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Innovation challenge: You can't do it alone

On 14 August, the TB Alliance, a “not-for-profit organization dedicated to the discovery, development and delivery of better, faster-acting and affordable tuberculosis drugs that are available to those who need them”, announced that the FDA approved Pretomanid, a new treatment for highly drug-resistant forms of tuberculosis [1]. Pretomanid was approved as part of a three-drug, six-month, all-oral regimen for the treatment of people with extensively drug-resistant TB (XDR-TB) or multidrug-resistant TB (MDR-TB) who are treatment-intolerant or non-responsive (collectively “highly drug-resistant TB”). The combination, referred to as BPaL regimen, consists of bedaquiline, pretomanid and linezolid.

This was big news! Primarily because a new molecule in combination with existing treatments will save lives. But also because the product was developed (mainly) by a not-for-profit organization and not (only) by the private pharmaceutical industry.

There has been much talk in town that public, not for profit organizations should develop medicines moving forward, rather than the pharmaceutical industry. So why wasn’t there more noise about Pretomanid over the news-dire summertime? It might be because in Europe, the registration procedure is still ongoing. A marketing authorization application was submitted to the EMA in May 2019, after the FDA application.

But let’s look at how Pretomanid came to be. As with any medicine development, it is a long story that involves many actors, in both the public and private sector:
  • 1970s: A new class of molecules, nitroimidazole derivatives, were synthesized. Amongst several nitroimidazoles, some were found to have good anti mycobacterial properties. Ciba Geigy developed CGI017341 as the lead compound. But later it was found to be mutagenic (i.e. likely to change the patients’ DNA) and research stopped.
  • 1995: One failure on a compound doesn’t mean failure in the entire field and research on nitroimidazole derivatives continued. In 1995 the PathoGenesis Corporation identified a promising series of nitroimidazopyrans for the treatment of TB and related mycobacterial diseases. PA-824 was discovered during a screening of substituted nitroimidazopyrans as potential anti-tubercular agents [2]. PathoGenesis started preclinical development of PA-824.
  • In 2000, Chiron acquired PathoGenesis, including PA-824 and all research results into this agent.
  • In 2002, Chiron licensed the development of PA-824 (and its analogs) to the Global Alliance for TB Drug Development, with a commitment to make the TB technology available royalty-free in endemic countries.
  • 2019: The TB Alliance carried forward the development of PA-824, leading to the announcement of the approval of Pretomanid on 14 August 2019 as part of the BPal regimen [3]. Research on analogs of PA-824 continues.
Is it not fascinating to see the collaborative activity in pre-clinical research and the number of entities (whether companies or other research organisations) involved? And it does not stop there.
Pretomanid is approved in combination with two additional products:
  • bedaquiline from Janssen and
  • linezolid, available from multiple manufacturers, including Mylan.
When it comes to commercialization of Pretomanid, the TB Alliance announced they entered into a licensing deal with Mylan.

So what is our take from this long story? Maybe I am being over-simplistic, but I feel there is no such black and white thing as private sector development versus public sector development…
All actors are inextricably intertwined and have their role to play…
in-house research becomes public and can be shared thanks to intellectual property rights and can be licensed out…
the private industry licenses in and out and acquires companies, as do not-for-profit institutions, allowing competitors to work together…
failures are common but allow to move forward in research…
multiple projects are ongoing in parallel leading to different treatment options for those in need…
Is Pretomanid actually an example of how successful model of collaborative pharmaceutical development is?



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[1] https://www.tballiance.org/news/fda-approves-new-treatment-highly-drug-resistant-forms-tuberculosis
[2] Another promising compound was OPC-67683, which in the meantime was developed by Otsuka into Delamanid, approved by the EMA in 2014.
[3] https://www.tballiance.org/pathway-potential-new-tb-treatments

Edith Frénoy

Edith Frénoy is EFPIA Director Market Access and HTA Policy lead
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