#489 | RA drugs for diabetes; Oily fish for your heart; Climate financing for public health

Hello, and welcome back to The Kable for one last time this week. 

Pandemic accord negotiations are still on-going at the WHO but, as with most things at this particular multilateral agency, not everything is hunky dory. Reports suggest the establishment of a single oversight and compliance body for both the new pandemic agreement and amended International Health Regulations (IHR). This proposal, responding to civil society calls for independent oversight and addressing trust issues between countries and citizens, aims for coordinated and effective monitoring of global health emergencies, with discussions on financing and operational synergies between the WGIHR and INB also underway. Still underway, we might add.

South Africa\’s National Health Insurance Bill, aiming to reform the health system through a national insurance plan, was passed by the National Council of Provinces despite opposition from various groups. This bill seeks to provide universal health coverage and establish a fund for treatment, but faces criticism for unclear funding details and potential constitutional rights infringement, setting the stage for legal challenges. Health bodies have also warned that passage of this bill could see a mass exodus of doctors to foreign shores.

In Kenya, authorities have launched a national rural sanitation and hygiene protocol, supported by UNICEF, to improve sanitation and public health through a phased approach for clean latrines and waste disposal, and investment in hygiene solutions in rural schools, homes, and healthcare facilities.

Zambia, meanwhile, is experiencing elevated anthrax activity across multiple provinces with 775 cases reported since October, prompting health officials to launch public education campaigns on anthrax prevention and control, and advising the public to purchase meat only from authorised sources.

The WHO and the Irish Government have signed an agreement to pilot a project worth €200,000 in Tanzania, aimed at strengthening health system resilience and emergency response, particularly at the sub-national level, in response to challenges like diseases, climate change, and natural disasters.

In the first acknowledgment that things might be far from ideal in the Democratic Republic of Congo, the US CDC has issued a health alert about a more infectious and severe subtype of the mpox virus, Clade I, spreading in the DRC, noting its new evidence of sexual transmission and, of course, the absence of cases in the US so far.

CEPI’s Centralised Laboratory Network is one of its biggest hopes at achieving its 100-day mission. That hope got bolstered further with the addition of Charles River Laboratories to the network.

In corporate news, Vanda Pharmaceuticals has acquired US and Canadian rights to J&J’s multiple sclerosis medication Ponvory for $100 million, marking a significant expansion of its commercial portfolio with a drug that has potential in treating various autoimmune disorders.

In a not-surprising burst of pre-Christmas activity, the US FDA has announced a whole host of voluntary drug recalls, including VistaPharm\’s recall of aminocaproic acid for high ethylene glycol content, Aptotex\’s recall of paroxetine hydrochloride tablets due to impurity issues, Glenmark Pharmaceuticals\’ recall of Indomethacin and Naproxen for mislabeling, and Teva\’s recall of testosterone gel for viscosity issues.

And finally, CHAI and Reproductive Health Supplies Coalition have released the ninth edition of the Family Planning Market Report, offering detailed insights into contraceptive procurement and market trends in low- and lower-middle income countries, including new data on domestic government financing. 

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The Week That Was

We kicked the week off by dispelling concerns about a potential new infectious disease. The recent surge in respiratory illnesses in China has been caused by known pathogens, according to a health official. There is no sign of new infectious diseases, and experts within and outside China have not expressed alarm. 

What didn\’t entirely dispel concerns, however, were updates from COP28. In a historic event, 124 countries endorsed the Declaration on Climate and Health. This marks the first time that the health impacts of climate change have received the attention they deserve in UN climate talks, even though they\’re not legally binding. Notably, however, the health declaration makes no mention of fossil fuels. Disappointing, but not surprising, as the COP28 President (also CEO of the UAE national oil company Adnoc) is claimed to have said that there is “no science” behind claims that fossil fuel phaseouts will slow global warming. Further, two of the world’s top three greenhouse gas emitters – the USA and India – have not yet endorsed the declaration.

Nonetheless, not all is doom and gloom on the climate and health front. The Green Climate Fund (GCF), the United Nations Development Programme (UNDP), and the WHO launched an initiative to increase support for developing countries to mitigate and respond to the impacts of climate change on health. Focused on 14 countries in Africa, Asia, and Southeastern Europe, the initiative will address gaps in financing and the fragmentation of efforts against climate and health. The World Bank has also announced a new Climate and Health Program to urgently respond to the health impacts of climate change in LMICs.

On Tuesday, we took a journey – with Devex and the Head of the African Medicines Regulatory Harmonisation (AMRH) programme – through progress in establishing the African Medicines Agency (AMA). In 2021, the AMA treaty came into force, but still, the journey to the launch of the Agency is long and winding. AMA work is already ongoing in technical committees. Existing committees include the African vaccines regulatory forum (for clinical trial oversight and complex product reviews) as well as committees for medicines quality control and market surveillance, blood product regulation, medical devices, regulatory capacity development, medicines policy and regulatory reforms, and information management systems. There are also three new committees for the evaluation of medicinal products, good manufacturing practices, and pharmacovigilance and safety surveillance – the last of these is set to begin work in January 2024. Overall, the AMA is taking its time to get things up and running, but with an ambitious cross-jurisdictional structure responsible for policies and practices across a large continent and a full range of healthcare commodities, that may not be such a bad thing. Progress so far is promising.

On Wednesday, we told you about Gavi\’s expansion of its portfolio and its introduction of new vaccine programmes. Countries eligible for Gavi support can now apply to introduce DTP (diphtheria, tetanus and pertussis) boosters and switch to a hexavalent vaccine, which provides combined protection against DTP, hepatitis B, Haemophilus influenzae type b, and polio. The programmes will be particularly helpful to countries in Asia and sub-Saharan Africa, which bear the greatest burden of mortality from DTP. In addition to these interventions, Gavi is in the process of developing its 2024 Vaccine Investment Strategy, with hopes of including the hepatitis B birth dose and rabies vaccines in its portfolio of offerings.

There were also encouraging updates concerning the future of public health in Africa and the Eastern Mediterranean. Under a five-year strategic plan developed jointly by the Africa CDC, the WHO, the Bill & Melinda Gates Foundation, the UK Health Security Agency, and partners, over 90% of countries in the Africa and Eastern Mediterranean regions should be able to coordinate their national outbreak responses within the next half-decade. Through the development of Public Health Emergency Operations Centres (PHEOCs), this will include strengthening the capabilities of routine and surge public health teams by 2027. By the end of 2027, the plan aims to have 8 PHEOCs designated as centres of excellence.

And finally, yesterday, we covered the failure of PrEPVacc, a trial billed the “last roll of the dice” for a near-term HIV vaccine. PrEPVacc was testing two different vaccine regimens on volunteers in Uganda, Tanzania, and South Africa since 2018. It was pioneering in that it was one of the first large, African-led HIV vaccine trials and one of the first to incorporate PrEP (pre-exposure prophylaxis) daily antiviral pills. However, an independent data monitoring committee concluded that there was almost no chance that the study would show efficacy, leading the investigators to halt the trial early. While no new volunteers will be dosed, researchers will continue to follow participants into next year to eventually decode what went wrong with their intervention. A portion of the study which compares two forms of oral PrEP will also continue. HIV vaccine researchers, though disappointed, are not surprised.

Newsworthy

Coughing up the costs of contamination. The WHO has issued a medical product alert for five different syrup and suspension medicines. These include Alergo Syrup, Emidone Suspension, Mucorid Syrup, Ulcofin Suspension, and Zincell Syrup. Contamination of these products was first detected in the Maldives and Pakistan, and subsequently, the affected products have also been detected in Belize, Fiji, and the Lao People’s Democratic Republic. A total of 23 batches of these products are affected. For a change, the manufacturer of all the affected products, Pharmix Laboratories, is not from the usual suspect but from Pakistan. The contaminants found, however, are the usual suspects of diethylene glycol (DEG) and ethylene glycol (EG).

An inspection of Pharmix’s manufacturing facility and records by the Drug Regulatory Authority of Pakistan (DRAP) has suggested that DEG and EG may be present in other products and batches produced by Pharmix, the safety and quality of which cannot be guaranteed. DRAP has instructed Pharmix to stop production of all oral liquid dosage medicines and has also issued a recall alert for the five syrup medicines. Thankfully, no adverse effects linked to these products have been notified to date. Nonetheless, the WHO recommends increased vigilance and testing concerning oral liquid dosage medicines produced by Pharmix between December 2021 and December 2022.
(WHO)

Approval for the AVMA. After 18 months of collaboration with the African Union and the Africa CDC, Gavi, the Vaccine Alliance, has announced its Board’s approval to establish the African Vaccine Manufacturing Accelerator (AVMA). Due to launch in June 2024 at an event hosted by the Africa CDC and France, the unique financing mechanism will aim to build a sustainable African vaccine manufacturing industry capable of improving the region’s resilience to disease outbreaks and other health emergencies. The scheme will make up to $1 billion available to help African vaccine manufacturers offset high start-up costs and secure demand assurance.

The AVMA is the final pillar of Gavi’s regional manufacturing strategy. It will focus on priority antigens, product profiles, and vaccine platforms; it will also construct incentives for fill-and-finish and drug substance production to establish a thriving end-to-end African vaccine manufacturing network. How will it work? The Accelerator will pay manufacturers a sum of money when the WHO approves their vaccines; it will also provide an additional allocation if they win bids to supply vaccines to low-income countries via the Gavi co-financing mechanism.

Additionally, learning from the Covid situation, the Gavi Board has approved a $500 million investment in a First Response Fund – part of a wider Day Zero Financing Facility – which will ensure financing is immediately available from the start of a future pandemic. $22 million will be dedicated to pandemic prevention, preparedness, and response activities by countries, civil society, and other partners. Finally, the Board has also approved an initial amount of $290 million to fully fund catch-up doses for children who missed routine vaccinations. Funding for all these activities will come from the money leftover in the COVAX initiative, which was set up during the pandemic to get vaccines to the world’s poorest countries.

At the same meeting where these initiatives were announced, the Board approved the inclusion of the new multivalent meningococcal conjugate vaccine (MMCV) into the Gavi portfolio and confirmed the proposed shortlist for Gavi’s 2024 Vaccine Investment Strategy, including vaccines for tuberculosis, group B strep, shigella, dengue, potentially continued support for Covid, and a stockpile of hep E vaccines.
(Gavi) 

R&D

Protein hide-and-seek. In a scientific breakthrough, researchers have finally pinpointed the elusive protein behind a unique form of early-onset dementia, frontotemporal dementia (FTD). This discovery is a big deal because it sheds light on FTD, the second-most common dementia, which strikes people relatively young, in their 40s or 50s. FTD is known for altering behaviour, personality, language, and movement due to the degeneration of specific brain regions. Previously, the exact protein causing certain rarer FTD cases remained a mystery, leaving researchers without clear targets for treatment. However, in this new study, researchers used advanced cryo-electron microscopy to analyse brain tissue from FTD patients, expecting to find the FUS protein, previously linked to FTD and ALS. But instead, they identified TAF15, a protein previously not associated with neurodegenerative diseases. This finding opens up a whole new avenue for understanding and potentially treating this specific subtype of FTD, similar to how discoveries about proteins like amyloid-beta and tau transformed Alzheimer\’s research. But, like with Alzheimer\’s and Parkinson\’s, this is just the starting point, and there\’s a long road ahead filled with potential challenges and discoveries.
(Nature)

Old drug, new gig. In a recently published study, researchers at St Vincent’s Institute of Medical Research in Melbourne have demonstrated that a drug commonly used for rheumatoid arthritis, baricitinib, can effectively slow down the progression of type 1 diabetes. This world-first human trial found that baricitinib can preserve insulin production in newly diagnosed patients, if treatment begins within 100 days of diagnosis. This research is particularly exciting as it offers the first tablet-based, disease-modifying treatment for type 1 diabetes, a condition that has historically been managed with insulin injections or pumps. The trial revealed that participants taking baricitinib required significantly less insulin, marking a potential paradigm shift in managing this lifelong autoimmune disease. This advancement could significantly alleviate the burden of constant glucose monitoring and insulin administration for those with type 1 diabetes and their families, while reducing the risk of long-term complications associated with the disease. The researchers are optimistic about the clinical availability of this treatment, viewing it as a fundamental improvement in type 1 diabetes control.
(NEJM)

The Kibble

Fishing for heart health. In a fishy twist on family health, it turns out that if your relatives have a history of cardiovascular disease, you might want to start befriending salmon, mackerel, and their oily friends. Researchers at Karolinska Institutet, using data from over 40,000 people, discovered that those with a family tree lacking in omega-3 fatty acids face a 40% higher risk of heart issues. The study, not content with just surveying people\’s dinner plates, actually measured the levels of EPA/DHA in participants, making it less about what they said they ate and more about what their bodies screamed, which was \”We need more fish!\” So, if your family history is a bit heart-wrenching, it might be time to consider turning your diet into a seafood saga, as these researchers believe that the way to a healthy heart is, quite literally, through the stomach!
(Circulation)

Bottom line

Funding climate-linked health needs. Over the next three years, the Global Fund to Fight AIDS, Tuberculosis and Malaria will spend 70% of its funding in 50 of the most climate-vulnerable countries around the world. There is a notable change in this three-year cycle when it comes to what countries indicate they want to spend their funding allocations on: about 40% of funding requests explicitly mention climate change-related needs. Overall, the Fund’s priorities in this cycle are malaria (which is highly climate-sensitive), disease surveillance, and supply chain improvements. The WHO estimates the direct damage costs of climate change to health at $2 billion to $4 billion annually by 2030. But as less than 2% of multilateral climate finance is invested in health projects, these changing allocations from countries could not have come at a better time.
(Devex)

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.