Category: Respiratory Diseases

Categories : New Compounds and Treatments Respiratory DiseasesTags : Leave a comment

Excitement Builds for Long-acting TB Treatments, but Research Still at Early Stage

On By ModernMedia
Mycobacterium tuberculosis drug susceptibility test. Photo by CDC on Unsplash

By Catherine Tomlinson

Both TB treatment and TB preventive therapy involve taking lots of pills, usually for several months. Researchers are working on new long-acting formulations that might, for example, reduce an entire course of TB preventive therapy to a single injection.

The biggest HIV news of last year was that an injection containing an antiretroviral called lenacapavir provides six months of protection against HIV infection per shot. While it will be several years before the jabs become widely available, experts nevertheless hailed the development as a potential game-changer. In some countries, HIV treatment is already available as injections – containing the antiretrovirals cabotegravir and rilpivirine  – administered every two months.

Scientists working on tuberculosis (TB) are trying to replicate the successes of the HIV field and develop similarly long-acting formulations of TB medicines. The good news is that they have several exciting products under development – the bad news is that the research is still at a very early stage and the pivotal studies that will tell us if these products work are likely still years away.

But if they work, they could make a big difference to patients. That is because TB treatment and TB preventive therapy mostly still requires swallowing lots of pills over a long period of time. There is some good evidence that many people would prefer long-acting injections.

The case for long-acting TB medicines

TB preventive therapy is used to stop someone suspected of having latent TB infection from falling ill with TB. In South Africa, such preventive therapy is recommended for all close contacts of someone sick with TB. Typically, it involves taking tablets for three or six months (a one-month course has been shown to work, but is not widely available). There is research that shows that the shorter the regimen the more likely it is to be completed.

The hope is that a long-acting product might do away with swallowing tablets altogether and reduce an entire course of preventive therapy to a single injection. This is likely to be more convenient for patients as well as come with the benefit of perfect treatment completion rates.

TB preventive therapy is a simpler target for long-acting formulations than TB treatment since it typically involves only one or two drugs and treatment durations are shorter. TB treatment typically takes six or more months to complete and usually involves taking four different drugs – often four for two months and then only two for the remaining four months in what is called the continuation phase. Some of the current thinking is that the continuation phase could potentially be replaced by long-acting formulations of TB medicines. This could shorten the duration of TB treatment to just two months of taking tablets.

Not an easy nut to crack

As explained by Dr Eric Nuermberger of Johns Hopkins University, not all TB medicines available as tablets make good candidates for translation to long-acting injectable formulations. He was presenting on long-acting TB drugs at the Conference for Retroviruses and Opportunistic Infections (CROI), recently held in San Francisco.

Nuermberger outlined three key characteristics that are needed for long-acting formulations. These are low water solubility (so the drug doesn’t dissolve to quickly), low clearance in plasma (so that the body doesn’t clear the drug too quickly), and high drug potency (so that a small volume of drug can be effective for a long period of time).

One key challenge, according to Nuermberger, is that scientists do not yet have reliable biomarkers to measure the effectiveness of long-acting TB preventive therapy in phase II trials. Biomarkers, such as blood levels of certain proteins, could in theory offer scientists a faster way to assess if TB preventative therapy is working, without having to monitor clinical trial participants for long periods of time to determine treatment outcomes.

Writing in the journal Clinical Infectious Diseases, scientists working to develop long-acting TB products explained: “The inability to culture or otherwise quantify viable bacteria during latent TB infection and the lack of validated surrogate biomarkers mean that there is no opportunity to obtain initial proof of efficacy… which is usually the domain of phase 2 trials. Instead, the development of new TPT regimens requires bridging directly from preclinical studies and phase 1 trials to phase 3 trials, which are themselves long and require large numbers of participants.”

However, they added that “[t]he search for biomarkers that act as prospective signatures of risk for developing TB disease is a very active research area and an important scientific priority for the field”.

Back at CROI, Nuermberger also told participants that most products in the pipeline remain at pre-clinical stages and are still being tested in mice. He explained that differences in how depot drugs — drugs released slowly over time — work in mice and humans make it hard to apply findings from mice to humans. But modeling is being done to help bridge this gap.

‘Expanded remarkably’

Despite these challenges, Nuermberger said “the number of long-acting drug formulations in development [for TB] has really expanded remarkably in the last few years, which is a very promising development”.

The product that is furthest along in the development pipeline, but still at a very early stage of research, is a long-acting form of bedaquiline. This drug is currently used for the treatment of drug-resistant forms of TB and falls in a class of antibiotics known as diarylquinolines.

The Belgian pharmaceutical company Janssen is currently running a phase I trial of long-acting injectable bedaquiline in Austria. Phase I trials are conducted in a small group of healthy individuals to assess the safety and tolerability of an experimental medicine. In the phase 1 bedaquiline trial, researchers are investigating the safety and tolerability of different doses of long-acting injectable bedaquiline.

Several other long-acting TB medicines are being investigated in preclinical research, including long-acting versions of the TB medicines rifabutin and rifapentine, as well as the second generation diarylquinolines, TBJ-876 and TBA-587, which are under development by the TB Alliance. The second generation diarylquinolines are being tested on their own and in combination with pretomanid and telacebec.

In addition, the University of Liverpool, Johns Hopkins University, University of Southern Denmark, University of North Carolina and the US pharmaceutical company Inflamamasome Therapeutics, are all involved in pre-clinical research on long-acting formulations. These efforts are supported financially by Unitaid, the US National Institutes of Health, and the Gates Foundation.

The treatments being developed include aqueous nanoparticle suspensions, in-situ forming implants, and rod implants. Aqueous nanoparticle suspensions are drugs turned into tiny particles and delivered in a water-based solution via injection. In-situ forming implants are injected as a liquid that then solidifies into an implant under the skin. Rod implants are small, rod-shaped devices inserted under the skin with a needle-like tool after numbing the area with a local anaesthetic.

What users prefer

At CROI, delegates also learned about patient and provider preferences for long-acting TB treatment.

Dr Marcia Vermeulen from the University of Cape Town presented the results of a survey involving over 400 patients in South Africa and India, as well as 94 healthcare providers.

Seventy-five percent of healthcare workers said they would prescribe a long-acting injectable product rather than pills for tuberculosis preventative therapy if it was priced the same or lower. Similarly, 75% of patients said they would try an injectable product for TB prevention if it became available.

“As a TB survivor, I am excited about long-acting TB treatment as it doesn’t require frequent facility visits, saving a person’s time and money, and can thereby increase adherence and improve treatment outcomes,” TB Proof’s Phumeza Tisile told Spotlight.

She added that communities should be at the heart of rollout plans because they understand the needs of people affected by TB and know how to communicate effectively to encourage involvement and adoption.

Disclosure: The Gates Foundation is mentioned in this article. Spotlight receives funding from the Gates Foundation but is editorially independent – an independence that the editors guard jealously. Spotlight is a member of the South African Press Council.

Republished from Spotlight under a Creative Commons licence.

Read the original article.

Categories : Hospitals Respiratory DiseasesTags :

Global Action Needed to Solve the Medical Oxygen Crisis

On By ModernMedia
Photo by engin akyurt on Unsplash

Targets for universal access, national roadmaps and more affordable and accessible care are vital to help fill the medical oxygen gap affecting more than half of the world’s population, according to a new global report.

The Lancet Global Health Commission report details for the first time how future investment in strengthening medical oxygen systems could have a huge impact by saving millions of lives and improving pandemic preparedness.

Almost 400 million children and adults require medical oxygen every year. More than five billion people, 60 per cent of the world’s population, don’t have access to safe and affordable medical oxygen services.

The Commission, co-chaired by Makerere University in Uganda, the International Centre for Diarrheal Disease Research (icddr,b) in Bangladesh, Murdoch Children’s Research Institute (MCRI) in Australia, Karolinska Institute in Sweden and the Every Breath Counts Coalition in the US was launched in 2022 against the backdrop of the COVID-19 pandemic. The Commission was tasked with submitting actionable recommendations for governments, industry, global health agencies, donors and the healthcare workforce.

MCRI Dr Hamish Graham said the COVID-19 pandemic had put a spotlight on the longstanding global inequities in accessing medical oxygen.

“Oxygen is required at every level of the healthcare system for children and adults with a wide range of acute and chronic conditions,” he said. Previous efforts, including the major investments in response to the COVID-19 pandemic, largely focused on the delivery of equipment to produce more oxygen, neglecting the supporting systems and people required to ensure it was distributed, maintained, and used safely and effectively.”

Dr Graham said channelling investments into national oxygen plans and bolstering health systems, including wider use of pulse oximeters (a small device that measures how much oxygen is in the blood), would help solve the medical oxygen crisis.

“We urgently need to make high-quality, pulse oximeters more affordable and widely accessible,” he said. Pulse oximeters are available in 54 per cent of general and 83 per cent of tertiary hospitals in low- and middle-income countries, with frequent shortages and equipment breakdowns.

“Concerningly, in these countries the devices are performed for only 20 per cent of patients presenting to general hospitals and almost never for those at primary healthcare facilities. We see the greatest inequities in small and rural government health facilities and across Sub-Saharan Africa.”

Dr Graham said the importance of medical oxygen must also be recognised and integrated into broader national strategies and pandemic preparedness and response planning.

“Governments should bring together public and private sector partners with a stake in medical oxygen delivery, including health, education, industry, energy and transport to design a system and set up a governance structure that supports the new Global Oxygen Alliance (GO₂AL) and replenishing The Global Fund with a strong oxygen access mandate,” he said.

Source: Murdoch Childrens Research Institute

Categories : Respiratory DiseasesTags :

Cystic Fibrosis Damages the Immune System Early on

On By ModernMedia
Photo by Robina Weermeijer on Unsplash

Despite new medication, cystic fibrosis often leads to permanent lung damage. Working with an international team, researchers from the Technical University of Munich (TUM) have discovered that the disease causes changes in the immune system early in life, presumably even in newborns. These changes lead to frequent inflammation and are not affected by drugs targeting the altered mucus production.

Cystic fibrosis is caused by hereditary genetic mutations that impair or halt the production of the CFTR protein. The respiratory tract is most severely affected. There, the mucus becomes so viscous that pathogens like bacteria cannot be removed by coughing. The result is often a deadly cycle of infection and inflammation.

In recent years, doctors have started using so-called CFTR modulator therapies to enhance the protein’s function. This reduces mucus formation and significantly improves the quality of life for those affected. However, clinical studies show that airway inflammation continues to occur frequently. In older patients, the decline in lung function seems unstoppable.

Current research aims to uncover additional processes in cystic fibrosis. “We specifically looked at how the immune system behaves in cystic fibrosis before the cycle of infection and inflammation begins,” said Prof. Nikolai Klymiuk from TUM. He is part of the international team that recently published a study on cystic fibrosis in Science Translational Medicine.

Immature immune cells in blood samples from children

The researchers found that in blood samples from children with cystic fibrosis and biological material from pigs with the same genetic defect, certain cells of the innate immune system are immature. This makes them less effective at fighting bacteria. Pigs with cystic fibrosis also showed an increased number and significantly altered composition of immune cells in the lungs at birth. The strong resemblance between the immune systems of pigs and humans suggests that this finding likely applies to human patients as well.

‘Emergency program’ responsible?

According to the authors, one possible explanation for the changes in the immune system could be a kind of “emergency program”. The program stimulates the body to produce a large number of immune cells particularly quickly or over a longer period of time. One consequence is the formation of immature immune cells, which could contribute to the fatal cycle of infections and inflammation in cystic fibrosis: Although immune cells are present in the lungs, they are ineffective and cause damage to the lung tissue without preventing infections in the long term.

Since immune cells generally produce only very small amounts of CFTR, the research team believes that the influence of cystic fibrosis on the immune system is indirect. This could explain why defective immune reactions cannot be treated well with novel CFTR modulator therapies.

Changes not a result of frequent infections

“We don’t yet know exactly why the immune cells in cystic fibrosis show such changes,” says Nikolai Klymiuk, Professor of Cardiovascular Translation in Large Animal Models. “However, we can show that these occur early in life. They then persist in the further course of life.” According to Klymiuk, although altered immune cells were known from blood samples of adults with cystic fibrosis, they were seen as a consequence of the numerous infections.

“To enable people with cystic fibrosis to live without symptoms, we probably need to tackle the disease on several levels,” said Klymiuk. “We hope our work will help us better understand the causes of the defective immune system and correct them in the future”

Source: Technical University of Munich (TUM)

Categories : Environmental Effects Respiratory DiseasesTags :

Air Pollution Linked to More Lower Respiratory Infection Hospital Admissions

On By ModernMedia
Photo by Kouji Tsuru on Pexels

Air pollution is a well-known risk factor for respiratory diseases such as asthma and chronic obstructive pulmonary disease (COPD) – but its contribution to lower respiratory infections is less well known, especially in adults. To address this, a team from the Barcelona Institute for Global Health (ISGlobal), a centre supported by the ”la Caixa” Foundation, assessed the effect of air pollution on hospital admissions for lower respiratory infections in adults, and which subgroups that could be particularly vulnerable to these infections. The results have been published in the journal Environment International.

The research shows that long-term exposure to particulate matter (PM2.5 and PM10), nitrogen dioxide (NO2) and ozone (O3) air pollution is associated with more hospital admissions for lower respiratory tract infections in adults. The associations were stronger in men, people over 65 years of age and those diagnosed with hypertension.

The study involved 3 800 000 adults from the COVAIR-CAT cohort, a large cohort of 7.7 million people based on the health system of Catalonia. The research team used exposure models to estimate annual average concentrations of PM2.5, PM10, NO2 and ozone during the warm season (May-September) between 2018 and 2020 at the participants’ residences. Information on hospital admissions, mortality and comorbidities was obtained from various administrative databases. The study included hospital admissions for all lower respiratory infections and, separately, the subgroup of hospital admissions for influenza and pneumonia. A statistical model was then used to assess the association between air pollution and hospital admissions.

“The association between air pollution and hospital admissions for lower respiratory tract infections was observed even at pollution levels below current EU air quality standards,” says Anna Alari, ISGlobal researcher and first author of the study. “It is crucial to adopt stricter air quality standards, as more ambitious measures to reduce air pollution would decrease hospital admissions and protect vulnerable populations,” she adds.

Stronger association in men and people over 65

The association between air pollution and hospitalisations for lower respiratory tract infections was more pronounced in people over 65 years of age or with comorbidities, compared with younger people or those without comorbidities. Specifically, elevated levels of air pollution were associated with approximately three times higher rates of hospital admissions for lower respiratory infections among people aged 65 years and older compared with younger people.

In addition, exposure to elevated levels of NO2, PM2.5 or PM10 (but not O3) was associated with about a 50% increase in hospital admissions in men, while the association was about 3% higher in women.

The team observed the same pattern for hospital admissions for influenza or pneumonia, but with smaller associations compared to lower respiratory infections. “This may be due to the influence of available vaccines against the pathogens responsible for influenza and most cases of pneumonia,” says Cathryn Tonne, senior author of the study.

Source: Barcelona Institute for Global Health (ISGlobal)

Categories : Antibiotics Respiratory DiseasesTags :

Study Finds Three New Safe, Effective Ways to Treat Drug-resistant TB

On By ModernMedia
Tuberculosis bacteria. Credit: CDC

An international clinical trial has found three new safe and effective drug regimens for tuberculosis that is resistant to rifampin, the most effective of the first-line antibiotics used to treat TB. The research, published in the New England Journal of Medicine, was led by researchers at Harvard Medical School and other members of the endTB project.

The newly identified regimens take advantage of recently discovered drugs to expand the treatment arsenal and give physicians new ways to shorten and personalise treatment, minimise side effects, and treat patients using only pills instead of daily injections. They also offer alternatives in case of drug intolerance, medication shortages or unavailability, or drug resistance, the researchers said.

The endTB trial is one of four recent efforts to use randomised controlled trials to test new, shorter, less toxic regimens for drug-resistant TB. endTB uses two new drugs – bedaquiline and delamanid — which, when brought to market in 2012-2013, were the first new TB medicines developed in nearly 50 years.

To find shorter, injection-free drug combinations for people infected with TB resistant to rifampin, endTB tested five new, all-oral 9-month regimens using the two new drugs in combination with older medications.

A third drug, pretomanid, received emergency authorisation from the FDA for specific use within a regimen against highly drug-resistant TB in 2019, after the endTB clinical trial was underway, and is not included in the regimens used in these trials.

Trial regimens were considered effective if they performed at least as well as the control group, which received a well-performing standard of care composed in accordance with a stringent interpretation of World Health Organization (WHO) recommendations.

The three successful new regimens were successful for between 85 and 90% of patients, compared with 81% success for people in the control group. The control group was treated with longer treatments, which also included the recently discovered medicines.

The trial launched in 2017 and enrolled 754 patients across seven countries: Georgia, India, Kazakhstan, Lesotho, Pakistan, Peru, and South Africa. The goal was to improve treatment for patients with tuberculosis resistant to rifampin. The WHO estimates that some 410 000 people become sick with rifampin-resistant TB each year, including people who have multidrug-resistant TB (MDR-TB). Only 40% are diagnosed and treated, 65%of them successfully.

The study population included children as well as people infected with HIV or hepatitis C, both common in populations with high rates of TB. In another innovation, women who became pregnant while on treatment were included in the endTB trial. These groups are often excluded from clinical trials. In a special report published in August 2024, the WHO added the three noninferior regimens from the endTB trial to the list of treatment options for rifampin-resistant and multidrug-resistant TB (MDR-TB) treatment; the recommendations extend to these neglected groups as well as to pregnant women.

With recent efforts to end patent exclusivity on bedaquiline, two of the endTB regimens and the WHO-recommended pretomanid-containing regimen can all be purchased for less than $500, an access target set by activists more than 10 years ago, which has only just now been achieved. All of these innovations together mean the new shortened, all-oral regimens are available to more people than ever.

Source: Harvard Medical School

Categories : Antibiotics Respiratory DiseasesTags :

Short-course Antibiotics are Game-changers for Healthcare

On By ModernMedia
Photo by Marcelo Leal on Unsplash

Antibiotic overuse is a key driver in the rise of antimicrobial resistance (AMR), a major global health crisis. Researchers from the Yong Loo Lin School of Medicine, National University of Singapore (NUS Medicine) and Duke-NUS Medical School have provided compelling evidence that short-course antibiotic treatments can be a game-changer in tackling ventilator-associated pneumonia (VAP), a serious infection common in critically ill patients.

The findings from the landmark REGARD-VAP trial, published in Lancet Respiratory Medicine, and the accompanying economic analyses published in Lancet Global Health, highlight how prudent antibiotic use can curb resistance, effectively safeguarding patients as well as combatting the global threat of antimicrobial resistance while reducing healthcare costs.

Led by the NUS Medicine research team, the clinical trial examined over 450 patients across intensive care units (ICUs) in Singapore, Thailand, and Nepal. Results revealed that short-course antibiotics. carefully tailored to individual patients’ recovery, are just as effective as traditional longer treatments in preventing death and recurrence of pneumonia. “By shortening the duration of antibiotics, we can reduce the risks of side effects and resistance without compromising patient outcomes,” added Dr Mo Yin, Junior Academic Fellow at the Department of Medicine, NUS Medicine, and principal investigator of the clinical trial, and co-author of the economic analysis.

The economic analyses accompanying the trial were just published in the prestigious journal Lancet Global Health. They demonstrated that adopting short-course antibiotics offers significant value for healthcare systems. In Singapore, the strategy is cost-saving, reducing hospital expenditure while maintaining excellent outcomes for patients. In Thailand and Nepal, short-course antibiotics were highly cost-effective, with health gains outweighing the modest additional costs incurred. “Short-course antibiotics are a pragmatic solution that benefits patients and healthcare systems alike, particularly in resource-limited settings,” said Assistant Professor Yiying Cai, lead researcher from the Health Services and Systems Research Programme at Duke-NUS.

The REGARD-VAP study’s findings have practical implications for hospitals worldwide. Short-course antibiotics can streamline treatment in ICUs, where managing infections efficiently is vital. The approach is effective across high-income (Singapore), middle-income (Thailand), and low-income (Nepal) settings, making it a scalable solution for diverse healthcare systems. These results provide robust evidence including cost-effectiveness data for policymakers to adopt short-course antibiotics into national and institutional guidelines.

The team hopes to disseminate their findings globally to encourage the adoption of short-course antibiotics, particularly in regions with limited resources. They also advocate for integrating cost-effectiveness studies into future clinical trials to strengthen both clinical and economic decision-making processes. By reducing unnecessary antibiotic exposure, short-course treatments help preserve the effectiveness of existing drugs for future generations. Every additional day of antibiotic use increases the risk of drug resistance by 7%. Reducing treatment duration is a critical step in combating this silent epidemic. “Prudent antibiotic use is essential to combat antimicrobial resistance and optimise healthcare outcomes. Our findings make a strong case for adopting short-course antibiotics as the new standard of care,” concluded Dr Mo Yin.

Source: National University of Singapore, Yong Loo Lin School of Medicine

Categories : Ethics and Law Respiratory DiseasesTags :

Activists Furious after Competition Commission Drops Probe into Pharma Company

On By ModernMedia

Life-saving drugs still not available to many cystic fibrosis patients

Photo by Robina Weermeijer on Unsplash

By Tania Broughton

Health campaigners have slammed a decision by the Competition Commission to end its investigation into Vertex Pharmaceuticals’ monopoly on life-saving medicines for people living with cystic fibrosis.

“We are concerned that the Commission has fallen victim to Vertex’s well-known and aggressive PR and legal strategy, designed to safeguard its global patent monopoly at all costs,” said a statement by nine organisations: the South African Cystic Fibrosis Association, Right to Breathe Campaign, Health Justice Initiative, Vertex Save Us, Just Treatment, SECTION27, Treatment Action Campaign, People’s Health Movement and Cancer Alliance.

The Commission, in a statement released on 11 December, said it had initiated the probe against Vertex based on allegations that it was engaging in exclusionary practices and excessive pricing in the provision of Kalydeco, Orkambi, Symdeko and Trikafta – medicines used to treat cystic fibrosis.

“Following the Commission’s investigation and various engagements with Vertex, Vertex gave formal undertakings to the Commission to continue to make Trikafta available in South Africa through Section 21 of the Medicines and Related Substances Act, which enables the sale of unregistered drugs within South Africa,” it said.

This undertaking, it said, had resulted in a “non referral” of all allegations against the company.

It said that Trikafta had broadly replaced the use of the other medicines. Previously patients with cystic fibrosis had to import it. To reduce the financial burden, Vertex had from April this year begun supplying it through a local distributor.

“This makes Trikafta available locally at prices that enable cystic fibrosis patients to access treatment. Separately, financial assistance is available through a patient assistance programme managed by a non-government organisation, and eligible cystic fibrosis patients who belong to certain medical schemes get Trikafta at no cost as they also receive some financial assistance from their medical aid schemes.”

Unavailable

But health campaigners are not happy They say for the vast majority of cystic fibrosis patients (about 63%), nothing has changed.

“The real victims of this decision by the Commission are the most vulnerable South African children and young people who rely on the public health sector, who are not rich, and who have little or no medical scheme cover,” they said.

“These patients do not currently, and will not get access to this medication because of Vertex’s patents and secretive, limited access and excessive pricing strategies.”

Alarmingly, they said, the medicine remains unregistered in South Africa, forcing patients to either import it or rely on the “administratively burdensome” section 21 approval process.

“This is not a sustainable way to address a chronic treatment need,” they said.

The so-called patient assistance programme did not promote equity, was far from transparent, nor sustainable and the price was undisclosed.

They said they were seeking an urgent meeting with the Commission

“We cannot allow the manipulation of South Africa’s laws, regulations and health system to go unchecked in the name of one drug company’s self-interested monopoly greed.”

Vertex replies

Approached for comment, Vetex said more than 180 cystic fibrosis patients were accessing the medicine through the Section 21 pathway “which represents about 50% of the eligible population”.

“We took this pathway because we strongly believe that this is the fastest and most efficient route to sustainable access in South Africa, given that it does not require a regulatory filing, which can take many years.”

The company said even with regulatory approval, most novel, high value medicines were not included on the Prescribed Minimum Benefits list.

“There is therefore no obligation for funders [private and public health insurances] to reimburse the costs of these medicines, which effectively make them inaccessible to most patients. In our opinion, a license application would not speed up the process for broad access to our cystic fibrosis medicines.”

It said its triple combination therapy was currently funded by eleven healthcare providers, who cover most cystic fibrosis patients in the private sector in the country.

“We are continuing discussions with other health insurers and are in parallel exploring potential sustainable access opportunities in the public sector, which has been historically challenging for rare disease medicines in South Africa.”

It said “exact pricing” and details of its partnerships remained confidential.

Republished from GroundUp under a Creative Commons Attribution-NoDerivatives 4.0 International License.

Read the original article

Categories : Antibiotics Respiratory DiseasesTags :

Tuberculosis Strains Resistant to New Drug Regimen are Being Transmitted between Patients

On By ModernMedia
Mycobacterium tuberculosis drug susceptibility test. Photo by CDC on Unsplash

Multidrug-resistant tuberculosis (MDR-TB) poses a particular threat to global health. A study led by the Swiss Tropical and Public Health Institute (Swiss TPH) shows that resistance to the new MDR-TB treatment regimen recently recommended by the World Health Organization is already spreading between patients. The findings, published in NEJM, highlight the urgent need for better surveillance and infection control to counteract the rise in antimicrobial resistance.

The traditional treatment regimen for MDR-TB is lengthy, expensive, and comes with severe adverse event. In 2022, the World Health Organization (WHO) endorsed a new 6-month regimen, the BPaL(M), based on evidence of its improved safety and efficacy from numerous clinical studies, including TB-PRACTECAL.

Monitoring the implementation of a new treatment regimen

“While this new regimen is a game changer for patients suffering from MDR-TB, we knew that it will be difficult to outsmart Mycobacterium tuberculosis, the bacteria causing TB,” said Sébastien Gagneux, Head of the Department Medical Parasitology and Infection Biology at Swiss TPH and senior author of the study. “It was therefore crucial to study how the TB bacteria would react to the global roll-out of this new regimen.”

This new study led by Swiss TPH in collaboration with the National Centre for Tuberculosis and Lung Diseases in Tbilisi, Georgia, now examined in detail whether resistance to the drugs in the new regimen has already emerged since its introduction, and whether this resistance is transmitting between patients.

Over a quarter of resistant strains result from transmission between patients

The researchers analysed the genomes of close to 90 000 M. tuberculosis strains from Georgia and many other countries around the world. They identified a total of 514 strains that were resistant to TB drugs, including both the old and the new treatment regimens. These highly drug-resistant strains were found in 27 countries across four continents.

Alarmingly, 28% of these strains were transmitted directly from one patient to another. “We already had anecdotal evidence of resistance emerging to the new regimen, but we did not know to what extent transmission was responsible for the spread of these highly drug-resistant strains,” said Galo A. Goig, postdoctoral collaborator at Swiss TPH and first author of the study.

“The good news is that the total number of these cases is still low. However, the fact that more than a quarter of these highly drug-resistant cases are due to patient-to-patient transmission, only two years after WHO endorsed the new regimen, is worrying,” added Goig.

Call for better surveillance and infection control

These findings have important implications for public health policy and interventions. “These new drugs have taken many years to develop, and to prevent drug resistance from emerging, it is essential to combine the deployment of these new regimens with robust diagnostics and surveillance systems,” said Chloé Loiseau, postdoctoral collaborator at Swiss TPH and co-author of the paper.

The authors emphasise the need for improved diagnostic tools, better infection control and robust surveillance systems to curb the spread of these highly drug-resistant strains, and to safeguard the efficacy of the new treatment regimen.

Tackling antimicrobial resistance

While there are already new TB drugs in the pipeline, experts worry that M. tuberculosis will continue to find ways to evade new drugs. “The example of these highly drug-resistant TB strains further illustrates that antimicrobial resistance is one of the most critical threats to global health today,” said Gagneux. “We must stay ahead in this constant race between drug development and bacterial resistance, and take proactive steps to prevent a ‘post-antibiotic era’ for TB and other diseases.”

Source: Swiss Tropical and Public Health Institute

Categories : Medical Industry Respiratory DiseasesTags :

Pretoria Company Aims to Lead SA in Making Key TB Drug Ingredients

On By ModernMedia
Source: Unsplash CC0

By Catherine Tomlinson

Though several South African companies are producing HIV and TB medicines, the active ingredients that go into these medicines are usually imported from India or China. Now, a local company is planning to break new ground by making the active ingredients for two important TB medicines in Pretoria. We zoom in on the company’s efforts and outline some of the obstacles to getting such local production off the ground.

South Africa has a relatively robust pharmaceutical sector. Approximately 60% of the medicines sold in South Africa are locally produced, according to Dr Senelisiwe Ntsele, writing in an opinion piece for the Department of Trade, Industry and Competition (dtic).

But most of the time we are not producing these medicines from scratch. In fact, like most countries in the world, we mostly import the ingredients that make the medicines work – commonly referred to as active pharmaceutical ingredients, or APIs. In addition to APIs, medicines contain other inactive substances that maintain their form and structure and assist in their delivery: such as binders, stabilisers, and disintegrants.

Around 98% of the APIs used in locally formulated medicines are imported and South Africa spends around R15 billion a year importing APIs, according to Ntsele.

Government has tried to address South Africa’s dependence on imported APIs as part of its broader strategy to bolster the local pharmaceutical industry, which is identified as a priority sector for investment in the country’s Industrial Policy Action Plan. Several government departments provide support to the local pharmaceutical sector, including for local establishment of API manufacturing capacity. These departments include the dtic, the Department of Science and Innovation (DSI), the Technology Innovation Agency (TIA), and the Industrial Development Corporation (IDC) – South Africa’s development finance instrument.

In a bid to reduce the country’s reliance on imported APIs, Ketlaphela – a state-owned API manufacturing company – was announced in 2012. The plan was that Ketlaphela would produce APIs used in HIV medicines, but after multiple setbacks the initiative never got off the ground. Spotlight reported on the history of Ketlaphela in more detail here.

Turning to the private sector

Less well known than Ketlaphela, are government’s efforts to support API manufacturing capacity in the private sector. One private company that has received such government support and seem set to start delivering is Pretoria-based Chemical Process Technologies Pharma (CPT Pharma) that was established in 2014.

CPT Pharma is a subsidiary of Chemical Process Technologies, a company with many years of experience in chemical manufacturing and synthesis, including manufacturing of APIs for animal medicines. Human medicines, CPT Pharma’s core business, have stricter production management and quality control standards than those for animal medicines.

Dr Hannes Malan, Managing Director of CPT Pharma, told Spotlight that the company has 14 APIs in its pipeline, with a strong focus on TB medicines.

CCPT Pharma is a subsidiary of Chemical Process Technologies. (Photo: Supplied)

In 2023, the company secured a license from USAID to produce API for rifapentine, a drug widely used for TB prevention, and in 2022 they secured a licence from the Medicines Patent Pool to produce API for molnupiravir, a treatment for COVID-19. Malan pointed out that these two licenses were agreed with organisations aiming to expand the presence of API manufacturers in Africa – unlike typical arrangements driven by pharmaceutical companies looking to secure their own supply chains.

“For all the other APIs that we’re working on [beyond molnupiravir and rifapentine], we’re either working on technical packs [technical information about the API] that were available in the public domain or technologies that we’ve developed ourselves,” said Malan.

“Our approach has always been to look at the molecules, look at the market value, look at the technology, and then see if there’s an opportunity for us to develop technology that allows us to produce these compounds cost competitively,” he said.

“We really believe that to be competitive and independent, you have to have your own technology. Doing a technology transfer from Big Pharma does not make you independent,” Malan added.

How to fund it all?

In 2017, the company completed a pilot plant for making APIs. Then in 2020 it received approval from the South African Health Products Regulatory Authority (SAHPRA) to produce APIs for human use. The plant was built for R50 million, funded jointly by the IDC, TIA, and CPT Pharma.

Malan said that that the IDC and TIA also supported trial runs to test CPT Pharma’s manufacturing processes and technology. These tests included several APIs in development, such as isoniazid, a drug commonly used to prevent and treat TB.

The company has also secured funding from several international donors. The Gates Foundation provided support to develop manufacturing technology for the anti-malarial drug amodiaquine, as well as tuberculosis medicines bedaquiline and pretomanid. GIZ, a German development agency involved in a European Union project to boost vaccine and health product production in Africa, supported the company’s work on molnupiravir and dolutegravir – a widely used HIV medicine. USAID and the DSI are supporting the company’s work on developing rifapentine API manufacturing capacity.

Most of this financial support has been in the form of grants.

Still building new plants

While CPT Pharma has secured local and international funding to help construct a pilot plant and to develop its API manufacturing technology and processes, Malan said more investment is needed to support the construction of two commercial-scale manufacturing facilities: an isoniazid API manufacturing plant and a multiple API manufacturing facility.

Construction of the isoniazid manufacturing plant has already commenced using existing land and infrastructure with support from the IDC, but it is short of around R20 million to complete it, said Malan.

Although the plant is not yet operational, he said a company has already expressed interest in buying CPT Pharma’s locally produced isoniazid API. This company, said Malan, is contracted to supply isoniazid to government. The plan is to initially supply the company with isoniazid API produced at its pilot plant

Malan said the commercial plant, when built, will be able to manufacture enough isoniazid API to supply around 60% of local demand.

Things are less far down the road with plans for a plant to produce multiple different APIs at commercial scale, and more work is needed to understand the financing requirements for this type of facility, said Malan. “We want to do a bankable study and a concept design for such a plant,” he said. Based on CPT Pharma’s own experience, published data, and the required complexity and capacity of the plant, Malan said it is estimated that construction for the multi-API plant will cost around US$100 million or R1.8 billion.

Plans to commercialise

Meanwhile, the company is moving forward with plans to commercialise isoniazid and rifapentine API from its pilot plant. Isoniazid and rifapentine is increasingly used together as TB preventive therapy.

“For rifapentine, our pilot plant is seen as the commercial plant,” said Malan. “At this stage, we can use the pilot facility and the pilot reactor to produce enough rifapentine to get into the market and to grow the market.” But in the long term he said the company hopes to transfer rifapentine manufacturing to a larger commercial plant.

The company is also planning to apply for World Health Organization (WHO) pre-qualification status for its rifapetine API. The goal is to conduct demonstration runs in the pilot plant by June 2025 and validate the WHO pre-qualification application in September 2025.

If achieved, WHO pre-qualification of CPT Pharma’s rifapetine API would show that the company’s APIs meet high-quality standards. It would also allow CPT Pharma to supply rifapentine API to companies producing medicines for the broader African market, for which a significant proportion of medicines are procured by donors requiring WHO PQ approval.

Note: The Gates Foundation is mentioned in this article. Spotlight receives funding from the Gates Foundation. Spotlight is editorially independent – an independence that the editors guard jealously.  Spotlight is a member of the South African Press Council.

Republished from Spotlight under a Creative Commons licence.

Read the original article.

Categories : Respiratory DiseasesTags :

First New Treatment for Asthma Attacks in 50 Years

On By ModernMedia
Photo by Louis Reed on Unsplash

An injection given during some asthma and COPD attacks was shown to be more effective than the current treatment of steroid tablets, reducing the need for further treatment by 30%. The findings, published in The Lancet Respiratory Medicine, could be “game-changing” for millions of people with asthma and COPD around the world, scientists say.

The type of symptom flare-up the injection treats are called ‘eosinophilic exacerbations’ and involve symptoms such as wheezing, coughing and chest tightness due to inflammation resulting from high amounts of eosinophils, a type of white blood cell. Eosinophilic exacerbations make up to 30% of COPD flare-ups and almost 50% of asthma attacks. They can become more frequent as the disease progresses, leading to irreversible lung damage in some cases.

Treatment at the point of an exacerbation for this type of asthma has barely changed for over fifty years, with steroid drugs being the mainstay of medication. Steroids such as prednisolone can reduce inflammation in the lungs but have severe side-effects such as diabetes and osteoporosis. Furthermore, many patients ‘fail’ treatment and need repeated courses of steroids, re-hospitalisation or die within 90 days.

Results from the phase two clinical trial ABRA study, led by scientists from King’s College London and sponsored by the University of Oxford, show a drug already available can be re-purposed in emergency settings to reduce the need for further treatment and hospitalisations. The multi-centre trial was conducted at Oxford University Hospitals NHS Foundation Trust and Guy’s and St Thomas’ NHS Foundation Trust.

Benralizamab is a monoclonal antibody which targets eosinophils to reduce lung inflammation. It is currently used for the treatment of severe asthma. The ABRA trial has found a single dose can be more effective when injected at the point of exacerbation compared to steroid tablets.

The study investigators randomised people at high risk of an asthma or COPD attack into three groups, one receiving benralizumab injection and dummy tablets, one receiving standard of care (prednisolone 30mg daily for five days) and dummy injection and the third group receiving both benralizumab injection and standard of care. As a double-blind, double-dummy, active-comparator placebo-controlled trial, neither the people in the study, or the study investigators knew which study arm or treatment they were given.

After 28 days, respiratory symptoms of cough, wheeze, breathlessness and sputum were found to be better with benralizumab. After 90 days, there were four times fewer people in the benralizumab group that failed treatment compared to standard of care with prednisolone.

Treatment with the benralizumab injection took longer to fail, meaning fewer episodes to see a doctor or go to hospital. Quality of life also improved for people with asthma and COPD.

This could be a game-changer for people with asthma and COPD. Treatment for asthma and COPD exacerbations have not changed in fifty years despite causing 3.8 million deaths worldwide a year combined.

– Lead investigator of the trial Professor Mona Bafadhel from King’s Centre for Lung Health

She added: “Benralizumab is a safe and effective drug already used to manage severe asthma. We’ve used the drug in a different way – at the point of an exacerbation – to show that it’s more effective than steroid tablets which is the only treatment currently available. The big advance in the ABRA study is the finding that targeted therapy works in asthma and COPD attacks. Instead of giving everyone the same treatment, we found targeting the highest risk patients with very targeted treatment, with the right level of inflammation was much better than guessing what treatment they needed.”

The benralizumab injection was administered by healthcare professionals in the study but can be potentially administered in the GP practice or in the Emergency Department. Benralizumab was safe in the study and similar in safety to many past studies.

Professor Mona Bafadhel said, “We hope these pivotal studies will change how asthma and COPD exacerbations are treated for the future, ultimately improving the health for over a billion people living with asthma and COPD across the world.”

Source: King’s College London