endTB Partnership Launches Clinical Trial to Target Toughest Strains of TB

Médecins Sans Frontières (MSF), Partners In Health (PIH) and other leading medical organizations have launched a major clinical trial which seeks to revolutionize treatment for the toughest strains of tuberculosis (TB). The first patient started treatment in Georgia earlier this month.

This phase III clinical trial is part of a UNITAID-funded transformative project called endTB, which aims to speed up and expand access to better and shorter treatments for drug-resistant forms of TB. The four-year, US$60 million project, being implemented by PIH, MSF and Interactive Research and Development (IRD), targets 15 countries across three continents. The trial uses bedaquiline and delamanid to find radically shorter (9 months), injection-free, more tolerable treatments for MDR-TB. These new drugs will be combined into experimental new treatments with other oral TB drugs such as clofazimine, linezolid, fluoroquinolones and pyrazinamide.

The endTB project is expected to enroll an estimated 2,600 MDR-TB patients on treatment with the new TB drugs, and 750 patients will take part in a clinical trial across six countries: Georgia, Kazakhstan, Kyrgyzstan, Lesotho, Peru and South Africa.

As stated by Dr. Carole Mitnick, co-principal investigator of the endTB clinical trial from PIH and Harvard Medical School, “Together, PIH and MSF have expanded structures, resources, treatment, evidence, and ambitions for this and other complex diseases affecting poor people. The endTB clinical trial is a natural extension of this decades-long collaboration between two organizations that place priority on expanding access to proven, high-quality interventions among patients who need them, regardless of economic or socio-political situations in which they live.”

Read the full press statement here.

Advocates call on Sequella to provide open access to sutezolid data

In an open letter sent to Sequella on 21 February 2017, TB advocates called attention to the recent agreement between Johns Hopkins University and the Medicines Patent Pool regarding the rights to develop sutezolid in combination for TB, and urged Sequella to provide open access to all existing clinical data for sutezolid to facilitate and accelerate its further clinical development.

“We now appeal to Sequella to act in the interest of public health and provide open access to all existing sutezolid data. In the absence of this data, researchers will have to redo studies, wasting precious resources and time, and delaying both sutezolid’s advancement and urgently needed, better treatment options for TB patients.”

Read the full letter here.

TB community demands WHO include TB on “Priority Pathogens” list

On February 27, the WHO released its first Global priority list of antibiotic-resistant bacteria to guide research, discovery and development of new antibiotics, which includes 12 families of bacteria that “pose the greatest threat to human health”. The WHO excludes M. tuberculosis from this “Priority Pathogens” list, and has subsequently sparked fierce controversy within the infectious disease and public health communities. A number of organizations have submitted letters of protest to the WHO demanding that M. tuberculosis be included on the list, including the International Union Against Tuberculosis and Lung Disease, the TB Alliance, and the Stop TB Partnership.

Learn more about the TB community’s response through the links below:

The World Health Organization made a big mistake on TB. It must fix it.

Global TB Community Reaction to Exclusion of TB from WHO List of Bacteria in Need of New Antibiotics

 

India plans to expand access to new TB drug

The Delhi High Court’s ruling in the recent landmark lawsuit that granted an 18-year old Indian girl with XDR-TB access to bedaquiline has led health advocates to seek inclusion of delamanid in the Indian government’s Revised National Tuberculosis Control Program. “It is time the government enforces public health safeguards in the patent law and licenses the drug to generic firms so that they can manufacture it for government supplies,” said Paul Lhungdim from the Delhi Network of Positive People.

Read more about the results of the lawsuit and how patient advocacy groups are moving forward here.

Two new drug therapies might cure every form of tuberculosis

Two new drug therapies may have be able to cure all forms of tuberculosis, including the forms that are most difficult to treat.  The treatments, called BPaMZ and BPaL, have the potential to make TB treatment simpler and more effective.  BPaMZ involves taking four drugs once a day, and initial trial results suggest that it cures nearly all cases of ordinary TB in four months, and most people with DR-TB in approximately six months.  BPaL involves taking three drugs once a day, and has so far cured 40 of 69 patients with XDR-TB within six months.  “We will have something to offer every single patient,” stated Mel Spigelman, president of the TB Alliance. “We are on the brink of turning TB around.”

Read the full article here and find out more about the two new regimens.

Shorter regimen for MDR-TB in sight

The TB Alliance conducted a phase two clinical trial aimed at developing and testing a new drug regimen for MDR-TB patients called BPaMZ, which consists of four oral drugs: bedquiline, pretomanid, moxifloxican and pyrazinamide. Over an eight-week period, patients treated with the new BPaMZ regimen cleared M. tuberculosis bacteria from their sputum up to 3.5 times faster than patients who received standard treatments. “The next step is to do a phase three trial, on about 1,200 patients – if we have positive results from that we can apply for regulatory approval from authorities,” stated the TB Alliance’s Dr. Christo van Niekerk.

The TB Alliance presented its findings from the BPaMZ trial at the Conference on Retroviruses and Opportunistic Infections that took place in Seattle in February.

Read more about the trial and next steps here.

WHO Interim Policy Guidance on the Use of Delamanid in the Treatment of MDR-TB in Children and Adolescents

The use of delamanid in the treatment of MDR-TB was recommended by the World Health Organization in 2014. However, these interim policy recommendations were limited to adult MDR-TB patients under very strict conditions. In view of recent data on the use of delamanid in children diagnosed with MDR-TB, the WHO convened an independent, multidisciplinary, international expert panel to assess new data and develop an addendum to the 2014 interim guidance on delamanid, with specific recommendations to paediatric MDR-TB patients.  Based on the assessment of this evidence and recommendations from the expert panel, the WHO now recommends that delamanid may be added to the WHO-recommended longer regimen in children and adolescents (6 – 17 years).

Read the full report here.

 

TB-PRACTECAL Recruits First Patient

The Médecins Sans Frontières (MSF) sponsored clinical trial, TB-PRACTECAL, has begun. The trial’s first patient was randomized and started treatment on January 17, 2017 at the trial site in Nukus, Uzbekistan. In parallel to enrollment at the Nukus study site, additional sites are being upgraded and readied for recruitment in the KwaZulu-Natal province in South Africa by THINK (TB & HIV Investigative Network), in Minsk, Belarus, and in Tashkent, Uzbekistan. TB-PRACTECAL is a multi-centre, open label, multi-arm, randomized controlled phase II-III trial that aims to evaluate short treatment regimens containing bedaquiline and pretomanid in combination with existing anti-TB drugs for the treatment of MDR and XDR-TB.

More information about the trial can be found at:
https://clinicaltrials.gov/ct2/show/NCT02589782?term=TB-PRACTECAL&rank=1
https://www.msf.org.uk/content/tb-practecal

WHO Welcomes New Agreement Between Medicines Patent Pool and Johns Hopkins University on the Development of Sutezolid for TB Treatment

The World Health Organization welcomes a new licensing agreement between the Medicines Patent Pool (MPP) and Johns Hopkins University to facilitate the clinical development of the TB drug candidate sutezolid. Phase I trials indicated that sutezolid has action mechanisms similar to those of linezolid, the commercially-available oxazolidinone antibiotic in the same class, but that sutezolid is more potent and less toxic than linezolid. Although sutezolid reached Phase IIa clinical development, there have been no advances since 2013.

“The MPP-John Hopkins University agreement is an extraordinary step as it seeks to jump-start currently stalled development on a compound that showed promise in early stage trials,” said Mario Raviglione, Director of the Global TB Programme at the World Health Organization (WHO). “The current scarcity of treatment options is threatening to derail the WHO’s global targets to slash TB deaths by 90% by 2030. We are in urgent need of new and better combination regimens, especially for patients with MDR-TB, and the inclusion of sutezolid might bring great benefit.

“Sutezolid has been considered a promising investigational treatment that, if further developed in combination with other drugs, could be used to more effectively treat both drug-sensitive and drug-resistant TB in patients,” added Dr Christian Lienhardt, Team Leader, Research for TB Elimination, WHO Global TB Programme. “We commend the Medicines Patent Pool for its new commitment to facilitate treatment options for TB patients.”

Indian Girl with XDR-TB Wins Access to Bedaquiline

India’s Ministry of Health agreed to grant access to bedaquiline to an 18-year old girl suffering from extremely drug-resistant tuberculosis (XDR-TB). The girl, who was diagnosed with XDR-TB in 2013, was previously unable to receive treatment with bedaquiline due to stringent restrictions on the new drug’s use in India.  The girl’s father brought her predicament to court, asking that the Delhi High Court direct the government to administer the drug immediately to his daughter.  On January 18th, 2017, following a month-long deliberation process that has been closely followed by public health experts across the globe, the High Court decided to grant the girl access to bedaquiline.

Read more about the lawsuit and hearing here.