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💉 Merck grabs a share of Daiichi's ADCs; WHO's new anti-AMR intervention package; More royalties for Royalty Pharma
#454 | Meds over marriage; circRNA over cancer; Dengue over dealing with climate change
Hello, and welcome back to the final Kable of the week. As essential supplies run out in Gaza, the UN Sec-Gen has called on Israel for “immediate unrestricted access to humanitarian aid” to meet the most basic needs, like food, water, medicine and fuel, of the people of Gaza. The WHO has said that trucks of medical supplies at the border between Gaza and Egypt are “loaded and ready to go” as soon as the Rafah crossing opens, which they hope will be today.
Driven largely by climate change, urbanisation and the increased movement of people, dengue rates have increased 8-fold since 2000. In Burkina Faso, the Health Ministry has declared a dengue fever epidemic as 214 people have died among 50,478 suspected cases in the deadliest outbreak in Africa in years. Roughly 20% of the cases and deaths were reported last week alone.
In Bangladesh, the latest numbers concerning the dengue outbreak reveal 2,350 cases and 8 deaths in a single day. A recent report by the Grantham Research Institute has highlighted a 46% increase in extreme weather events in the country, with high rainfall and temperature leading to the surge in dengue cases in recent years.
In Mexico, too, dengue cases are soaring. Till October 7, there have been 30,320 cases and 48 deaths this year. Confirmed cases this year have risen 337% compared to 2022. 71% of all infections have been detected in just five states.
Pakistani pharma firm PharmEvo – the first company globally to receive WHO prequalification to produce zinc tablets and syrup – is ready to export the product. Zinc supplementation has been shown to reduce the duration and severity of diarrhoea, a disease which claims the lives of around 110 children daily in Pakistan.
The diphtheria outbreak in Guinea has recorded a total of 538 suspected and confirmed cases and 58 deaths from July 4 to October 13 this year. Considering the chronically low vaccination coverage in the country, the WHO assesses that the risk of diphtheria here remains high.
Mozambique is the latest to report an outbreak of H7 bird flu on a farm of over 50,000 laying hens kept in a high biosecurity facility. The country is giving neighbouring South Africa company.
Meanwhile, GE HealthCare and Novo Nordisk are collaborating to advance the clinical and product development of peripheral-focused ultrasound, a non-invasive technology designed to support the treatment of chronic diseases like type 2 diabetes and obesity.
In a “challenging market environment”, the base editing biotech Beam Therapeutics is prioritising meds for sickle cell and certain other diseases. This means that it is narrowing or cutting other research, looking for partners on some of its development programmes, and laying off 100 employees. Beam is hardly the first gene therapy or gene editing company to lay off staff this year.
Building on a 2020 deal, PTC Therapeutics is selling a large chunk of its spinal muscular atrophy drug royalty stream to Royalty Pharma for $1 billion. Both companies retain options for a sale which would transfer more of the rights to Royalty. PTC will use the $$$ it gains to clear its outstanding debt with Blackstone Life Sciences and keep some funds for future operations.
In South Korea, Samsung’s biologics plant has received a Form 483 from the US FDA, outlining data integrity concerns uncovered during a 10-day inspection in August and September.
Amidst exploding demand for GLP-1s, Eli Lilly has hired Swiss contract drugmaker CordenPharma to produce Tirzepatide, the active ingredient in its diabetes drug Mounjaro.
And finally, after all that hype about what AI can do for pharma, Endpoints reports on how the first AI-designed drugs have fallen short in the clinic.
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The Week That Was
Here's a quick look back at what happened in previous editions of The Kable this week.
On Monday, Japan’s GHIT Fund inked an MoU with Senegal’s Institut Pasteur de Dakar to develop diagnostics, treatments, and vaccines for neglected diseases in LMICs. Through tech transfer and sharing know-how with Japanese pharma and academia, the partners will also support low-cost vaccine and diagnostic manufacturing in LMICs.
In a court filing in Indonesia, prosecutors claimed that the cough syrups which killed 200 children last year used ingredients with toxin concentrations of up to 99%. The accused Indonesian drugmaker, Afi Farma, used these ingredients in 70 batches of medicine.
Scientists are looking for new tools to circumvent the issues that come with antibiotics. Their experimental toolbox currently boasts bacteria-killing viruses, microbe-slaying designer molecules, and CRISPR. This Scientific American article explains how these techniques might be the future of treatments for bacterial infections.
The Government of India sought for the traditional medicine system of Ayurveda and related systems to be included in the 11th revision of the WHO’s International Classification of Diseases, or ICD. Officials from the Ministry of Ayush in India said that including Ayurveda in the ICD will provide the means for conducting research and establishing its efficacy. It will also help respond to demands for better regulation of the system and its integration into mainstream healthcare.
On Tuesday, there was news from Africa. In May 2023, the African Union Commission (AUC), the Africa CDC, and Gavi, the Vaccine Alliance had inked an MoU, committing to increase access and accelerate the uptake of life-saving vaccines across Africa. Last week, the partners concluded a three-day forum to outline a pathway for collaborating in alignment with the MoU. Technical experts and senior leaders from the organisations discussed fostering sustainable and equitable systems for immunisations, including reaching zero-dose children and building a resilient workforce. Delegates at the forum also had preliminary discussions on what Gavi 6.0 i.e. Gavi’s next five-year strategic period (2026 to 2030) might look like.
Wednesday was a disappointing day for global agreements. A draft of the proposed Pandemic Accord revealed some promising provisions concerning time-bound waivers of intellectual property (IP) rights and encouragement for patent holders to “waive or manage” royalty payments from developing country manufacturers, even requiring patent holders that have received significant public financing to waive royalties. But these proposals have significant opposition, so we don’t know if all these provisions will stay. Further, some warn that the language of equity provisions is inadequate and “unnecessarily vague”.
As for the latest draft of the “health and climate ministerial declaration” set to be unveiled at the forthcoming UN Climate Conference (COP28) in Dubai - the draft, which emphasises the adaptation of health systems to climate change, omits any direct mention of fossil fuels, a major contributor to climate change. We guess this is what happens when a climate conference is led by someone who is also chief of a fossil fuel company.
Yesterday, we told you about researchers who have been mapping the bird flu virus' evolution for the past 18 years and have noted that the current H5N1 strain, which began wreaking havoc in Europe in 2020, has grown increasingly infectious to wild birds. In 2020, this flu spread among wild birds at a rate thrice as fast as in farmed poultry, courtesy of some pesky mutations that let the virus adapt to various bird species. Researchers say what was predominantly a poultry issue has now become a more extensive animal health concern.
And finally, a new report said that we shouldn't just be worried about wild animals when it comes to diseases hopping over to humans. Even our pets, strays, and those pesky urban animals could be a concern.
Newsworthy
mRNA magic. mRNA fell into the spotlight with Covid vaccines. While mRNA vaccines shifted the course of the pandemic, the underlying science has also opened up possibilities for several other therapeutics. mRNA tech offers the potential of a universal flu vaccine, rather than the existing seasonal ones, which may already become out-of-date by the time they’re manufactured and distributed. mRNA-based cancer immunotherapies, already at the trial stage, can help patients’ bodies produce cytotoxic T-cells and mount a strong anti-tumour immune response; this could greatly enhance existing CAR-T therapies. Finally, mRNA tech could also revolutionise our approach to genetic diseases like hereditary angioedema and ATTR amyloidosis. Most of these solutions are still in their early days. Challenges exist, but research to improve the efficiency of mRNA interventions looks promising. The Dean of the Faculty of Medical and Health Sciences at the University of Auckland writes in The Conversation.
(The Conversation)
(No) vaccines in the time of cholera. Thanks to recent floods, droughts, conflicts, and natural disasters worldwide, many people are dealing with limited access to clean water, poor sewage management, and increasing disease risk. Currently, about 1 billion people are at risk of contracting cholera. By September 10 this year, the WHO recorded 24 countries with active outbreaks, with high case fatality rates. While the disease is preventable and treatable, the world is suffering from a severe shortage of cholera vaccines – not only due to the surge in cases but also because of vaccine manufacturers’ collective lack of interest in producing the cheap vaccine. This article in The Lancet, by members of the Strategic and Technical Advisory Group on Infectious Hazards with Pandemic and Epidemic Potential (STAG-IH), which provides independent advice to the WHO, laments the situation. It laments that the lessons learned from Covid are not being translated to cholera outbreak management. It laments the lack of strong coordinated leadership and the consequent absence of incentives for vaccine manufacturers.
Things may improve in coming years as South Korea’s EuBiologics increases its production capacity, India’s Bharat Biotech develops a new vaccine, and South Africa’s Biovac builds capacity to produce the oral cholera vaccine by 2027. Nonetheless, there is a need for speed, a need for predictable annual vaccine supplies, and a need to develop vaccines that provide longer-lasting immunity and use innovative approaches. Incentive mechanisms, like Operation Warp Speed for Covid, could incentivise more pharma companies from LMCs to invest in vaccine production and development. Beyond vaccines, more efforts are needed for control, early detection and monitoring, data analytics and prediction, remote health systems, GIS mapping, water and sanitation management, and educational interventions. Finally, there is also a need to mobilise tools for treatment. Overall, while the world rushes to find solutions to an as-yet unknown Disease X, we need more funding and political will for an effective multi-sectoral approach to this disease threat that is very much known and among us.
(The Lancet)
WHO v AMR. The WHO yesterday released a core package of 13 interventions to guide countries as they develop, implement, and monitor national action plans on antimicrobial resistance (AMR). Building on the Global Action Plan for AMR, this people-centred approach shifts the narrative to place the needs of people, and the barriers faced by them, at the very centre. It encourages better understanding among policymakers and supports a more practical, programmatic and comprehensive response to AMR at the country level. The document highlights the importance of engaging civil society and community organisations, the private sector, and academia to develop and implement these plans. It calls to integrate AMR response in primary healthcare and health emergency preparedness and response efforts. Overall, the document calls for equitable and affordable access to good quality prevention, diagnosis and treatment services to reduce patient morbidity and mortality and make progress towards the SDGs.
(WHO)
Daiichi makes big bucks. Merck is set to pay Daiichi Sankyo $5.5 billion to develop three of its cancer drug candidates jointly. If the three ADCs reach certain sales milestones in the future, this deal could be worth a whopping $22 billion. The ADCs - Patritumab Deruxtecan, Ifinatamab Deruxtecan and Raludotatug Deruxtecan - are currently in different stages of clinical development to treat multiple solid cancer tumours. The partners will jointly commercialise the drugs worldwide, except in Japan, where Daiichi Sankyo will retain exclusive rights.
(Merck)
R&D
circRNA v cancer. Building on the mRNA story from Newsworthy, this story is about a group of scientists who have used tech based on mRNA to treat cancer. The scientists have designed a circular RNA (circRNA) encapsulated in lipid nanoparticles (LNPs) which reduces adenocarcinoma. Published in Nature Cancer, the research focuses on circRNA which targets cancer cells that express high levels of the eukaryotic translation initiation factor EIF4G2 and the PTBP1 protein. Their results showed controlled cytotoxicity on tumour cells which did not affect neighbouring cells, preventing toxicity caused by mitophagy. Compared to other tumour therapies, this one can rapidly reduce mature tumours' size while inducing specific immunity when certain mutations are present. So this intervention is both therapeutic and preventative. Now the researchers are focusing on developing better LNPs for improved delivery.
(Nature Cancer)
A known cure against a new discovery. In another cancer research update, a study conducted in mice has identified cells which drive the spread of pancreatic cancer and discovered a weakness in these cells which could be targeted using existing drugs. Published in Science Advances, the study found that many patients’ pancreatic cancers contain amoeboid cells, which are aggressive and fast-moving cells that weaken the immune systems. These cells have already been identified in other cancers like melanoma, breast, liver, and prostate cancer. This is the first time they’ve been identified in pancreatic cancer, where they produce high levels of the molecule called CD73. Blocking CD73 reduced the spread of the cancer to the liver and reduced immune support to the tumour. In the long-term, anti-CD73 treatment reduced the incidence of cancerous tumours that spread to the liver from over 66% to about 36%. Further research is needed to translate these findings to humans, but things look promising, especially since we already have anti-CD73 drugs which are being tested in clinical trials for cancer.
(Science Advances)
The Kibble
More meds than matrimony. New research from the US reveals that Americans born in 2019 are likely to spend a more significant portion of their lives on prescription drugs than being married or in education. Drawing data from extensive surveys by the AHRQ and CDC from 1996-2019, researchers found that American males will be on prescription medications for roughly 48% of their lives, while for females, this figure rises to 60%. These alarming medication usage rates, especially among women, are attributed not just to contraceptives but also to other hormone-related drugs, psychotherapeutic medications, and painkillers. In contrast, men often consume cardiovascular drugs. Concerningly, there's a noted disparity in drug use among racial and ethnic groups, particularly with statin use being lower among non-Hispanic Black men. The study also highlighted the growing trend of polypharmacy, with many now taking five or more drugs simultaneously. These findings raise questions about the long-term effects of these medications, potential health risks, and the escalating healthcare costs associated with prescription drugs. And while this particular study pertained only to the US, how much are you willing to bet results will differ in other parts of the world?
(Demography)
Bottom line
Prenatal chemical exposure and childhood obesity. A study reveals that children exposed in utero to higher levels of pesticides, fungicides, and other synthetic chemicals are likelier to experience increased body mass index (BMI) during childhood. These chemicals, termed "obesogens," can interfere with metabolism and hormones, possibly contributing to obesity. The research, conducted by the Barcelona Institute for Global Health in Spain, involved analysing 23 contaminants in 1,911 expectant mothers. Findings reinforced the significance of synthetic chemicals on weight gain and showed a correlation between prenatal exposure to "persistent" chemicals and increased BMI risks in children. Such chemicals, including hexachlorobenzene (HCB) and dichlorodiphenyldichloroethylene (DDE), linger in the environment and the human body for extended periods. The study accentuates the need for more research on prenatal environmental chemical exposure and its long-term effects.
(Environmental Health Perspectives)
Oh, and Gopal Nair doesn't want you to see this.
Every Friday, we relax our paywall so you can see for yourself the value of paying ₹500/month (or ₹4500/year) for a concise download of the day’s top news and events at the intersection of human and animal health, climate change and environmental science. Please consider becoming a paid subscriber.