WHO issues a position statement on the use of delamanid for MDR-TB following an expedited review of phase III clinical trial results

This Position Statement by the World Health Organization (WHO) on the use of delamanid in the treatment of multidrug-resistant tuberculosis (MDR-TB) has been developed in response to the final data from the phase III, multicentre, randomized, double-blind, placebo-controlled clinical trial to evaluate the safety and efficacy of delamanid (Trial #242-09-213, hereafter referred to as ‘Trial 213’). The final Trial 213 data were released in late November by the manufacturer (Otsuka Pharmaceutical, Japan) to WHO and to the European Medicines Authority (EMA) in compliance with EMA regulatory requirements. The original trial protocol and subsequent amendments are registered (#NCT0142670) in the US/NIH clinical trials register (https://clinicaltrials.gov/ct2/show/NCT01424670).

WHO conducted an expedited external expert review of the data on Trial 213 data in early December 2017 in order to assess the implications of the results on the 2014 and 2016 interim policy guidance. As data from ongoing observational studies using delamanid are not yet available for review, this document is focused on the results of Trial 213 and its immediate policy implications.

To download and read the position statement, click here.

Webinar Series: New XDR-TB Regimens containing Pretomanid, January 11th

On Thursday, January 11, 2018 by Dr. Dan Everitt, Vice President and Senior Medical Officer at TB Alliance, presented on New XDR-TB Regimens containing Pretomanid.

Dr. Dan Everitt, MD, of the Global Alliance presented the results of an important study of a six-month treatment regimen for XDR-TB using bedaquiline, pretomanid and linezolid, the NiX-TB trial. In addition, the Alliance expects to launch the ZeNix trial in late 2017. This clinical trial, to optimize the use of linezolid with bedaquiline and pretomanid, is expected to be conducted across 10 trial sites in South Africa, Georgia, Belarus, and Russia. Study design and current status was presented on the Webinar.

A copy of the presentation slides will be made available shortly.

Health ministry approves new tuberculosis drug

“New Delhi: Perturbed by the increasing number of multi-drug resistant (MDR) and extensive drug resistant (XDR) tuberculosis cases in India, the health ministry has approved the use of a new drug in the treatment of such cases.
The technical group on tuberculosis in the ministry of health has given approval to Delamanid, which is in its phase 3 clinical trials.

“We are losing a lot of patients to XDR and MDR tuberculosis. We need more than one drug for treating patients in the backdrop of increasing drug resistance in patients. Delmanid proved to be a good alternative. We will initially conduct a trial with this drug on over 400 patients in a controlled manner,” said Jagdish Prasad, director general of health services in the ministry.

“Currently, around 50% of patients don’t respond to tuberculosis treatment. Delamanid has proved effective in many clinical trials in South Africa and Japan. Taking a cue from this, we are expecting that over 70-80% patients will respond to tuberculosis treatment,” he said.”

To read the full article click here.

STREAM MDR-TB Clinical Trial: Results of comparison of 9-Month Treatment Regimen to 20-24 month regimen.

Dr. I.D. Rusen, MD, of the MRC presented the preliminary results from Stage 1 of the STREAM randomized clinical trial on Thursday, December 14th from 10:00 – 11:00 EST (16:00 – 17:00 CET; 17:00 – 18:00 SAST).

The STREAM Clinical Trial team, including Andrew Nunn and Patrick Philips (Medical Research Council’s Clinical Trials Unit at UCL) and I.D. Rusen (The Union/Vital Strategies), presented the preliminary results from Stage 1 of the STREAM randomized clinical trial. These results have been eagerly awaited and were first made public at the Union meeting last month in Guadalajara.

Presentation to be posted shortly.

 

Drug-Resistant Tuberculosis to Increase in 4 High-Burden Countries

Drug-resistant tuberculosis cases are on the rise in Russia, India, the Philippines, and South Africa and expected to increase through 2040.
Additional strategies to prevent transmission will be necessary to stop multidrug-resistant or extensively drug-resistant tuberculosis in countries with a high burden of MDR tuberculosis.
Watch the video found here to find out more.

New TB drugs are more effective and may be less toxic. Why are they still unavailable?

“The start of 2017 saw concern over a sharp increase in the rise of drug-resistant TB in South Africa. TB is killing millions each year. Last week, Médecins Sans Frontières published promising early data on the use of two new TB drugs, delamanid and bedaquiline, among patients living with drug-resistant TB in Khayelitsha, Cape Town. But availability remains the biggest concern.”

Read the full article here.

STREAM clinical trial results provide vital insight into nine-month treatment regimen for multidrug-resistant tuberculosis

“Preliminary results – released at the 48th Union Conference on Lung Health – from Stage 1 of the STREAM randomized clinical trial show that the nine-month treatment regimen being tested achieved favorable outcomes in almost 80 percent of those treated.The results suggest the nine-month regimen is very close to the effectiveness of the 20-24 month regimen recommended in the 2011 WHO guidelines, when both regimens are given under trial conditions.

The STREAM trial – initiated by The Union in 2012 with its main partner, the Medical Research Council Clinical Trials Unit at UCL, is the world’s first multi-country randomised clinical trial to test the efficacy, safety and economic impact of shortened multidrug-resistant tuberculosis (MDR-TB) treatment regimens.”

Read the full announcement here.

New Treatments for Drug-Resistant TB Get a Boost

Article by Betsy McKay, published in the Wall Street Journal, 13 Oct 2017 7:00 A.M. ET
New research released this week bolsters the case for more effective, less toxic and shorter treatment regimens for drug-resistant tuberculosis, offering hope for patients suffering from a disease that is notoriously difficult to treat.
 
The three separate studies are among several that TB researchers have under way to develop new drug combinations to replace current treatments that last as long as two years, involve up to 15,000 pills, and can cause deafness, renal failure and other debilitating effects. Many patients are never cured.
 
Findings in two of the studies suggest that the bedaquiline and delamanid, the first new drugs for TB in about 50 years, should be made more widely available, TB experts say.
 
“There is no question that these drugs should be used more widely,” said Paul Farmer, chief strategist and co-founder of Partners in Health, which is part of a consortium conducting one of the new studies being presented at the Union World Conference on Lung Health this week in Guadalajara, Mexico.
 
The new drugs have been given to fewer than 11,000 patients since bedaquiline was approved by the Food and Drug Administration nearly five years ago. That compares with an estimated 580,000 people who are infected with drug-resistant TB every year.
 
Earlier studies on the new drugs, conducted on small numbers of patients, left open the question of whether the drugs would be safe when delivered in larger numbers. Some patients in these studies developed a condition considered to be a marker for cardiac problems such as heart arrhythmias and possible sudden death.
 
The drugs were approved conditionally by some regulators such as the FDA. But the World Health Organization urged caution and recommended they be used only for patients who couldn’t be treated with certain second-line drugs.
 
In one of the new studies, researchers examined 356 patients in 15 countries who had severe forms of drug-resistant TB and were started on new drug regimens with bedaquiline or delamanid or both. They found that 82% of the patients responded to the new treatment within six months, a substantial number given that many had already tried and had no success with regimens of older drugs, said Carole Mitnick, associate professor of global health and social medicine at Harvard Medical School and Partners in Health’s director of research for the endTB project, the consortium conducting the study. There were no cardiac events, she said.
 
The consortium is also testing the new drugs in new, shorter regimens. The endTB consortium aims to expand the market for bedaquiline and delamanid with $60 million in funding through 2019 by Unitaid, an organization that invests in making drugs and diagnostics for HIV/AIDS, tuberculosis and malaria accessible. The consortium includes PIH, Doctors Without Borders, and Interactive Research & Development, a global health-delivery and -research group.
 
In the second study, the maker of delamanid, Otsuka Pharmaceutical Co., had similar results. The study found that 83.6% of patients on an existing drug regimen to which delamanid was added responded to treatment within six months, compared with 78.2% who were on the regimen without delamanid. The company says that patients on delamanid responded to treatment six to 13 days quicker. More than three-quarters of patients in both groups were cured, the company said. No cardiac events were reported.
 
The WHO will review the data on delamanid in the next couple of weeks, said Karin Weyer, coordinator of diagnostics, laboratories and drug resistance for the WHO’s Global TB Program.
 
A third trial presented at the lung conference found a nine-month regimen of existing drugs was about as effective as a two-year regimen in patients who don’t have complicated drug resistance. Trial investigators noted that it is less costly and easier on patients. The WHO began recommending the shorter regimen many drug-resistant patients last year, and Dr. Weyer said the new data provide reassurance for the WHO’s policy.

IN THE NEWS: NIH funds SLU research of possible treatment for drug-resistant TB

“Saint Louis University is leading a multi-national clinical trial of what could become a regimen for drug resistant tuberculosis that does not require injectable medications. The project is funded by a $6.4 million task order from the National Institute of Allergy and Infectious Diseases , part of the National Institutes of Health.

Saint Louis University, a member of NIAID’s network of Vaccine and Treatment Evaluation Units (VTEUs), is partnering with Aurum Institute in Johannesburg, South Africa, the University of Maryland VTEU and Makerere University in Kampala, Uganda, for the phase 4 clinical trial.

Study participants will be recruited in South Africa and Uganda, where MDR-TB is prevalent and clinical data will be analyzed by Saint Louis University and University of Maryland. Researchers will study two groups of volunteers — those who receive the standard therapy for MDR-TB and those who receive a regimen that substitutes an oral medication named delamanid for the shot. In both groups, the efficacy and safety of the tested medications will be analyzed.”

To learn more about the vaccine research being conducted at Saint Louis University, visit vaccine.slu.edu.