💉 Big Pharma fearless against future pandemics; Sanofi signs on Recludix as partner; US FDA approves anthrax shot
#389 | Chimpanzee gets human drugs; Global antibiotic supply at risk; Migrating mosquitoes
Hi there. Welcome back to The Kable. It’s been a rather eventful week and no, we're not talking about the release of two big films on the same day. This Friday Kable has a recap of the week, and more, to get you caught up on all the life sciences happenings you need to know.
Sandoz is investing about $90 million in one of its sites in Slovenia. The company intends to set up a dedicated Sandoz Biopharma Development Centre here by 2026.
South Korea’s Ministry of Health and Welfare has selected five regions for its Global Bio Campus – a set of facilities designed to train 2,000 members of the biomanufacturing workforce in LMICs annually. This move comes after Korea was designated the Global Training Hub for Biomanufacturing by the WHO in 2022.
Switzerland’s Idorsia has let go of its APAC operations, excluding China; it has sold them to Japan’s Sosei Heptares for almost $466 million.
In the US, a Congressional Committee is taking a peek into the FDA’s foreign drug inspection programme, especially in India and China. Of particular interest to them is why the regulator suspended its unannounced inspection programme conducted in India between 2014 and 2015; they also want to know the details of the Indian facilities which were inspected and served with warning letters in the past decade.
Meanwhile, the US FDA has approved Emergent BioSolutions’ anthrax vaccine for adults between 18 and 65 years of age. The shot is meant for administration, along with antibacterial drugs, in cases of suspected or confirmed exposure to the Bacillus anthracis bacterium. The agency has also approved Daiichi Sankyo’s blood cancer treatment for use in acute myeloid leukaemia patients with a certain gene mutation.
Under its first round of funding allocations, the Pandemic Fund’s Governing Board has approved grants in 37 countries across 6 regions. The selected projects primarily focus on disease surveillance, lab systems and the health workforce. You can find a list of all selected projects here.
And finally, humans are repaying their debt to lab rats. Lab chimpanzees, rather. Scientists from Japan’s Kyoto University have cured a chimpanzee of hepatitis C using a drug developed for humans. Oh, we almost forgot to mention that humans exposed him to the hep C virus for an experiment in the first place.
The Week That Was
What a week it's been. In case you didn't catch all our editions, here's a quick recap for you:
On Monday, we highlighted the inadequacies in Africa's healthcare systems and the region's susceptibility to epidemics. We talked about African Risk Capacity's product which combines risk profiling, outbreak modelling, preparedness training, contingency planning, and risk transfer via a catastrophe bond. This initiative aims to provide timely funding for containment efforts during an outbreak and reduce reliance on often-delayed traditional aid.
Tuesday was busier. Sanofi and AstraZeneca received the US FDA's green light for their RSV preventative therapy, Beyfortus, for babies. Yay.
The Africa CDC partnered with the South African government to launch the Southern Africa Regional Integrated Surveillance and Laboratory Network – RISLNET, for short – in Cape Town. The goal? To address public health concerns by translating data into actionable policies.Â
UN Secretary-General António Guterres warned that a financial crisis is hindering progress towards the 2030 Agenda for Sustainable Development. He noted that the annual SDG funding gap has increased from $2.5 trillion pre-pandemic to $4.2 trillion.Â
Eli Lilly's experimental Alzheimer's drug, Donanemab, showed promising results in a late-stage clinical trial;Â it slowed the cognitive decline of certain groups of Alzheimer's patients by about half a year. But the drug carries risks, including brain swelling and bleeding - three trial participants died due to serious side effects. A US FDA verdict is expected by the end of the year.Â
A report by UNICEF and WHO claimed that global childhood immunisation rates have almost returned to pre-pandemic levels, with 4 million more children fully immunised in 2022 than in 2021. However, the rebound is slower in low-income countries.Â
On Wednesday, we wrote about Pfizer teaming up with Flagship Pioneering in a deal that could end up being worth $7 billion. Together, Pfizer and Flagship are investing $100 million to develop up to 10 new drugs in areas including internal medicine, oncology, infectious diseases and immunology.
In line with the EU-LAC partnership on health launched last year, the EU and PAHO entered a €3.8 million deal to partner on strengthening access to healthcare technology in Latin America and the Caribbean.
The Africa CDC, the WHO, and the Robert Koch Institute launched a Health Security Partnership to Strengthen Disease Surveillance and Epidemic Intelligence in Africa. It will deliver results in the areas of emergency preparedness and response, surveillance and lab capabilities, and ensure a more coordinated and resilient health system.
A neuroinfections researcher wrote about a deadly epidemic of fungal infections in Africa in this piece in The Conversation.
Yesterday, we had some surprising news for you. Just kidding. The WHO raised an alert about tainted cough syrup in Africa. Again. This time it was about Naturcold syrups sold in Cameroon.
And finally, GSK highlighted the recent decline in adult vaccination rates globally. Between 2021 and 2022, approximately 100 million fewer doses than anticipated of certain adult vaccines were administered.
That's all for the week that was. Now back to today.
Newsworthy
Sanofi’s new strategic collab. Sanofi’s newest partner is Recludix Pharma. The $125 million deal – which could be worth over $1.2 billion in biobucks – has a preclinical STAT6 inhibitor at its centre. Targeting the SH2 domain, the first-in-class oral small molecule treatment, is an ambitious one, in that its target has historically been considered undruggable. Recludix is optimistic that it has the answer in its STAT6 inhibitor. Under this new deal, Sanofi will take over clinical development when the candidate reaches phase 2; Sanofi will even commercialise the programme, which is believed to have high potential in treating immunological and inflammatory diseases.
(Recludix Pharma)
Who run the infectious disease market? A new report by GlobalData projects that the infectious disease market will grow at a CAGR of 5.7% through 2029, touching $150 billion in annual sales by then. Pfizer, Gilead Sciences, and GSK will be the major drivers of this growth. Cumulatively, they will account for 62% of all infectious disease drug sales from 2023 to 2029. This growth is even after a fall in Covid vaccines after the 2022 peak, as demand for HIV drugs increases and sales of Covid therapeutics remain high. Strategic price hikes in the US market will help Pfizer maintain its leading position. For Gilead, its HIV drug will be at the core of its growth. For GSK, it will be its shingles vaccine and HIV drug.
(Fierce Pharma)
Intrepid in the face of pandemics. To speed up the discovery and development of new antivirals for future pandemics, seven pharma companies are teaming up, and they’re calling themselves the INTREPID Alliance. AbbVie, Amgen, Gilead, J&J, Novartis, Roche and Takeda are the companies supporting the G7’s 100 Days Mission which aims to have 25 therapies for viral diseases with pandemic potential ready for mid- and late-stage clinical trials by 2026. Later this year, the Alliance will publish a list - based on publicly available info, global landscape assessments and scientific evaluation - of promising antiviral compounds. The therapeutic candidates will be categorized as either clinical agents, pre-clinical agents, or exploratory agents.
(INTREPID Alliance)
Short on antibiotics. Antibiotic resistance is a problem, but so is antibiotic shortage. During the pandemic, an increased demand to treat rising syphilis cases led to a shortfall of essential antibiotics, according to the WHO. The supply of benzathine penicillin G (BPG) - critical for syphilis treatment and rheumatic heart disease prevention and management - is now at risk. The US, Brazil, Australia and some southern African countries have reported shortages. Pfizer has announced a shortage of Bicillin, its version of the injectable, which is one of the world’s oldest antibiotics. Pfizer doesn’t expect the drug’s fragile supply to recover for another year. But if the company decides to stockpile the API to make the drug for its main customers in wealthy countries, low-income countries could be affected by the resulting chain reaction.
Supply issues range from outdated forecasts to limited manufacturers; over 95% of the APIs required to make BPG injections are manufactured by three Chinese companies, with the only other manufacturer being a company in Austria. The BPG shot is also not very profitable due to the low price that governments are willing to pay for the drug, which is expensive to make. These problems aren’t entirely new; a similar issue in the previous decade unveiled the fundamental problems in the supply chain, though evidently, they weren’t addressed effectively.
(Devex)
Getting to the source. Yesterday, we wrote about the WHO’s alert regarding cough syrup NaturCold, linked to at least 6 children's deaths in Cameroon. Fraken International (England), the company listed as the syrup manufacturer, does not even exist, according to the UK regulator. Naturally then, tracking down the source of these killer syrups isn’t going to be easy. Earlier reports of the incidents in Cameroon had mentioned India’s Riemann Labs – photos of a NaturCold box had on them the manufacturing license number (though not the name) of the Indian manufacturer. Now, the WHO has reached out to Indian authorities for their assistance in getting to the origins of the DEG-contaminated syrups.
(Reuters)
R&D
Killing bacteria with peptides. Scientists at the Indian Institute of Science (IISc) have developed a peptide capable of incapacitating a critical enzyme in harmful bacteria, including some of the most deadly, antibiotic-resistant types. The peptide mimics a natural toxin that inhibits topoisomerases, a class of enzymes important to bacterial DNA replication and protein synthesis. The peptide binds to this enzyme-DNA complex, triggering a sequence of events that culminate in cell death, similar to the action of the natural toxin CcdB. This new peptide was tested on various bacteria, both in cell culture and animal models, demonstrating either blocking or "poisoning" a specific topoisomerase called DNA gyrase and disturbing most strains' membranes. Notably, the peptide significantly reduced infections in animal models, showing better performance than the commonly used antibiotic, ciprofloxacin. These findings could guide the development of drugs to be used in combination with existing antibiotics and underscore the potential of targeting topoisomerases in the quest for new antibiotics.
(EMBO Reports)
Killing viruses with compounds. In their second entry into The Kable today, a team of researchers at the Indian Institute of Science in Bengaluru have discovered that picolinic acid, a naturally occurring compound in mammalian cells, can block disease-causing viruses like SARS-CoV-2 and influenza A by preventing their entry into host cells. Though picolinic acid is known to aid in the absorption of zinc and other trace elements and is quickly excreted from the body, recent findings suggest it may have antiviral properties. The team is now working on improving its efficacy, stability, and absorption, and is seeking partnerships with pharmaceutical companies for its clinical development into a broad-spectrum antiviral therapeutic to combat current and potential future viral outbreaks.
(Cell Reports Medicine)
New target for Parkinson’s. Researchers at Northwestern Medicine have discovered that mutations in the parkin gene, a common cause of early-onset Parkinson's disease, disrupt the interaction between mitochondria and lysosomes, two essential cellular organelles. Mitochondria are responsible for energy production in cells, while lysosomes help clear cellular debris. Neurons, particularly reliant on mitochondria for energy, generate substantial cellular waste that lysosomes need to manage. The study found that lysosomes supply vital amino acids to support mitochondrial function, but certain Parkinson's disease mutations prevent these organelles from interacting, leading to dysfunctional mitochondria and subsequent degeneration of vulnerable neurons. This novel insight highlights the importance of organelle communication in the pathogenesis of neurodegenerative disorders and offers a new therapeutic target for Parkinson's disease, namely restoring the mitochondria-lysosome contacts.
(Science Advances)
A frame of reference for the skeleton. Researchers at The University of Texas at Austin and New York Genome Center have used AI to analyse full-body X-ray images and genomic data from over 30,000 participants. This study has shed light on the genetic basis of human skeletal proportions, from the width of the shoulders to leg length. This work not only gives insights into human evolution and the role of skeletal form in musculoskeletal disease but also indicates how these factors could be used to predict the risk of developing conditions like arthritis or back pain. The researchers identified 145 independent genetic loci associated with skeletal proportions, discovered genetic independence between limb and body width proportions, and found connections between certain skeletal proportions and musculoskeletal diseases. The research findings offer a roadmap to the genetic determinants of body structure, providing a fresh understanding of the constraints on skeletal evolution and the origins of certain diseases.
(Science)
And an atlas for the kidney. Bioengineers from the University of California San Diego and other institutions have created the largest single-cell atlas of the human kidney to date, mapping both healthy and diseased cell states from over 90 patients. This effort aims to understand the progression of kidney disease post-acute kidney injury. The study, which analysed over 400,000 cells from healthy, injured, and diseased kidneys, identified 51 different cell types and found that 28 are altered in acute kidney injury. Certain altered cell types remain in a "repair state", continually recruiting immune cells and fibroblasts, leading to inflammation and fibrosis, which in turn drives disease progression. This work reveals new areas within kidney nephrons housing these altered cells, thus broadening our understanding of disease progression pathways. The researchers aim to continue enriching this kidney atlas with data from a more diverse patient population.
(Nature)
Roses are red; violets are blue; we are schizophrenic, so are you. A study published in Cell Genomics reveals that non-inherited mutations occurring during early development might contribute to some cases of schizophrenia. The team analysed the genomes of blood samples from 12,834 schizophrenia patients and 11,648 control individuals and discovered nonhereditary mutations significantly more common in the patients. Notably, they found recurrent mutations in the neurexin 1 (NRXN1) gene, previously linked with schizophrenia, and the ATP-binding cassette subfamily B member 11 (ABCB11) gene, which is involved in liver function but not previously connected to the disorder. While these mutations may only explain a small number of schizophrenia cases, understanding these rare, high-impact mutations may offer insights into disease mechanisms.
(Cell Genomics)
Resisting Covid with heat. A team of researchers from The University of Tokyo has discovered a connection between high body temperature and increased resistance to viral infections. Their study shows that high-heat-exposed mice had elevated basal body temperatures, enabling them to produce more bile acids in a gut microbiota-dependent manner, thereby enhancing their resistance to influenza and SARS-CoV-2 infections. These findings indicate that increased body temperature can stimulate key gut microbial reactions that lead to the production of secondary bile acids, which modulate immune responses and protect the host against viral infections. Furthermore, the researchers identified a decrease in certain bile acids in the plasma of moderate Covid patients, providing potential insights into the variability in clinical disease manifestation and mitigation strategies.
(Nature Communications)
Bottom line
Too cool for mosquitoes? Climate change and weather extremes are causing mosquitoes to migrate to locations that were once too cool for them, including higher altitudes in Africa, posing new challenges in predicting and combating mosquito-borne diseases. The resurgence of locally-acquired malaria in the US, the impact of invasive mosquito species in Djibouti and Ethiopia, and the spread of avian malaria in Hawaii due to migrating mosquitoes underline the novel risks these shifts present. Despite a 27% decrease in global malaria deaths over the past decades, achieved partially through interventions like insecticide-treated nets and the distribution of malaria vaccines, researchers warn that we need to address the growing threats posed by new mosquito species, population shifts, and insufficient funding for mosquito-borne diseases to sustain progress in a warming world.
(Grist)
Must be funny, in a rich man’s world. Money: the cause of all trouble. Climate change is sending us a massive bill, and it’s no surprise that countries are fighting over who will foot it. Climate talks between the US and China are ongoing; ahead of the COP28 climate summit later this year, climate finance is a point of contention. The biggest contributor to climate finance, the EU, wants more countries to contribute. European diplomats argue that China, Brazil, Saudi Arabia and other such countries can’t be put in the same category as the least developed countries and small island developing states.
But the wealthy countries that are obliged to provide $$$ for poorer nations to mitigate and adapt to climate change haven’t yet held up their end of the deal. As countries continue to point fingers at each other without actually doing anything, the nations most vulnerable to climate change are looking for different ways to get the money they need.
(Reuters)
Oh, and Gopal Nair doesn't want you to see this.