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.

WEBINAR: LAM as a Pharmacodynamic Biomarker and Drug Development Tool for TB

On Thursday, June 22nd from 8:30 to 9:30 EST (14:30-15:30 CEST, SAST), Dr. Yongge Liu, Director of Diagnostics at Otsuka Novel Products, gave a presentation on LAM (Lipoarabinomannan) as a Pharmacodynamic Biomarker and Drug Development Tool for TB

Otsuka Pharmaceutical is developing an assay that can measure the concentration of LAM, which is showing promise as a biomarker of the load of viable tubercle bacilli in sputum. The assay shows potential for real-time evaluation of treatment response in clinical trials, and Otsuka is working with the Critical Path to TB Drug Regimens (CPTR) to seek qualification of this biomarker as a drug development tool by the FDA in the USA and as a drug development method by the EMA in the European Union. Yongge Liu, the Director of Diagnostics at Otsuka Novel Products, will discuss the development of this assay and the biomarker qualification process.

A copy of the presentation slides can be viewed here.

Blocking TB germs’ metabolic ‘escape pathways’ may be key to better, shorter treatment

New research suggests the bacteria that cause tuberculosis alter their metabolism to combat exposure to antimicrobials, and that these metabolic “escape pathways” might be neutralized by new drugs to shorten the troublesome duration of therapy. Researchers studied the proteomic responses of the bacteria to five compounds – isoniazid, rifampicin, moxifloxacin, mefloquine and bedaquiline – and discovered escape pathways and enzymes associated with changes in metabolic state.

“When we looked at the enzymes carefully, we realized the enzymes being synthesized by the bacteria were enzymes connecting several different metabolic pathways,”Oregon State University scientist Luiz Bermudez said. “Then we came up with the idea that maybe what the bacteria were trying to do, in the presence of a bactericidal compound that was threatening their way of living, was use other ways to survive. One of the things we saw, for example, was a shift to an anaerobic metabolism, which makes a lot of drugs inactive and incapable of killing bacteria. “The gene inactivation of some of these enzymes results in improved drug efficacy against Mtb,” he said. “The identified proteins may provide powerful targets for development of synergistic drugs aimed to accelerate bacterial killing.”

Read the full statement here.

Population implications of the use of bedaquiline in people with extensively drug-resistant TB: are fears of resistance justified?

 In a Personal View published in The Lancet Infectious Diseases, Amber Kunkel, Jennifer Furin and Ted Cohen argue that resistance concerns should not forestall use of bedaquiline in patients with XDR-TB. Their position in favour of increased access to bedaquiline for these patients is based on three arguments. First, the use of drug combinations that include bedaquiline might prevent spread of XDR disease to others in the community. Second, until new combination regimens of novel drugs for XDR-TB become available, patients with XDR disease and their infected contacts will face equivalent outcomes if bedaquiline is either not provided because of policy, or not effective because of resistance. Finally, because resistance to bedaquiline and other antituberculosis drugs is caused by mutations within a single bacterial chromosome, use of bedaquiline in patients with XDR-TB will not substantially increase the risk of bedaquiline resistance in patients with drug-susceptible or multidrug-resistant (non‑XDR) tuberculosis strains.
Read the full Personal View here.

EU leaders seek new tools against drug-resistant TB

Leaders from the governments of France and the Netherlands today urged funding for new treatment and prevention tools against drug-resistant tuberculosis at a high-level meeting in Brussels, citing the scope of the problem in Europe.

“Because of drug resistance, TB is evolving to become an untreatable disease for a growing number of people,” said Michèle Boccoz, Special Ambassador for fighting against HIV/AIDS and communicable diseases at the French Ministry of Foreign Affairs and International Development. “Investment in research and development now will allow us to have the drugs and vaccines at hand to eventually end the threat of TB as a health problem in Europe.”

“Without tools such as new drugs and vaccines, we know we cannot reach our goals for controlling TB,” said Marja Esveld, senior policy advisor, global health from the Dutch Ministry of Health. “Now is the time to step up the resources to ensure we have the means to effectively end the epidemic and address the emerging threat of drug-resistant TB.”

Read the article here.