TB Alliance Welcomes New Data on BPaL-Based Regimens Presented at the 2021 Union Conference

New results from operational research in Ukraine and MSF’s TB-PRACTECAL study on drug-resistant forms of tuberculosis to be presented

A team of researchers at an operational research site in Ukraine.

PRETORIA (October 20, 2021)—TB Alliance welcomes new evidence to be presented for the use of short, BPaL-based, six-month regimens for drug-resistant forms of tuberculosis (TB). Médecins Sans Frontières (MSF) and Ukraine’s National Institute of Phthisiology and Pulmonology will each present new data on these regimens at the 52^nd Annual Union World Conference on Lung Health, held virtually from 19-22 October 2021.

BPaL is an all-oral drug regimen consisting of bedaquiline, pretomanid and linezolid. Preliminary results from Ukraine, the first country to conduct operational research on how the treatment performs in clinical practice settings, show that among the first cohort of 55 patients recruited, 46 patients completed their six-month treatment and were sputum negative at the time of the assessment.¹ Of those 46 patients, 93% achieved sputum culture conversion within 1 month and 40% converted within 2 weeks.¹ Reported adverse events included neuropathy, hepatotoxicity and myelosuppression, which were also observed in TB Alliance’s Phase 3 Nix-TB and ZeNix trials of the regimen.^1,2

“Patients suffering from drug-resistant TB face so many obstacles to good health” said Dr. Nataliia Lytvynenko, head of the MDR-TB Research Center at Ukraine’s National Institute of Phthisiology and Pulmonology. “The promise of a more effective treatment, delivered in a shorter period of time has been embraced here in Ukraine. With better treatments we are able to beat back this infectious killer.”

Ukraine has a high burden of TB, particularly drug-resistant forms of the disease. According to the World Health Organization (WHO), the country has the third highest caseload of highly drug-resistant TB after Russia and India and close to 1 in 3 cases of TB in the country are resistant to at least one first-line drug.³ In November 2020, Ukraine became the first country to start operational research (OR), following the WHO’s recommendation of pretomanid as part of the BPaL regimen in TB treatment guidelines for appropriate patients under OR conditions.⁴Responding to these preliminary results, Ukraine’s national program has moved to procure approximately 1,000 treatment courses of the regimen.

“This new evidence shows that shorter and effective treatments for people with highly drug-resistant TB can be delivered within field settings in high-burden countries,” said Dr. Salah Foraida, senior director of Medical Affairs at TB Alliance. “We are excited to see that these results continue to demonstrate the efficacy and tolerability of the BPaL regimen, and also highlight how TB Alliance products can have a real impact on the lives of patients around the world.”

TB Alliance also welcomes the announcement of new data from the TB-PRACTECAL clinical trial, sponsored by MSF. TB Alliance is a proud partner of the trial, which is evaluating three BPaL-based regimens for the treatment of drug-resistant TB compared to a standard of care arm. Top-line results from two of the arms demonstrated a significant improvement in outcomes between the regimen containing BPaL and moxifloxacin compared to regimens considered the local standard of care in the three countries where the trial was run (Belarus, South Africa and Uzbekistan).⁵ These results were announced today by MSF and will be presented during a Union Conference symposium on Friday, October 22.

Top-line results from TB Alliance’s ZeNix trial will also be discussed at the conference during a symposium co-hosted by KNCV Tuberculosis Foundation. ZeNix is a four-arm, randomized, double-blinded study as to dosage and duration of linezolid that enrolled 181 patients with highly drug-resistant forms of TB in South Africa, Russia, Georgia and Moldova. Patients were treated for six months with bedaquiline (developed by Janssen), pretomanid (developed by TB Alliance as part of BPaL) and varying doses and durations of linezolid, with follow up reported thus far to the primary endpoint for all patients six months after completion of treatment. Primary endpoint results for ZeNix were included in an oral abstract presentation earlier this year at the IAS Conference on HIV Science, showing the primary efficacy analysis for participants in all four arms of the study ranging from 84% to 93%, with reduced side effects associated with lower exposure to linezolid.⁶

“The evidence we’ve seen from these studies—from Nix-TB to ZeNix, operational research, and now in TB-PRACTECAL—underscores the potential of short, all-oral BPaL-based regimens for patients,” said Mel Spigelman, president and CEO of TB Alliance. “We look forward to advancing our work to find better cures for all forms of TB and exploring new pathways and therapeutic approaches to treat this deadly infectious disease.”

About Operational Research in Ukraine
This operational research study is entitled “Pilot study to assess the effectiveness and safety of antimycobacterial therapy with BPaL in Ukraine.” The study is being conducted by Ukraine’s National Institute of Phthisiology and Pulmonology within the project "Development of evidence base for the introduction of the latest short-term treatment regimens for drug-resistant tuberculosis in Ukraine,” implemented by local NGO OATH with technical support from KNCV Tuberculosis Foundation and sponsored by the Stop TB Partnership’s TB REACH program. Preliminary results will be presented on Thursday, October 21 at a symposium during the Union World Conference on Lung Health.

About TB Alliance
TB Alliance is a not-for-profit organization dedicated to finding faster-acting and affordable drug regimens to fight TB. Through innovative science and with partners around the globe, we aim to ensure equitable access to faster, better TB cures that will advance global health and prosperity. TB Alliance operates with support from Australia’s Department of Foreign Affairs and Trade, Bill & Melinda Gates Foundation, Foreign, Commonwealth and Development Office (United Kingdom), Cystic Fibrosis Foundation, Germany’s Federal Ministry of Education and Research through KfW, Global Disease Eradication Fund (Korea), Global Health Innovative Technology Fund, Indonesia Health Fund, Irish Aid, Korea International Cooperation Agency, Medical Research Council (United Kingdom), National Institute of Allergy and Infectious Diseases, Netherlands Ministry of Foreign Affairs, Republic of Korea’s Ministry of Foreign Affairs, and the United States Agency for International Development. For more information, visit www.tballiance.org.

References

1. Lytvynenko N. (2021) October 21. BPaL regimen for treatment of highly drug-resistant tuberculosis under operational research conditions: Ukraine experience, safety, and end of treatment outcomes [Conference presentation]. Union Conference 2021.

2. Conradie F. (2021) July 21. High rate of successful outcomes treating highly resistant TB in the ZeNix study of pretomanid, bedaquiline and alternative doses and durations of linezolid [Conference presentation]. IAS 2021, Berlin, Germany.

3. World Health Organization (2021). Global Tuberculosis Programme. Available at: who.int/teams/global-tuberculosis-programme/data.

4. KNCV, (2020) November 23. Available at: kncvtbc.org/en/2020/11/23/ukraine-tb-patients-first-to-receive-groundbreaking-new-drug-regimen/

5. Nyang'wa BT. (2021) October 22. TB-PRACTECAL: trial results and next steps [Conference presentation]. Union Conference 2021.

6. Conradie F. (2021) July 21. High rate of successful outcomes treating highly resistant TB in the ZeNix study of pretomanid, bedaquiline and alternative doses and durations of linezolid [Conference presentation]. IAS 2021, Berlin, Germany.