Hope For Price Flexibility After India Pretomanid Go-Ahead
Executive Summary
Mylan gets approval in India for pretomanid as part of a combination regimen with bedaquiline and linezolid, providing new hope to patients with drug-resistant tuberculosis. Volume changes may provide opportunities to tweak prices.
Mylan N.V. has received regulatory clearance for pretomanid in India, improving the prospects of expanded access to the new treatment for drug-resistant tuberculosis, amid disturbing signals that the world’s most deadly infection may rebound sharply while healthcare systems are currently burdened with treating COVID-19.
Pretomanid, developed by the non-profit organization TB Alliance, has been given the go-ahead by the Drugs Controller General of India for conditional access under the National Tuberculosis Elimination Program (NTEP).
Pretomanid was approved in combination with Johnson & Johnson’s Sirturo (bedaquiline) and Pfizer Inc.’s Zyvox (linezolid) - a regimen collectively referred to as “BPaL” - by the US FDA in August 2019 for the treatment of adults with pulmonary extensively drug-resistant (XDR), treatment-intolerant or non-responsive multidrug-resistant (MDR) tuberculosis. (Also see "Pretomanid Approval For Resistant TB: With Regulatory Flexibility Comes Usage Restrictions" - Pink Sheet, 15 Aug, 2019.)
Earlier this month the compound was granted conditional marketing authorization by the European Commission for treating highly drug-resistant forms of pulmonary tuberculosis. (Also see "New EU Approvals" - Pink Sheet, 4 Aug, 2020.)
Pretomanid, which appears to have been endorsed with a Phase III trial waiver in India, has been approved as part of the BPaL, six-month all-oral regimen, with an option to extend treatment to nine months in certain conditions. An expert panel that advises the Indian drugs regulator had earlier recommend the grant of permission for pretomanid to be used “only as conditional access” under the NTEP and subject to the condition that a Phase IV clinical trial be conducted under the program.
Specifics around the Phase IV study are not clear, though Mylan’s president, India and emerging markets, Rakesh Bamzai, told Scrip that the company is working closely with the NTEP on developing the “most suitable approach for generating real world evidence on pretomanid.”
In April last year, the TB Alliance 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 regimen in certain low- and middle-income countries, where the bulk of the global TB burden is located.
Effective Procurement
Meanwhile, pro-health groups have indicated that beyond the registration of protomanid, details of its roll out as part of the BPaL regimen under the NTEP have not been specified yet. The program typically updates the Programmatic Management of Drug Resistant TB (PMDT) guidelines each year.
“How BPaL will be integrated into the PMDT will then depend on the updated guidelines in 2020,” Leena Menghaney, Regional Head (South Asia) of the Access Campaign at Médecins Sans Frontières (MSF), told Scrip.
Menghaney also referred to the potential side-effects of the high dose of linezolid, indicating that clinicians may want to reduce the dose of the drug and add another TB drug. It’s unclear if such flexibility will be allowed to clinicians, she said.
Mylan explained that the World Health Organization recommends the use of pretomanid in combination with bedaquiline and linezolid for managing XDR TB under operational research settings. “The approved label in India, however, specifies the information needed to use pretomanid tablets safely and effectively. NTEP is expected to release the guidelines soon,” the company said.
Other complexities around the BPaL regimen pertain to effective procurement, since bedaquiline is patented and needs to be sourced from J&J. “So, the program will have to provide bedaquline and linezolid from its own procurement and then procure pretomanid separately from Mylan,” Menghaney added.
Mylan To Evaluate ‘Opportunities’ On Price
Mylan expects to initially make pretomanid available in India via a donation of 400 treatment courses to the NTEP that provides free, anti-TB and care across the country, facilitating access to patients who need it the most. Commercial access to the NTEP is also being provided at the “global access price” of $364 for a six-month treatment course, Mylan said.
The Stop TB Partnership’s Global Drug Facility had in October last year 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 BPaL regimen at $1,040 per treatment course (when bought from the facility at access prices).
On whether Mylan sees scope for paring the global access price as volumes increase, Bamzai said: “We will evaluate opportunities on price according to changes in volume.”
The executive also referred to Mylan’s role, for over a decade, in leading the charge in accelerating access to high-quality and affordable antiretrovirals for people living with HIV across the world.
“Mylan has leveraged partnerships to provide access to innovative antiviral drugs for managing viral hepatitis [hepatitis B and C infection] at a fraction of global cost,” he underscored.
Manufacturing Plans
The US firm also outlined manufacturing plans for pretomanid in India and indicated it is confident of steady supplies despite general industry-wide concerns around supply chain disruptions against the backdrop of COVID-19.
Bamzai said that Mylan will leverage its vast manufacturing platform, capacity and supply chain capabilities to ensure a “sustainable supply” of pretomanid to patients in need.
The drug will be manufactured in one of Mylan’s US Food and Drug Administration-compliant oral solid dosage facilities in India. The company is committed to continue doing its part in support of public health needs and maintaining a "reliable supply" of critical medicines for patients around the world, he stressed.
Steady supplies of TB drugs are critical amid the current pandemic, which has heavily burdened global healthcare systems. In May this year, Survivors Against TB, a community-based network, wrote to India’s Minister of Health and Family Welfare and state government officials flagging news of the deaths of more than 145 TB patients in Agra during the virus-related lock-down.
These deaths, as per some local media reports, occurred in part due to lack of access to TB medication and unavailability of treatment, with healthcare services stretched tackling the surge in COVID-19 cases. India alone accounts for about 25% of the world’s TB burden, with around 2.7 million cases per year; of these, an estimated 130,000 patients have some form of drug-resistant TB.
Global Burden
Earlier this year, a study commissioned by the Stop TB Partnership in collaboration with Imperial College, Avenir Health and Johns Hopkins University, said that with a three-month lock-down and a protracted 10-month restoration of services, global TB incidence and deaths in 2021 would increase to levels last seen between 2013 and 2016, respectively.
This implies a massive setback of at least five to eight years in the fight against the bacterial disease, the study, supported by USAID, added.
It called for supplementary measures and resources to reduce the “accumulated pool” of undetected people with TB, including ramped-up active case-finding alongside intensive community engagement and contact tracing to maintain awareness of the importance of recognizing and responding to symptoms suggestive of TB, using digital technology and other tools.
The study also emphasized that securing access to an uninterrupted supply of quality-assured treatment and care for every single person with TB will be essential.