💉 AbbVie acquires an ovarian cancer ADC; WHO releases its World Malaria Report; FIND, Rwanda Biomedical Centre accelerate diagnostic innovation

#484 | White lung syndrome’s world tour; A lesson from antibiotics' ancestors; A record-breaking 2023

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Dec 01, 2023

Hello, and welcome back to our Friday Kable – free, so that you can catch up on the eventful week that was.

COP28 kicked off in Dubai yesterday. The first day of the fortnight-long climate conference saw a major breakthrough, with delegates agreeing on the operationalisation of a loss and damage fund: a long-standing demand of developing countries facing the worst effects of climate change. The UAE has said that it will commit $100 million to the fund. Germany is reported to have pledged another $100 million. The EU, the UK, the US and Japan have also announced contributions. With no defined replenishment cycle, there are questions about the long-term sustainability of the fund; but for the fact that things are finally moving, we celebrate.

Also at COP28, the UAE is reportedly preparing to announce a new $30 billion climate-focused investment fund. This fund will have backing from some of the world’s biggest investors, like BlackRock. While the UAE will provide a large part of the funds needed, private equity firm TPG and infrastructure investor Brookfield will also be involved.

Thanks to the Covid pandemic, the number of zero-dose children in Africa rose by 24% in 2022 compared to 2019. 20% of children on the continent are still missing basic, life-saving vaccines. Now, the WHO and partners are calling for accelerated action to put Africa back on track to achieve the Immunisation Agenda 2030 goals.

Ethiopia has become the latest country to ratify the treaty for the establishment of the African Medicines Agency (AMA)!

Unfortunately, this progress on the AMA front is balanced by a cholera outbreak in Ethiopia’s Somali region. The disease is making things worse for thousands displaced by floods. Of 772 confirmed cases, there have been 23 deaths in just two weeks.

Across the continent, the Pharmaceutical Society of Nigeria has released a comprehensive blueprint to strengthen healthcare and achieve universal health coverage (UHC). It includes promoting research and local manufacturing of pharma products. It also covers advocacy, clinical services, specialisation, and political action.

Still in Nigeria, the Pharmaceutical Wholesalers and Distributors Association of Nigeria (PWDAN) recently inked an MoU with the P2P Pharmaceutical Supply Chain Coordination Platform. The goal is to develop a robust, inclusive, and tech-driven drug distribution and traceability system for pharma products.

On the sidelines of CPHIA, FIND and the Rwanda Biomedical Centre inked a collaboration agreement to accelerate diagnostic innovation, strengthen regional manufacturing, and boost disease surveillance capabilities. The agreement is aligned with the resolution on diagnostics adopted by the World Health Assembly earlier this year.

Since 2021, the government of Rwanda has been working with BioNTech on the construction of a state-of-the-art mRNA vaccine manufacturing plant. BioNTainers have been shipped and installed. The 30,000 sq m facility is ready. It will be inaugurated on 18 December.

Uganda’s mystery disease outbreak, which killed at least 17 people, has been confirmed as anthrax.

In the only story from South America today, research from the World Mosquito Program and the University of Antioquia has revealed that dengue cases have dropped to a 20-year low in Colombia’s Aburrá Valley. How, you ask, did they achieve this? By releasing Wolbachia mosquitoes in large numbers – an intervention that has already shown success in Bello, Medellín and Itagüi.

In Japan, the health minister has presented a draft plan to strengthen regulations governing the sale of over-the-counter (OTC) drugs for cough and cold. This move comes in response to the increase in overdoses among young people – only one of the cough and cold medicine horror stories coming out from around the world in recent years.

Since we’re already speaking of Japan, the country’s Otsuka Pharmaceutical’s US subsidiary has acquired the American women’s health food company Bonafide Health for $425 million.

Now for Big Pharma. AbbVie has announced its agreement to acquire Massachusetts-based biotech ImmunoGen for $10.1 billion. With this acquisition, the pharma giant gets its hands on the biotech’s recently approved first-in-class ADC treatment for ovarian cancer, Elahere.

Johnson & Johnson MedTech is shelling out $400 million upfront to acquire the privately-held Laminar, a medical device company focused on eliminating the left atrial appendage in patients with non-valvular atrial fibrillation.

The clinical-stage biopharma Lumen Bioscience has received $5.5 million in new funding from the US Department of Defense. These funds will go towards the development of enabling technologies for needle-free vaccines

A partnership between the University of Cambridge, AstraZeneca, and the UK’s Medical Research Council has resulted in the establishment of a new functional genomics lab at the Milner Therapeutics Institute. Functional genomics deals with genetic changes that affect disease development and progression. The new facility will provide researchers in the UK with a range of biological and technical tools – including an advanced automated arrayed-CRISPR screening platform – to study the relationships between genes and conditions like metabolic, cardiovascular, and respiratory diseases. Operations are expected to start in 2024.

After Intas, which received a warning letter from the US FDA recently, Dr Reddy’s Laboratories is next in line to draw the agency’s ire. The FDA has issued a Form 483 to the generics giant, citing 9 observations made during an inspection of a site in Telangana, India in October. At least Dr Reddy’s has Kilitch Healthcare’s company in its misery.

And both drugmakers have the company of Chinese pharma. The US FDA and federal partners are investigating reports of leaks, breakages, and other quality problems with plastic syringes manufactured in China. If necessary, the FDA will prevent plastic syringes made in China from entering the US.

Turkey’s competition authority has launched an investigation into 19 pharma companies to determine if they have committed violations of competition law. The companies being investigated include AstraZeneca, Bayer, GSK, J&J, Bausch & Lomb, Sanofi, and Pfizer.

Mystery outbreaks seem to be all the rage these days. In the East African nation of Comoros, the health system is overwhelmed by patients with symptoms of the flu, fever and cough, or gastroenteritis. The nature and origin of this outbreak is as yet unknown.

Speaking of mystery illnesses, we have one that is not such a mystery anymore. In rare cases, hunters and fishermen handling seals can contract painful hand infections known as blubber finger. Penicillin treatments are ineffective for these infections which may even require surgical intervention. Now researchers at Denmark’s Statens Serum Institut have discovered that the infection is caused by a unique, previously unknown mycoplasma bacterium which they have named Mycoplasma phocimorsus. They’ve found this bacterium is vulnerable to antibiotics other than penicillins, which means that hunters and fishermen in Denmark can now go seal-hunting stress-free!

And finally, cases of the bacterial infection called mycoplasma pneumoniae or white lung syndrome have seen a recent spike in China. Paediatric patients in Ireland, too, have been diagnosed with this infection, which has also made its way to Denmark and to Ohio in the USA. Here’s what this illness is all about.

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The Week That Was

This week began with the news that for the first time, the WHO has confirmed sexual transmission of mpox in the Democratic Republic of Congo as the country goes through its biggest-ever outbreak. So far, the outbreak has infected over 12,500 people and killed over 580. African scientists believe the confirmation of sexual transmission is a concerning development and could make it tougher to stem the spread of the diseases.

Also on Monday, Reuters reported that drugmakers around the world are now trying to limit their reliance on Chinese contractors who produce drugs used in clinical trials and early-stage manufacturing. And where are all these contracts going, if not to China? To India, of course.

Oh also, large-scale disease outbreaks which primarily kill children are spreading globally. And we have Covid-associated disruptions to blame for this, with over 60 million children currently without a single dose of standard childhood vaccines, mainly in Nigeria, Ethiopia, India, Congo and Pakistan. Additionally, 85 million children are under-immunised because of the pandemic.

On Tuesday, amid a raft of mystery illnesses, the US FDA withdrew from the Global Harmonisation Working Party (GHWP), one of many groups working to align international standards for medical devices.

On Wednesday, the Clinton Health Access Initiative (CHAI) released a continental market-shaping strategy for a sustainable vaccine manufacturing footprint in Africa. Such a footprint would target end-to-end production capacity of about 170 million doses annually across 8 identified antigens and nearly 460 million doses annually of additional antigen-agnostic drug product (DP) capacity.

Also, a new advisory network project called Rapid Optimal COVID-19 Responses Through Science Advice of a Multidisciplinary Multilateral Demonstration Network was spawned to bridge the gap in formal liaison mechanisms between Africa’s many research structures and advisory institutions.

On the same day, the US FDA sounded the alarm over the "serious risk" of CAR-T therapies potentially causing new cancers in patients.

Yesterday was a big day for all things Africa. First came the news that the Africa CDC and the AU Commission are working on developing the Africa Epidemics Fund, a new pool of finance to help countries prepare for and respond to disease threats.

Then, a new African civil society network was unveiled. Christened the Resilience Action Network Africa, or RANA, this network will address pandemics and climate crises. It has been established by more than 30 African organisations which are part of the global Pandemic Action Network (PAN).

And finally, CEPI, the Korea-based International Vaccine Institute (IVI), and the Gambia’s Medical Research Council Unit The Gambia (MRCG) launched the Research Preparedness Program West Africa (RPPWA). They will support a consortium of regional stakeholders to boost the capacity of clinical research sites across West Africa, enabling them to conduct large-scale clinical trials for vaccines to fight regional disease threats.

Newsworthy

Climate change is not alone. The fight against malaria is faltering globally, with the WHO, in its 2023 World malaria report, reporting a concerning rise of about 5 million cases in 2022, pushing the total to an estimated 249 million. This increase surpasses global targets for controlling the disease, indicating a deviation from the WHO's target of reducing malaria case incidence to 26.2 cases per 1,000 at-risk people by 2025. The current trajectory is significantly off track, with the actual incidence being 58.4 cases per 1,000 at-risk individuals. Factors contributing to this setback include pandemic-related disruptions, climate change-induced extreme weather events, rising drug and insecticide resistance, and conflict. While malaria deaths had declined from 864,000 in 2000 to 576,000 in 2019, they increased during the pandemic, with an estimated 608,000 deaths in 2022, primarily among young children. Notably, areas experiencing the most extreme weather saw significant surges in cases, exemplified by a five-fold increase in malaria cases in Pakistan following floods. The only ray of light among all this malarial gloom is the introduction of two new malaria vaccines, but that response too is hampered. By a significant funding gap, with $4.1 billion invested in 2022 against a need of $7.8 billion.
(WHO)

Pharma faux pas. The news from India appears to be stuck in a troubling repeat mode, as the country's drug regulator, the Central Drugs Standard Control Organisation (CDSCO), has uncovered the widespread use of industrial-grade excipients in the production of medicines, a practice unfit for human consumption. This alarming discovery was made following international complaints, leading to an investigation and multiple inspections. The CDSCO found that unlicensed traders supplied industrial-grade materials like gelatin and propylene glycol, imported from various countries including China, to pharmaceutical manufacturers. This contravenes the Drugs and Cosmetics Act, which mandates the exclusive use of pharma-grade excipients in medicine. The Drug Consultative Committee (DCC), advising on the uniform implementation of the Act, has proposed issuing an advisory to state authorities to ensure compliance. The DCC's meeting minutes highlighted that low-cost, industrial-grade gelatin, potentially containing toxic substances like carcinogenic chromium compounds, has been blended with high-quality Indian gelatin in capsule manufacturing. This issue of excipient adulteration, including the use of substances like glycerin and isopropyl alcohol (IPA) as industrial-grade materials in drugs, has been reported multiple times, raising serious concerns about the safety and quality of pharmaceuticals in India.
(The Economic Times)

Pharma is not alone. Contamination issues in India extend to Ayurveda too, as evident from a recent investigation where three people have died after consuming a contaminated Ayurvedic syrup. The incidents occurred in Kheda, Gujarat over the last three days. The syrup, which was found to contain traces of methyl alcohol, is suspected to be the cause of death. Symptoms experienced by the victims included vomiting, disorientation, and chest pain. The syrup, bought from a local shop, was reportedly brought from outside the state, and both the manufacturer's name and address on the bottle were found to be fictitious. Authorities have detained the seller and supplier while the health department is conducting a parallel investigation. This incident follows previous findings by the WHO and other health agencies about contaminated cough and cold syrups made by several Indian companies. Additionally, two more deaths in the same district, showing similar symptoms, are under suspicion of being linked to the same cause, with test results pending. Another individual who consumed the syrup is currently under treatment.
(Reuters)

R&D

Cytokine receptors to the rescue 🦸‍♀️. In paediatric patients of leukaemia, immunotherapy using modified chimeric antigen receptor (CAR) T cells has improved survival rates. But when it comes to treating solid tumours, these therapies aren’t as effective; what’s worse, they can also be quite toxic. In a study published in Nature Biomedical Engineering, researchers from St Jude Children’s Research Hospital have found just the solution – adding a modular chimeric cytokine receptor to CAR T cells boosts their efficiency in multiple solid tumour models. Further, by delivering the pro-immune signalling of cytokines only to the CAR T cells, systemic toxicity is also eliminated. This approach has the potential to improve CAR T-cell therapy for solid tumours and brain tumours.
(Nature Biomedical Engineering)

Learning from our ancestors. Antibiotics are largely “the products of intra and inter-kingdom evolutionary warfare,” say the authors of a study published this week in Nature Communications. To understand the evolutionary mechanisms of antibiotics and learn some lessons from them, they took their magnifying glasses to the origins of a very valuable class of compounds referred to as lipid II targeting glycopeptide antibiotics (GPAs). These are usually used as a last resort to treat antibiotic-resistant bacterial infections. This journey back in time revealed the structure of paleomycin, which is the ancestral parent of lipid II targeting GPAs. The researchers compared the process to bringing woolly mammoths or dinosaurs back to life. By understanding nature’s optimisation strategies, scientists may now have the foundations for future efforts to develop new antibiotics. As the world grapples with a growing burden of antimicrobial resistance, this study couldn’t have come at a better time.
(Nature Communications)

The Kibble

Microorganisms for your mood. Scientists estimate that there are about 39 trillion microorganisms – fungi, viruses, and bacteria – inside each of us. Naturally, deciphering the job descriptions of each of these is quite complicated. But scientists at the University of Virginia School of Medicine have narrowed their focus to Lactobacilli, the bacteria found in yoghurt and other fermented foods. From their prior research in mice, they already knew that this bacteria’s skill set included reversing depression; further, the bacteria went AWOL subsequent to psychological stress. Now, the researchers have uncovered the mechanisms underlying this mood-uplifting effect. Lactobacilli maintain the levels of the immune mediator interferon gamma, which regulates our bodies’ response to stress and helps keep depression at arm’s length. In future, we might see special probiotic supplements designed to help us fight the blues.
(Brain, Behavior, and Immunity)

Bottom line

A record-breaking 2023. What better way to kick off a global climate summit than with a report on the Provisional State of the Global Climate in 2023? The World Meteorological Organisation released the report at the opening of COP28 to throw light on what exactly is at stake in the deliberations that are to come over the next fortnight. 2023 is on track to be the warmest year ever recorded since we started keeping track 174 years ago. Till the end of October, data showed that we were about 1.4°C warmer than the pre-industrial baseline. But why stop at just one record? The year also witnessed record sea surface temperatures and sea level rise, in addition to record low Antarctic sea ice, which was about 1 million square kilometres less than the previous record. Greenhouse gas levels continue to rise, and extreme weather continues to cause death and devastation. Next year could be worse.
(WMO)

Oh, and Gopal Nair doesn't want you to see this.