India must test new TB drug: Survivors appeal to Minister Harsh Vardhan

Pretomanid is the latest TB drug to get USFDA approval

Namita Kohli
Sept. 6, 2019, 10:29 a.m.

Tuberculosis activists have appealed to Union Health Minister Dr Harsh Vardhan requesting India to test a new TB drug, which has been approved by the USFDA.

'Survivors against TB'—a group of TB survivors and patient advocates—has written to the minister highlighting the need to “conduct research” on the Pretomanid-based regimen for treating drug resistant TB. The regimen includes Pretomanid, the latest drug to get USFDA approval and touted as a “lifesaver” for people with extensively drug-resistant tuberculosis. The USFDA approval, which came in August, makes the regimen a shorter treatment one.

According to Médecins Sans Frontières (MSF), an international humanitarian organisation that has been working on TB for 30 years, Pretomanid is the third new drug developed for TB in over half a century—the other two being delamanid and bedaquiline—and the first to be developed as part of a ready-to-use treatment regimen. The regimen is expected to benefit at least 12,000 patients of extremely drug-resistant TB.

The three-drug regimen (BPaL: bedaquiline + pretomanid + high-dose linezolid) has been approved for adult patients with XDR-TB, treatment-intolerant, or non-responsive multi-drug resistant pulmonary TB. MSF global spokespersons said the new regimen could “dramatically” shorten treatment period to six months, greatly reduce the number of pills required, and help to increase XDR-TB cure rates from the abysmal figure of 34 per cent.

Though shorter and simpler to administer, optimism around BPaL is also being balanced against the need for monitoring for side effects from the high doses of linezolid required. “The reduction of the treatment span from two years to a mere 6-8 months is exciting. However, we need to understand the complete side-effects of the proposed regimen,” the group 'Survivors against TB' said in a statement.

According to the USFDA, the most common adverse reactions observed in patients treated with pretomanid in combination with bedaquiline and linezolid included damage to the nerves (peripheral neuropathy), acne, anaemia, nausea, vomiting, headache, increased liver enzymes (transaminases and gamma-glutamyltransferase), indigestion (dyspepsia), rash, increased pancreatic enzymes (hyperamylasemia), visual impairment, low blood sugar (hypoglycemia), and diarrhoea. Pretomanid used in combination with bedaquiline and linezolid should not be used in patients with hypersensitivity to bedaquiline or linezolid.

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.

Besides the optimism around the shorter regimen, there's considerable hope that the new drug—developed by TB Alliance, a not-for-profit organisation, and funded by governments (Australia, Germany, the UK and the US) and philanthropic sources—would be affordable and accessible in countries such as India that have a high number of patients.

“Pretomanid should be made available at cost of under one dollar. Considering India's growing burden of DR-TB, India must lead the conversation around access and affordability. Dr-Tb is possibly the biggest area of spending in India's TB budget,” the group said in the statement. “Bedaquiline is still highly controlled, so the question of access to the new regimen remains crucial. We also need to ensure that the drug is affordable and long waiting periods are avoided,” they added.

In April this year, TB Alliance granted the first licence to the US pharmaceutical corporation Mylan to manufacture, register and supply pretomanid. According to MSF, 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 $0.36 and $1.14 per day. The lowest global prices for the other two drugs in the regimen, bedaquiline and linezolid, already run at around $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.

Harsh Vardhan has assured the group that the issue would be "examined", they said.


Source: The Week