with high TB burdens.

According to Dr Norbert Ndjeka of the National Department of Health the intention is to treat 10 000 patients per year with regimens containing bedaquiline. He told Spotlight that an estimated 20 to 30% of patients will need to take the drug for more than 24 weeks (six months). He pointed out that even if 50% of patients need to take bedaquiline for 12 months the projected volumes will be enough.

Delamanid

A pack of 48 Delamanid 50mg tablets will be purchased for R1 410 (slightly less than US$100). The price per pack will drop to R1 200 in June 2020. With a standard dosage of 200mg per day taken for 24 weeks, a six-month course comprises 14 packs at a total price of around R19 800 per patient (around $1 330). This is significantly lower than the GDF list price of $1 700. Thus, while the tender price is high compared to other TB drugs, it compares well with a key international benchmark.

The tender price of delamanid works out to around R117 per day – well over three times the daily price of bedaquiline.

Government will be purchasing 84 000 packs of delamanid, which works out to 6 000 treatment courses over the two years of the tender (3 000 courses per year). The lower volumes compared to bedaquiline makes sense since fewer patients will be eligible to receive delamanid in terms of current treatment guidelines.

Ndjeka pointed out that the prices of both bedaquiline and delamanid have come down in recent years and indicated that he is satisfied with the tender prices for these two medicines.

Linezolid

One concerning thing is that the price of another important MDR-TB medicine called linezolid has gone up. Linezolid came off patent a few years ago. That, together with increasing volumes should in theory have led to a price reduction. The price paid by the Department of Health has instead gone up.

Linezolid is not purchased through South Africa’s TB medicines tender, but through the anti-infective medicines tender (which also runs from October 2019 to September 2021). This is likely because linezolid is not used exclusively for the treatment of TB.

The new tender price for a pack of ten 600mg linezolid tablets is R544 (around $37). The new product is being purchased from the pharmaceutical company Pfizer. Previously the Department procured essentially the same product from Teva Pharmaceuticals at the much lower price of R366 per pack. The GDF only lists packs of 100 tablets, but divided by 10 their lowest price for 10 tablets works out to a fraction of the South African tender price at around R66 ($4.42). The lowest private sector price in South Africa is over R5 400 for a pack of 10 tablets – ten times the tender price.

The tender price of a six-month course of linezolid works out to around R9 800 (roughly $660). The lowest GDF price is roughly one eighth of this at R1 200 (or $80) for six months.

The comparatively high tender price for linezolid and the fact that the price has increased is surprising given that the South African Health Products Regulatory Authority (SAHPRA) has registered oral linezolid products from eight  different suppliers and there should thus be competition in the market. After registering their linezolid product in 2002, Pfizer had the market to themselves until the first generic was approved in 2014. According to SAHPRA, Pfizer, Aspen Pharmacare, Specpharm, Zentiva, Abex Pharmaceutica, Ascendis Pharma, Innovata Pharmaceuticals and Teva Pharmaceuticals all have oral linezolid products registered in South Africa and 12 more applications are pending.

Ndjeka expressed concern over the increase in the price of oral linezolid and could not provide an explanation for the increase.

Drug	SA tender price (24-week course)	Lowest GDF price (24 weeks)
Bedaquiline	$360	$400
Delamanid	$1 330	$1 700
Linezolid	$660	$80

Note: There are important unanswered questions regarding the optimal dosing of linezolid. This obviously has implications for the price. Many patients also will not be able to complete six months of treatment at 600mg per day due to side effects.

Rifapentine

Finally, the tender includes the drug rifapentine. This inclusion is exciting since it may indicate a change in the way latent TB infection is treated in South Africa. Until now, we have been treating latent TB infection with the drug isoniazid, taken for anything from six to 36 months. While rifapentine can be used to treat drug-resistant TB, most excitement about the drug relates to its use for treating latent TB infection as part of the so-called 3HP regimen. 3HP involves treating latent TB infection with the combination of isoniazid and rifapentine taken once a week for three months.

The recommended dose of rifapentine in the 3HP regimen is 900mg once a week for 12 weeks. The tender includes packs of 24 150mg rifapentine tablets at a price of R244 per pack. People will need three packs at a total price of R732 (around $49). The GDF’s listed price for three packs is $45.

The volumes of rifapentine are however very low, suggesting that only a few hundred people will receive it – whether this will be in a pilot of the 3HP regimen, or potentially in the treatment of drug-resistant TB is unclear. While the Department of Health did provide comment on Spotlight’s questions relating to bedaquiline, delamanid and linezolid, they provided no answers to questions relating to rifapentine.

Note: Should you find any errors in our calculations, please feel free to point them out  by posting in the comments below.