New patient-friendly TB preventive therapy to be rolled out in five high-burden TB countries at affordable price

Johannesburg (3 February 2021) — A new fixed-dose combination (FDC) of “3HP”, a short-course tuberculosis (TB) preventive treatment (TPT) combining two drugs, rifapentine and isoniazid, is starting to be rolled out in five TB high burden countries in Africa. This will reduce the number of pills that people who need the treatment have to take every week from nine to three. Enough treatments for up to 3 million patients are expected to be made available for eligible countries this year.

As the result of an agreement concluded by Unitaid, the Clinton Health Access Initiative (CHAI) and the manufacturer of the FDC, Macleods, the latter has agreed to offer a ceiling price of US$15 (ex-works) for a three-month patient course of weekly rifapentine and isoniazid. Thanks to the IMPAACT4TB project funded by Unitaid and led by the Aurum Institute, five initial countries from a total of 12 targeted by the end of the year, will start providing the FDCs in February and March 2021: Ethiopia, Ghana, Kenya, Mozambique, and Zimbabwe. Other countries are expected to receive supplies with the support of PEPFAR and the Global Fund to Fight HIV, Tuberculosis and Malaria.

The partnership with Macleods will bolster efforts to treat TB infection also known as “latent TB” – currently estimated to affect one-quarter of the world population – by broadening access to shorter and easier to use preventive therapies. As part of a wider access strategy to facilitate the introduction of generic rifapentine-based formulations in low- and middle-income countries (LMICs), it will contribute to move towards the United Nations High-level Meeting (HLM) target to provide TPT to at least 30 million people by 2022.

“WHO welcomes the new fixed-dose combination TB preventive treatment that will result in reducing the pill burden for people with TB infection, enabling better adherence and outcomes,” said Dr Tereza Kasaeva, Director of World Health Organization’s (WHO) Global TB Programme. “This collaboration between Unitaid, the Clinton Health Access Initiative and manufacturers has been vital to support the uptake of TB preventive treatment as recommended in WHO guidelines. We now look forward to a surge in action from national programmes supported by donors and partners to scale-up access to TB preventive treatment and reach the UN High-Level Meeting targets.”

People with TB infection, often dubbed latent, have no symptoms, are not contagious and most do not know they are infected. Without treatment, 5% to 10% of these people will develop active TB, the form which makes people sick and can be transmitted from person to person.

The agreement establishing the US$15 price and other access conditions was concluded by Unitaid, the Clinton Health Access Initiative (CHAI) and Macleods. The price will be available to government institutions in 138 LMICs, as well as for the international organizations in charge of the procurement.

“The ceiling price agreement negotiated with Macleods is another example of our commitment to ensure that effective, quality-assured and affordable TB preventive therapies are made available in low- and middle-income countries,” said Robert Matiru, Director of the Programme Division at Unitaid. “Beyond this deal, we will continue working hard to ensure a healthy market for all manufacturers that wish to develop and commercialize rifapentine-based products.”

The first phase of the access strategy resulted in a price discount offer by Sanofi for rifapentine 150 milligram tablets (Priftin®), announced in 2019, lowering a patient treatment course of Priftin® from US$45 to US$15.

“The availability of a shorter, more easily tolerated, and safer regimen for TB prevention that is also affordable is critical for accelerating the fight against TB,” said Dr. Angeli Achrekar, Acting U.S. Global AIDS Coordinator. “This also has important implications for the HIV response, as TB remains the leading cause of death for people with HIV around the world.”

With both Sanofi and Macleods expected to ramp up their production in 2021, Unitaid expects that there will be global availability of enough 3H to reach more than 3 million patients in eligible countries this year, across both manufacturers.

“2020 was a hard year for TB prevention and treatment, as many services were disrupted by lockdowns,” said Prof. Gavin Churchyard, founder and CEO of the Aurum Institute. “But with the roll-out of this new FDC, alongside the existing formulation provided by Sanofi, I’m feeling a renewed sense of optimism that we can get back on track to meet our ambitious global TB prevention goals. Saving lives is the priority. We lose in the end if COVID-19 mortality goes down, but TB rates go up.”

With the FDC, a complete course of treatment for eligible adults is included in one box, addressing many concerns about the pill burden of 3HP and ensuring that TPT can be provided conveniently for individuals at risk for TB.

With this more convenient product in hand that is easier to dispense, take and adhere to, the IMPAACT4TB consortium members are now working to accelerate the delivery of 3HP in 12 high TB burden countries in Africa, Asia, and South America.

For its part, USAID, the largest bilateral funder of TB efforts globally, has been a leader in partnering with high burden TB countries in the successful implementation of their national TB strategies for over 20 years. Preventive TB treatment is a cornerstone of USAID’s Global Accelerator to End TB, which builds countries’ commitment and capacity to reach the United Nations HLM TB targets by 2022. Having a shorter FDC TPT regimen available at a relatively low price will enable USAID to work with partners and stakeholders to rapidly scale up TPT for all who would benefit from it in high burden countries.

Additional quotes

“The availability of this new fixed-dose combination is good news for everyone, especially patients and their families,” said Ahmed Bedru, KNCV Tuberculosis Foundation country representative, leading 3HP implementation for Ethiopia. “Getting people to adhere to a treatment when they are not sick has always been a challenge. The lower number of pills — three pills versus nine pills for an adult — means the treatment is now easier to take, stick to and complete.”

“I’ve started to notice patients taking their medication without difficulties or complaints,” said Dr. Tafadzwa Priscilla Sibanda, Medical Director of the Mpilo Centre and a public health specialist working with the AIDS Healthcare Foundation in Zimbabwe. “It really helps that the 3HP regimen is short. When we explain the doses to patients, they can see the light at the end of the tunnel, and they are encouraged knowing that they will complete the course within 12 weeks.”

“Adherence is always a challenge, especially when people have to take many pills for long periods. But 3HP is changing that. The FDC allows patients to take just three pills once a week for 12 weeks. This will be so much better,” said Dr Pereira Zindoga, a clinician with the Mozambique Ministry of Health’s National TB Program.

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About TB infection

In 2019 alone, 10 million people fell ill from TB, which killed close to 1.5 million people, over 95% of whom were living in low- and middle-income countries. About one-quarter of the world’s population is infected with TB bacilli and most of them do not have the disease and are not contagious. If left untreated, TB infection may progress to TB disease, the form of TB that makes people sick and is capable of being transmitted from one person to another. TPT regimens like 3HP lower the risk of progression in people at risk.

About 3HP: Using the FDC, the once-weekly dose over 12 weeks — a complete course of treatment for eligible adults — is contained in one box. This formulation addresses many concerns about the pill burden of 3HP and will ensure that TPT can be provided conveniently for programmes, providers and individuals at risk for TB. 3HP offers many benefits for infected individuals, clinicians and programs compared to the previous standard of care, when patients were required to take a pill daily for six months or more.

About IMPAACT4TB: Unitaid is investing US$59 million in the Aurum Institute’s IMPAACT4TB project, to protect people most vulnerable to developing active TB. IMPAACT4TB is led by the Aurum Institute in consortium with the Clinton Health Access Initiative, KNCV Tuberculosis Foundation and John Hopkins University, in collaboration with the World Health Organization (WHO) and the Global Drug Facility (GDF). The four-year grant will prioritize short-course TB preventive treatment for people living with HIV and children under five, and subsequently all those in close contact with TB patients in 12 high-burden countries. The target groups will receive a quality-assured, affordable, short-course TB preventive treatment known as 3HP, consisting of high-doses of two antibiotics that treat TB (isoniazid and rifapentine given weekly for three months). www.unitaid.org and www.impaact4tb.org

South Africa’s Aurum Institute is spearheading the TB prevention project and is working with the Clinton Health Access Initiative, KNCV Tuberculosis Foundation, and John Hopkins University, in collaboration with the World Health Organization and the Global Drug Facility.

About Aurum: Established in 1998, the Aurum Institute is an African Public Benefit Organization whose mission is to improve the health of people and communities living in poverty through innovation in global health research, systems and delivery. It is rooted in Africa and is dedicated to researching, supporting and implementing innovative, integrated approaches to global health with their headquarters in South Africa with offices in the U.S.A, Ghana and Mozambique. The Aurum Institute has developed itself into a leading player, bridging the worlds of research, policy and implementation for impact. www.auruminstitute.org

About Unitaid: Unitaid is a global health agency engaged in finding innovative solutions to prevent, diagnose and treat diseases more quickly, cheaply and effectively, in low- and middle-income countries. Its work includes funding initiatives to address major diseases such as HIV/AIDS, malaria and tuberculosis, as well as HIV co-infections and co-morbidities such as cervical cancer and hepatitis C, and cross-cutting areas, such as fever management. Unitaid is now applying its expertise to address challenges in advancing new therapies and diagnostics for the COVID-19 pandemic, serving as a key member of the Access to COVID Tools Accelerator. Unitaid is hosted by the World Health Organization. www.unitaid.org

About WHO: The Global Tuberculosis Programme of WHO works towards the goal of a world free of TB, with zero deaths, disease and suffering due to the disease. The team’s mission is to lead and guide the global effort to end the TB epidemic through universal access to people-centred prevention and care, multisectoral action and innovation. As part of its core functions, the Global Tuberculosis Programme develops policy options, norms and standards for TB prevention and care and facilitates their implementation.

About PEPFAR: Through the U.S. President’s Emergency Plan for AIDS Relief (PEPFAR), the U.S. government has invested over $85 billion in the global HIV/AIDS response, the largest commitment by any nation to address a single disease in history, saving over 20 million lives, preventing millions of HIV infections, and accelerating progress toward controlling the global HIV/AIDS epidemic in more than 50 countries.

About the Johns Hopkins Center for Tuberculosis Research: The Johns Hopkins Center for TB Research was founded in 1998 to contribute to global tuberculosis control through innovative research and training. Its research efforts span the fields of epidemiology, clinical trials, diagnostics and basic science, with faculty from six departments in the Johns Hopkins University Schools of Medicine, Public Health and Nursing. Clinical research sites are located in Baltimore City, Maryland, as well as sites in Brazil, South Africa, India, and other TB high burden countries. http://tbcenter.jhu.edu/

About KNCV Tuberculosis Foundation: KNCV Tuberculosis Foundation has been fighting TB since its establishment in 1903. Over these 117 years, the organization has acquired indispensable knowledge and experience in the field of effective TB control, resulting in significant contributions to global evidence generation, policy development and TB program implementation worldwide. KNCV has extensive international technical experience in supporting those countries preparing to introduce new drugs and regimens. www.kncvtbc.org

About the Clinton Health Access Initiative, Inc. (CHAI): CHAI is a global health organization committed to saving lives and reducing the burden of disease in low-and middle-income countries. We work with our partners to strengthen the capabilities of governments and the private sector to create and sustain high-quality health systems that can succeed without our assistance. For more information please visit www.clintonhealthaccess.org

About Treatment Action Group (TAG): TAG is an independent, U.S based activist and community-based research and policy think tank fighting for better treatment, prevention, a vaccine, and a cure for HIV, tuberculosis, and hepatitis C virus. TAG is the community engagement lead under the IMPAACT4TB project. www.treatmentactiongroup.org

About the Global Drug Facility (GDF): GDF is the world’s largest procurer of TB medicines and diagnostics. Since its creation in 2001, GDF has facilitated access to TB medicines and diagnostics in more than 145 countries, making quality-assured treatments available to over 36 million people with TB. In 2020 alone, GDF delivered more than USD300 million worth of TB medicines and diagnostics to 123 countries. GDF has led the introduction of all-oral regimens for drug-resistant-TB, child-friendly medicines for drug-sensitive and drug-resistant TB, and advanced diagnostics Since 2012, GDF has secured price reductions of over 50% for most second-line TB medicines, primarily by reducing risk to suppliers and minimizing their transaction costs. http://www.stoptb.org/gdf/

Source: IMPAACT4TB