New Guide to Shorter Regimen for Treating DR-TB

DR-TB STAT + TAG brief: Is Shorter Better? Understanding the Shorter Regimen For Treating Drug-Resistant Tuberculosis

“Multidrug-resistant TB (MDR-TB) is a growing problem around the world, and is difficult to treat. In 2016, the World Health Organization (WHO) recommended a shorter regimen for treating MDR-TB. Now, data from a randomized controlled trial are available. The Drug-Resistant TB Treatment Scale-up Action Team (DR-TB STAT) and Treatment Action Group (TAG) released a new brief explaining what the shorter regimen is, who can receive it, and its advantages and disadvantages.”

Read the full brief here

ZeNix clinical trial announced

New trial evaluates whether the efficacy of the BPaL drug regimen can be maintained with reduced toxicity

“TB Alliance has announced the start of a clinical trial of a three-drug regimen to treat extensively drug resistant tuberculosis (XDR-TB)—one of the deadliest forms of tuberculosis (TB)—and those with pre-XDR-TB and multi-drug resident TB (MDR-TB) whose prior treatment has failed or who have not tolerated their treatment.

The trial, called ZeNix, will evaluate whether the efficacy of the BPaL (bedaquiline, pretomanid and linezolid) drug regimen can be maintained, while reducing toxicity by testing a lower dose and shorter duration of the drug linezolid. The first ZeNix patients have been enrolled in Georgia and South Africa, with sites in Russia joining later in 2018.

‘Too few people with XDR-TB are successfully cured with the current treatments,’ said Dr. Mel Spigelman, president and CEO of TB Alliance. ‘The present treatments take far too long and are made up of complex patchworks of drugs, many of which are toxic or ineffective—further contributing to TB drug resistance. With ZeNix, we are attempting to optimize a potentially safer, quicker and less complicated treatment to address this dire situation.’”

Read the full announcement 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.

J&J partners with CSIR-IMTECH on TB treatments

“The Indian subsidiary of US healthcare giant Johnson & Johnson (NYSE: JNJ) announced a new partnership with the Institute of Microbial Technology (IMTECH), part of the Council of Scientific and Industrial Research (CSIR), to unlock the potential of Indian science and help accelerate the discovery of innovative new tuberculosis (TB) treatments.

Under the Memorandum of Understanding, scientists from J&J’s global public health team will work closely with scientists from CSIR-IMTECH, based in Chandigarh, India, on a research and development program to explore potentially more effective, safer, all-oral treatment regimens to tackle multidrug-resistant TB (MDR-TB), as well as new molecular entities to treat all TB patients.

The new research program will capitalize on the CSIR-IMTECH’s world-class expertise in microbial technology and research and the proven research and development capabilities of J&J’s Janssen Pharmaceutical Companies to strengthen the collective potential of our research efforts.”

Read the Pharma Letter here.

Estimating the future burden of multidrug-resistant and extensively drug-resistant tuberculosis in India, the Philippines, Russia, and South Africa: a mathematical modelling study

“This study forecasted the percentage of MDR tuberculosis among incident cases of tuberculosis to increase, reaching 12·4% in India, 8·9% in the Philippines, 32·5% in Russia, and 5·7% in South Africa in 2040. It also predicted the percentage of XDR tuberculosis among incident MDR tuberculosis to increase, reaching 8·9% in India, 9·0% in the Philippines, 9·0% in Russia, and 8·5% in South Africa in 2040.

Acquired drug resistance would cause less than 30% of incident MDR tuberculosis during 2000-40. Acquired drug resistance caused 80% of incident XDR tuberculosis in 2000, but this estimate would decrease to less than 50% by 2040.

MDR and XDR tuberculosis were forecast to increase in all four countries despite improvements in acquired drug resistance shown by the Green Light Committee-supported programmatic management of drug-resistant tuberculosis. Additional control efforts beyond improving acquired drug resistance rates are needed to stop the spread of MDR and XDR tuberculosis in countries with a high burden of MDR tuberculosis.”

Read the full article here.

TB makes the G20 Declaration

On 7 & 8th July 2017, leaders of the G20 met in Hamburg, Germany, to address major global economic challenges and to contribute to prosperity and well-being. Their Declaration, published on July 8, carries an important section on combatting antimicrobial resistance (AMR):

“AMR represents a growing threat to public health and economic growth. To tackle the spread of AMR in humans, animals and the environment, we aim to have implementation of our National Action Plans, based on a One-Health approach, well under way by the end of 2018.

We will promote the prudent use of antibiotics in all sectors and strive to restrict their use in veterinary medicine to therapeutic uses alone. Responsible and prudent use of antibiotics in food producing animals does not include the use for growth promotion in the absence of risk analysis. We underline that treatments should be available through prescription or the veterinary equivalent only. We will strengthen public awareness, infection prevention and control and improve the understanding of the issue of antimicrobials in the environment. 

We will promote access to affordable and quality antimicrobials, vaccines and diagnostics, including through efforts to preserve existing therapeutic options. We highlight the importance of fostering R&D, in particular for priority pathogens as identified by the WHO and tuberculosis.

We call for a new international R&D Collaboration Hub to maximise the impact of existing and new anti-microbial basic and clinical research initiatives as well as product development. We invite all interested countries and partners to join this new initiative. Concurrently, in collaboration with relevant experts including from the OECD and the WHO, we will further examine practical market incentive options.”

Read the full news report from Nature Microbiology here.

Regulators in the EU, Japan, and US take steps to facilitate development of new antibiotics

The European Medicines Agency, the Japanese Pharmaceuticals and Medical Devices Agency, and the United States’ Food and Drug Administration have agreed to align their data requirements for certain aspects of the clinical development of new antibiotics in order to stimulate the development of new treatments to fight antimicrobial resistance and protect global public health.

 Representatives from the three regulatory agencies met in Vienna on 26-27 April 2017 and discussed recommendations for the design of clinical trials that test new treatments for certain types of bacterial infections, including infections caused by multi-drug resistant organisms. They identified a number of areas where the data requirements in the three regions could be streamlined. The three regulatory agencies will be working to update their guidance documents respectively.

Read the full press release here.