Mylan Gets Expert Panel Go-Ahead For Pretomanid In India
Executive Summary
Tuberculosis drug pretomanid gets endorsement, with Phase III trial waiver, from a key expert panel that advises India's drugs regulator, but roll out plan needs to be defined under the country’s national TB program, say health activists.
An expert panel that advises the Indian drugs regulator has cleared Mylan NV’s proposal for pretomanid subject to certain restrictions, though the new treatment for drug-resistant tuberculosis (DR-TB) appears to have been endorsed with a Phase III trial waiver.
The subject expert committee’s (SEC) go-ahead is significant since in September last year it opined that “data was not sufficient enough” to grant a clinical trial waiver for the drug in India. The panel now appears to have reviewed its position after the US firm provided its “justification” for the proposal to manufacture and market the product with such a waiver.
The SEC (antimicrobial and antiviral), in its recent meeting, maintained that there is an unmet need for the drug in patients with extensively drug-resistant TB (XDR TB) and noted that the use of pretomanid in combination with bedaquiline and linezolid is “reported to be advantageous” in respect of reduction of duration of treatment from 20 to six months.
“However, the drug should be used under restricted condition to prevent its misuse and development of resistance etc,” the SEC stressed.
The SEC went on to recommend the grant of permission to manufacture pretomanid to be used “only as conditional access” under India’s National TB Elimination Programme (NTEP) and subject to the condition that a Phase IV clinical trial be conducted under the program. India’s Revised National Tuberculosis Control Programme (RNTCP) was reported to have recently been renamed as the NTEP in line with the country’s ambitious goal of eliminating the disease by 2025.
In general, under India’s trial regulations, the requirements of non-clinical and clinical data may be “relaxed, abbreviated, omitted or deferred” in the case of life-threatening or serious disease conditions or rare diseases, and for drugs intended to be used in diseases of “special relevance” to the Indian scenario or for unmet medical needs in the country, or for disaster or special defense, among other scenarios.
Pretomanid was approved in combination with Johnson & Johnson’s Sirturo (bedaquiline) and Pfizer Inc.’s Zyvox (linezolid) by the US FDA in August 2019 for treating adult patients with XDR TB and treatment-intolerant or non-responsive multi-drug resistant pulmonary TB. (Also see "Pretomanid Approval For Resistant TB: With Regulatory Flexibility Comes Usage Restrictions" - Pink Sheet, 15 Aug, 2019.)
TB Program Has To Set Criteria
However, there is limited clarity on how soon pretomanid could become available on the TB program in India, at least for now. Mylan acknowledged the SEC’s latest recommendation but provided no specific comments on the endorsement by the expert panel or plans to roll out the new therapy.
Pro-health activists tracking the developments said told Scrip that the RNTCP has to now define “how it is going to provide the regimen and to whom,” claiming that there is also “practically no experience even under compassionate use of the new regimen in India.”
“The issue here is how is the government going to introduce and monitor the drug. This is a new regimen containing a new drug. The TB program has to set criteria and it cannot just be rolled out,” the activists told Scrip, adding that the RNTCP has not yet issued guidelines pertaining to the new regimen that includes pretomanid.
Pretomanid Collaborations
Pretomanid was developed by the TB Alliance, which in April 2019 struck a collaboration with Mylan to make the drug accessible for use in specific TB treatment regimens. Mylan is to commercialize the treatment for use in the BPaL (bedaquiline, pretomanid and linezolid) regimen in certain low- and middle-income countries, where the vast majority of the global TB burden is located.
The US firm will also commercialize pretomanid for use in the BPaL and BPaMZ (bedaquiline, pretomanid, moxifloxacin and pyrazinamide) regimens in high-income markets. In October last year, the TB Alliance also granted a non-exclusive license to the Indian firm [Macleods Pharmaceuticals Ltd.] for the drug. (Also see "Big Pharma Advances Efforts In TB But Pricing Stays Key Concern" - Scrip, 6 Nov, 2019.)
The Stop TB Partnership’s Global Drug Facility (GDF) then announced a global access price of $364 for a six-month treatment course of pretomanid available to 150 countries and territories, putting the cost of the FDA-approved BPaL regimen at $1,040 per treatment course (when bought from GDF at access prices). The humanitarian group Médecins Sans Frontières argued at the time that the GDF’s price of $364 for a six-month treatment course of pretomanid was too high and said a complete DR-TB treatment course should be available at no higher than $500 per person.
In January this year, the TB Alliance granted China's Shenyang Hongqi Pharmaceuticals Co. Ltd., an arm of Shanghai Fosun Pharmaceutical Group Co. Ltd., a license to market pretomanid as part of the BPaL regimen in China.