A public-private partnership yesterday announced plans supporting progression of two investigational tuberculosis (TB) combination treatment regimens into phase 2 clinical development.

The group – Project to Accelerate New Treatments for Tuberculosis (PAN-TB) collaboration – announced the execution of a joint development agreement (JDA) that would evaluate if the novel regimens, which combine registered products and new chemical entities (NCEs), could effectively treat all forms of active pulmonary TB, using substantially shorter treatment durations than existing drug regimens, with the goal of identifying a regimen suitable for phase 3 development.

TB is a major global cause of illness, disability and catastrophic household costs, and is responsible for an estimated 1.5 million deaths yearly worldwide.

A shorter drug regimen that can treat both drug-susceptible and resistant forms in potentially three months or less could provide a significant benefit to both patients and health systems and may overcome the need for accompanying drug-resistance testing.

Recognising that no single organisation produces the full range of drugs to tackle TB, the PAN-TB collaboration brings together philanthropic, non-profit and private sector organisations to accelerate development of novel, shorter drug regimens to treat all forms of the ailment. The five antimicrobial agents, to be evaluated under the new JDA and the organisations contributing them, include: Bedaquiline; registered product for multidrug-resistant TB, Janssen Pharmaceutical NV, part of the Janssen Pharmaceutical Companies of Johnson & Johnson, and NCE for drug-sensitive TB, TB Alliance; Delamanid, registered product, Otsuka Pharmaceutical Co., Ltd; Pretomanid, registered product, TB Alliance; OPC-167832; NCE, Otsuka; and Sutezolid; NCE, TB Alliance, Medicines Patent Pool, Bill & Melinda Gates Medical Research Institute.

The two investigational drug regimen combinations to be evaluated comprise: DBOS – delamanid, bedaquiline, OPC-167832 and sutezolid; and PBOS – pretomanid, bedaquiline, OPC-167832 and sutezolid.

The planned phase 2 trials to be supported by JDA were designed by the PAN-TB collaboration and informed by the World Health Organisation’s (WHO) recently published position statement on the design of clinical trials for novel TB therapies.

New treatment regimens could transform TB care. The most commonly used drug regimen for treatment of drug-sensitive TB requires patients to take multiple drugs for up to six months with routine clinical monitoring. Patients with drug-resistant forms of TB can face longer and more complex treatment journeys, often with significant side effects that require increased monitoring.

Accurate and rapid drug resistance testing is essential for early diagnosis of both drug-sensitive and resistant TB, but access to testing could be limited due to high costs, technical challenges, among other barriers.

The PAN-TB collaboration is a first-of-its-kind effort to accelerate development of a drug regimen capable of treating all forms of TB (a “pan-TB” regimen), focusing on advancing research through phase 2 clinical studies and identifying promising regimens for further work.

The collaboration consists of Evotec, GSK, Janssen Pharmaceutica NV, Otsuka, TB Alliance, Bill & Melinda Gates Medical Research Institute (Gates MRI) and Bill & Melinda Gates Foundation.

The JDA, announced yesterday, of being among the four collaborators contributing drugs, including Janssen Pharmaceutica NV, Otsuka, TB Alliance and Gates MRI that would also conduct the clinical studies.

Global TB Project Leader, Otsuka Pharmaceutical Co. Ltd., Masanori Kawasaki, said: “We are extremely proud to be moving forward within this unique collaboration towards the phase 2 b/c trial of a new universal treatment regimen. We are excited to be working closely with our colleagues in the Bill & Melinda Gates Medical Research Institute, Janssen Pharmaceutica NV and the TB Alliance to do all we can to bring a new treatment to patients whose options are limited. Otsuka is dedicated to research and development to eliminate tuberculosis. We extend our thanks to the Bill & Melinda Gates Foundation for bringing together leaders in the field of TB towards the goal of ending TB for good.”

Global Head of Global Public Health R&D, Janssen Research & Development, LLC, Ruxandra Draghia-Akli, said: “The Janssen Pharmaceutical Companies of Johnson & Johnson remain steadfast in our commitment to advancing research and development to create next-generation TB treatment regimens, as guided by our 10-year initiative to discover and develop new drugs to help end TB. Today, our medicine has become the backbone of WHO-recommended all-oral treatment regimens for nearly all DR-TB patients, and this agreement will allow us to explore further our medicine’s potential to help transform TB treatment for patients in need while maintaining its long-term effectiveness in the face of rising antimicrobial resistance.”

President and CEO, TB Alliance, Mel Spigelman, MD, said: “TB is becoming a greater and greater global health emergency. We are proud to be a member of the PAN-TB consortium to advance novel drug regimens that can much more effectively combat this deadly pandemic and save lives. This initiative is a significant advancement of our pioneering efforts that introduced and validated the concept of regimen development in TB.”