GENEVA/NEW YORK – Doctors Without Borders/Médecins Sans Frontières (MSF) welcomes the approval by the US Food and Drug Administration (FDA) of a combination regimen containing a new drug, pretomanid, for the treatment of extensively drug-resistant tuberculosis (XDR-TB).
As the third new drug developed for TB in over half a century, and the first to be developed as part of a ready-to-use treatment regimen, pretomanid’s approval represents another potent tool for tackling difficult-to-treat drug-resistant forms of TB.
The drug must be made affordable to everyone who needs it, especially considering the substantial taxpayer and philanthropic contributions that went into its development.
The three-drug regimen (BPaL: bedaquiline + pretomanid + high-dose linezolid) was approved for adult patients with XDR, treatment-intolerant, or non-responsive multidrug-resistant pulmonary TB. The new regimen could dramatically shorten treatment length to six months, greatly reduce the number of pills required, and help to increase XDR-TB cure rates from the abysmal historical figure of 34 per cent.
While the new regimen will be shorter and simpler to administer, optimism around BPaL is balanced against the need for intensive monitoring for side effects from the high doses of linezolid required.
Separate clinical trials run by MSF and TB Alliance are underway to further evaluate pretomanid-containing regimens to try to identify safer future treatment options.
“The treatment of XDR-TB has been dire ever since this form of the disease was discovered,” said Jay Achar, infectious disease specialist and TB medical advisor at MSF. “Having access to effective treatment regimens will give people hope of a cure, and help programmes limit transmission of this deadly bacteria. While safer, simpler regimens are still needed, the shorter treatment duration of this novel regimen is an important step in the right direction.”
Pretomanid was developed by TB Alliance, a not-for-profit organisation, funded by governments (e.g. Australia, Germany, the UK and the US) and philanthropic sources, with the expectation that the organisation would hold true to its stated mission, that they are “dedicated to the discovery, development and delivery of better, faster-acting and affordable tuberculosis drugs that are available to those who need them.”
In addition, TB Alliance stands to be granted a tropical disease priority review voucher (PRV)*, which it can sell for a substantial amount: PRVs have previously been sold for US$67-350 million.
MSF calls for TB Alliance to use this financial reward to ensure that the drug gets registered and made available at an affordable price, fast.
“This newly approved regimen containing pretomanid could be a lifesaver for people with XDR-TB, but it’s not time to celebrate yet,” said Sharonann Lynch, HIV & TB policy advisor for MSF’s Access Campaign. “The approval of this new regimen by the US FDA is just the first step. We now need pretomanid to be registered and available at an affordable price in all countries, prioritising those with the highest TB burden.”
In April this year, TB Alliance granted the first license to the US pharmaceutical corporation Mylan to manufacture, register and supply pretomanid.
To date, TB Alliance and Mylan have not made the price of pretomanid public. It has been estimated that generic versions of pretomanid could be produced and sold at a profit for between US$0.36 and US$1.14 per day.
The lowest global prices for the other two drugs in the regimen, bedaquiline and linezolid, already run at around US$3 per day; people needing this treatment regimen would have to take it for six months, amounting to a total price of US$548, before considering the additional price of pretomanid.
MSF has called for treatment of drug-resistant TB to be no higher than US$500 per person for a complete treatment course.
But four months on, neither Mylan nor TB Alliance has made the licensing agreement public, despite calls from civil society for transparency on the terms and conditions that will ultimately impact people’s access to this drug globally.
Mylan is expected to bring pretomanid to market by January 2020. However, this is dependent on World Health Organization guidance on using the drug, and on Mylan filing for registration in countries with the highest DR-TB burden.
“TB Alliance and Mylan must not squander this opportunity. They must make good on TB Alliance’s mandate to deliver affordable treatment – which is why they received the support of government and philanthropic funding that went into the development of pretomanid and this combination – and provide the drug at an affordable price because when it comes to people with resistant forms of TB, it’s a matter of life or death,” said Lynch.
