Paris / Boston / Dubai – International organizations Partners In Health (PIH), Médecins Sans Frontières (MSF), Interactive Research and Development (IRD) and their financial partner UNITAID will start in April the endTB project, a partnership aimed at radically changing the management of multidrug-resistant tuberculosis (MDR-TB).
By 2019, endTB will provide access to two new anti-TB drugs (bedaquiline and delamanid), for 2,600 MDR-TB patients in 16 countries. These are the first new anti-TB drugs developed in over 50 years and these drugs offer new hope to patients suffering from MDR-TB. endTB will use the new anti-TB drugs according to World Health Organization (WHO) recommendations in a closely monitored group of patients. And, an innovative endTB clinical trial will test completely novel MDR-TB treatment regimens in 600 more MDR-TB patients. The shorter, more user-friendly regimens being tested will be nothing short of revolutionary if they are found to be safe and effective.
Although approved for treatment of MDR-TB for more than a year, the two drugs have scarcely been used. Access to the new drugs in countries with high burdens of MDR-TB has been almost exclusively through compassionate use programs, requiring a case-by-case authorization from the manufacturer for patients with no other treatment options.
As of today, it is estimated that fewer than 1,000 patients have received bedaquiline. Although delamanid is provided through compassionate use, it has yet to reach more than handful of patients. endTB, however, will lay the ground work for appropriate delivery of these drugs to hundreds of thousands of patients suffering from MDR-TB.
“The main obstacle today is that there is limited knowledge about these drugs. Many of the countries where the patients in need live are not in the position to provide the enhanced safety monitoring that is still needed for their use,” said Dr. Aamir Khan, end TB project leader at IRD. “Also, in most of countries bedaquiline and delamanid are not licensed. And even in countries where they are registered, drug procurement mechanisms are today extremely long and complicated.”
Current treatment for tuberculosis (TB) consists of six months on a cocktail of various antibiotics. MDR-TB is defined as the resistance of the TB bacterium to at least the two most powerful first-line antibiotics, rifampicin and isoniazid. The extreme form of MDR-TB, known as extensively drug resistant TB (XDR-TB), occurs when resistance appears to second-line drugs too.
Out of the estimated 500,000 people that develop MDR-TB every year, about 10% are XDR-TB. Currently, there are very few drugs with good efficacy for these patients; the drugs have to be combined in treatments that last up to two years, with severe side effects and only 50% success rate for MDR-TB overall – less than 20% for XDR-TB.
“We see every day how long, painful, and ineffective the current treatments for DR-TB patients are,” said Dr. Michael Rich, end TBproject leader in PIH. “For decades, we have been running after the disease, waiting for new tools to fight it. Today we have a chance to get the upper hand on TB. But in order to do so, we have to act quickly and set the framework for the optimal and effective use of these new drugs.”
In countries where bedaquiline has been provided to XDR-TB patients through compassionate use, outcomes are extremely encouraging. In Armenia, for instance, after 6 months of treatment in an MSF-supported program, the TB bacillus was eliminated from the sputum of 85% of patients.
“These drugs bring a renewed hope for patients, and for caregivers. But drugs alone are a half-victory,” said Dr. Francis Varaine,end TB project leader in MSF. “We need to gather more evidence on the safety, the efficacy and the effectiveness of those drugs when they are combined with other drugs, as well as the ideal length of the treatment and the associated side effects, amongst others parameters. Only then we will really be able to change the game in the fight against MDR-TB.”
“This project will help make MDR-TB treatment more effective and easier-to-bear, thereby helping to halt the disease’s spread,” said Lelio Marmora, Executive Director of UNITAID. “This new investment is part of our broader portfolio that introduces innovations for a more effective global TB response. These new medicines to treat drug resistant TB are so urgently needed, in part due to the success in recent years in detecting cases, with a three-fold increase since 2009.”
About the end TB partnership
The 4-year project will officially start on April 1st. It is funded by a UNITAID grant of up to 60,4 million US$. Enrollment of a minimum of 2 600 MDR-TB patients who will receive new TB drugs (bedaquiline or delamanid) will take place in 16 countries: Armenia, Bangladesh, Belarus, Democratic People's Republic of Korea, Ethiopia, Georgia, Kazakhstan, Kenya, Kyrgyzstan, India, Indonesia, Lesotho, Myanmar, Nepal, Pakistan and Peru.
Each patient will be monitored closely for response to treatment and for potential adverse events.
Clinical trials will take place in five sites (currently under selection), and will study the safety and efficacy of several 'user-friendly' MDR-TB treatment regimens, each containing one new drug. The enrollment of patients will start in late 2015. Treatments combining both bedaquiline and delamanid might be explored in a following phase of the trials, if other studies support their combination.
The project will also reduce existing country-level barriers to the uptake of new TB drugs. It will provide evidence to facilitate their registration in countries, advocate for simple and swift procurement mechanisms. Moreover, the project will build a broader evidence-base for WHO recommendations for the use of new TB drugs.
About bedaquiline and delamanid
Bedaquiline (Sirturo™) and delamanid (Deltyba™) are the first two new drugs developed in nearly 50 years. They are manufactured by Janssen Pharmaceuticals and Otsuka Pharmaceutical, respectively. Bedaquiline was conditionally approved by the Food and Drug Administration (FDA) at the end of 2012, for the treatment of adults with MDR-TB. Delamanid was recommended conditional marketing authorization by the European Medicines Agency (EMA) in November 2013. Both have shown efficacy against TB in phase II trials. Phase III trials are currently ongoing for delamanid.
UNITAID is a global health organization that invests to bring innovation to the global responses for HIV/AIDS, tuberculosis and malaria, enabling more efficient and effective efforts for the three diseases. Since its creation in 2006, it has invested over $260 million in drug resistant tuberculosis. Its current TB investments are focused on expanding access to new MDR-TB medicines via the endTB project while maintaining access to existing medicines through the Strategic Rotating Stockpile, scaling up detection of TB including drug resistant strains through its EXPAND-TB and TBXpert projects, and introducing child-adapted medicines for the over half a million annual paediatric cases.
Médecins Sans Frontières / Doctors Without Borders (MSF) is an international, independent, medical humanitarian organization that delivers emergency aid to people affected by armed conflict, epidemics, natural disasters and exclusion from healthcare. Today, MSF has operations in nearly 70 countries.
MSF has been involved in Tuberculosis care for 30 years, and opened its first programmes to treat multi-drug resistant tuberculosis in 1999. MSF is one of the largest NGO treatment providers of drug-resistant tuberculosis. In 2013, the organization treated 29,900 patients with tuberculosis worldwide, including 1,950 patients with drug-resistant tuberculosis.
Currently MSF provides access to bedaquiline and delamanid to 75 patients in Armenia, Georgia and Kenya.
Partners In Health is a global health organization relentlessly committed to improving the health of the poor and marginalized. PIH builds local capacity and work closely with impoverished communities to deliver high-quality health care, address the root causes of illness, train providers, advance research, and advocate for global policy change. PIH began treating MDR-TB in 1995, and has since implemented community-based treatment programs for MDR-TB in multiple countries, including Peru, Russia, Haiti, Lesotho and Kazakhstan.
IRD is a global health delivery and research organization based in Dubai that works in 15 countries, including high-burden MDR-TB countries such as Pakistan, Indonesia, and Bangladesh. The IRD team leverages process and technology innovations to address global health delivery gaps, including the use of health market innovations such as social business models to engage private providers in lung health and diabetes care, as well as the use of performance-based incentives for community screeners and treatment supporters, patient incentives to enable treatment compliance, and the use of open source information technology platforms to allow close monitoring of patient care and program quality.