💉 A potential threat to the world's generics supply; Pfizer, BioNTech's promising combo vaccine; Sanofi's spin-off of its consumer health business
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💉 A potential threat to the world's generics supply; Pfizer, BioNTech's promising combo vaccine; Sanofi's spin-off of its consumer health business
#459 | Malarial protein discoveries; A phage diet for cells; Migraines in your genes
Hello, and welcome to our free Friday edition of The Kable. Today, we kick things off with good news on the respiratory virus vaccine front. Pfizer and BioNTech have announced positive results from phase 1/2 studies of their mRNA-based combo vaccine, which generated robust immune responses to influenza A, influenza B, and SARS-CoV-2 strains. A phase 3 trial for the flu-Covid combo shot is expected in the coming months. Just earlier this month, Moderna had also announced phase 1/2 success for its combo shot.
In the latest Big Pharma legal drama, Novartis is suing Takeda because it believes that a former employee of its Egyptian subsidiary – who subsequently moved to Takeda – had been distributing trade secrets mined from about 10,000 Novartis files. Novartis claims that its attempts to resolve the issue out of court have been stonewalled by Takeda, while the latter says it has been actively investigating the matter. The Swiss pharma is seeking a subpoena to take a look at Takeda’s business records to protect its own business interests and verify if its information is being used improperly.
Joining its peers like J&J, GSK, Pfizer, and Novartis, which spun off their consumer health businesses, Sanofi intends to separate its consumer healthcare business in the last quarter of 2024, at the earliest, by creating a publicly-listed France-headquartered entity.
A unit in Switzerland of the Belgian drugmaker UCB is the latest to receive a Form 483 from the US FDA. It includes observations concerning deficient quality control, record-keeping, and more.
Meanwhile, the Drug Controller General of India has approved MSD’s Keytruda to treat triple-negative breast cancer and renal cell carcinoma in adults. The treatment is now approved for 14 indications across 8 tumour types in the country.
And finally, the UK is witnessing a dramatic increase in diarrhoeal illnesses caused by the intestinal parasite Cryptosporidium. October saw peak cases about thrice as much as is usual for this time of year. The outbreak is still ongoing, but its source is still unclear – so far, authorities suspect international travel and swimming.
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The Week That Was
For all of you who missed our previous editions this week, here is a quick recap -
On Monday, Labiotech traced Africa’s journey so far towards potentially becoming the next big biopharma and vaccine manufacturing destination. From South African Afrigen Biologic’s recent partnership with Danish Evaxion to develop an mRNA vaccine against gonorrhoea to Institut Pasteur de Dakar and Mastercard Foundation’s $45 million partnership; from BioNTech’s work in Rwanda to Shanghai Fosun Pharmaceutical and the IFC's collab for a new pharma hub in Côte d’Ivoire, and lots more, progress so far paints a promising picture for the future of African pharma manufacturing.
To offset an anticipated drop in oncology sales, Switzerland-based Roche decided to shell out $7.1 billion to diversify its portfolio. Roche announced that it will buy Telavant Holdings, in which Roivant and Pfizer have placed the rights to develop, manufacture, and commercialise RVT-3101 - an experimental drug designed to treat inflammatory bowel disease (IBD) - in the US and Japan. This drug could potentially become a best-in-class drug for IBD.
Human challenge trials have been a controversial approach, especially when it comes to the Zika virus, because of the risks to participants and the lack of treatments. But researchers at the Johns Hopkins Bloomberg School of Public Health showed for the first time that they can safely and effectively infect human volunteers with Zika; US regulators and the WHO have ruled their model safe and scientifically important.
Researchers from Duke University Medical Center’s Duke Human Vaccine Institute proved early success in a vaccine that offers protection against a range of coronaviruses like SARS and MERS as well. Their study, published last week in Cell Reports, showed that their pan-coronavirus shot protected mice from illness following exposure to SARS-CoV-2, MERS, and a bat-like coronavirus which hasn’t made the jump from animals to humans yet. Shots like this one could slow down or prevent a future pandemic.
On Tuesday, Gavi offered an overview of the dengue situation and the race for solutions to it. This year has been a record-breaking one for dengue all around the world. Bangladesh, especially, has set new numbers for deaths and cases. Dengue still has no specific treatment, even though J&J had happy trial news to report on Monday. The only available vaccine, Dengvaxia, faced a setback in 2017 when it was found to increase the risk of hospitalisations in individuals who had never been infected with dengue. Newer vaccines, like TAK-003 and TV003/TV005, are showing promise, with both expected to receive WHO prequalification by 2024. These vaccines hold the potential to combat all four dengue serotypes, a significant advancement over Dengvaxia. Local manufacturing and development, as Indonesia recently announced, will - as always - be the solution that ensures equitable access to new therapeutics in regions that are likely to need them the most.
Also, research from the Carnegie Institution for Science revealed that as climate change heats things up, higher-altitude regions will be at greater risk for algal bloom-produced toxins. Published in Nature Water, the study identified water temperatures of 20 to 25°C (68 to 77°F) as being at the greatest risk for developing dangerous levels of microcystin. Lakes hold 87% of the Earth’s surface liquid freshwater, so the effects of warming on these water bodies pose significant threats to global water quality.
On Wednesday, we learned, unfortunately, that H5N1 bird flu has flown all the way to Antarctica, raising concerns that it could kill many seals, whales, penguins, albatrosses and other rare animals and birds; it might even lead to some of them becoming extinct. Already, 30 dead birds have been found. There is also the risk of migratory birds giving the virus its first glimpse of New Zealand and Australia.
In good news on the malaria front, the WHO reported the results of a nearly 4-year long major analysis of the RTS,S, or Mosquirix vaccine. The large-scale robust evaluation of the pilot rollout of the vaccine in Ghana, Kenya and Malawi revealed a huge real-world impact. A 13% reduction in deaths in young children was attributed to the shot. The GSK vaccine also showed a 22% reduction in severe malaria in kids who were young enough to receive the three-shot series. This is despite the fact that the vaccine has been described as having only modest efficacy.
A report card of humanity’s climate response came out, and unsurprisingly, we got a big fat F on most accounts. “The 2023 state of the climate report: Entering uncharted territory” offered a glimpse of the Earth’s status on 35 climate-associated planetary vital signs. It turns out we humans have achieved record extremes on 20 measurements, including fossil fuel subsidies, ocean heat, total carbon dioxide emissions, and glacier thinning.
Yesterday, what began as a fairly eventful week started to taper off. There was news of India’s Himalaya Wellness opening a $54.4 million herbal pharma factory in Dubai.
CEPI and Emervax announced that they are partnering to advance the latter’s circular RNA vaccine technology. CEPI will provide funding of up to $2.15 million to optimise the platform and generate necessary pre-clinical data to develop vaccines against viruses with pandemic or epidemic potential.
And finally, researchers at UN University released a report warning that the world is in danger of hitting 6 interconnected risk tipping points that could have disastrous effects on human beings and the planet. They found that species are becoming extinct at ten times the natural rate due to human activities. A domino effect of extinctions could lead to ecosystem collapses. As for thresholds concerning glacier melting, those have already been crossed in some glaciers in Europe and South America, while groundwater thresholds have been surpassed in parts of Saudi Arabia. Moreover, by 2030, predictions suggest that over half a million homes in Australia will be too expensive to insure due to flooding risks. Overall, building a future we’d like is going to take a loooot of work.
Newsworthy
A threat to the world’s generics supply. Former Nigerian President Olusegun Obasanjo witnessed firsthand the groundbreaking impact of Indian generic drugs. When Nigeria was experiencing one of its worst HIV epidemics in 1999, the country could not afford HIV treatment. But when Indian generics entered the picture in the early 2000s, annual prices for HIV treatments fell from over $10,000 to about $365. By 2008, India was supplying 84% of Nigeria’s antiretroviral HIV medicines. Today, Nigeria is one of the top five importers of Indian pharma products, but it isn’t the only country that relies on India for generics. Given the lower costs of generics, Indian pharma is a lifeline for many low- and middle-income countries (LMICs). Many wealthy countries, like the UK, also purchase large quantities of generics from India. But thanks to the latter, LMICs’ lifeline could now be under threat.
Obasanjo writes in Devex about a UK-India trade deal that could hinder access to lifesaving generics in LMICs. The UK and India are entering the final stages of negotiations for a free trade agreement. As part of such a trade deal, the UK wants India to introduce sweeping changes to its intellectual property (IP) laws. These changes would go far beyond Trade-Related Aspects of Intellectual Property Rights, or TRIPS, provisions which govern global IP rules. The UK is proposing that India repeal legislation that allows patents to be challenged before they are granted or extended. Such changes would allow pharma companies to gain frivolous patents and evergreen patented medicines – like J&J tried with Bedaquiline, which is essential for the treatment of tuberculosis. Challenges to J&J’s patent applications mean that it was rejected, but if the UK has its way, that won’t be the case in the future. Overall, the measures proposed by the UK would affect India’s ability to truly be the pharmacy of the world; they would delay generic competition from entering the market and result in high costs for treatments, both of which could be catastrophic for LMICs in the Global South. In the aftermath of a global pandemic, it appears the world still hasn’t realized the importance of health equity.
(Devex)
R&D
Understanding malarial proteins. Research published yesterday in Nature Microbiology reports on the discovery of a malaria protein which helps the parasite grow inside our red blood cells. This protein, called PfAP2-P, plays a crucial regulatory role in key biological processes of malaria-causing parasites. Particularly, it helps the malaria parasite evade immune responses by synchronising its activities with those of its host during the human blood-stage of its development cycle. The researchers also identified many novel proteins which are regulated by PfAP2-P either directly or indirectly. Now PfAP2-P and these other proteins could be targeted for future therapeutic and vaccine development.
(Nature Microbiology)
You are what you eat. Bacteria-killing viruses, called bacteriophages or just phages, are being increasingly considered as alternatives to antibiotics amidst the antibiotic resistance crisis. Phage therapy is generally considered to be safe, but human cells engulf these phages when they internalise liquid from their surroundings. All this while, scientists haven’t known the full impact of this, but in a new study, researchers have made important discoveries. They found that engulfing T4 phages triggered no immune responses in human and other mammalian cells. This suggests that phages could treat inflammation-causing bacterial infections without worsening symptoms. In fact, the cells even experienced useful changes in two signalling pathways, with one boosting cell growth, survival, and proliferation and the other stalling the cell cycle just before DNA replication. In this second pathway, cells might be acting like scavengers, taking resources for their own growth from the viruses. Overall, this is a promising discovery supporting the wider use of phage therapy, though more research on different phages is required.
(PLoS Biology)
Nipping migraines in the bud. Migraine is known to be genetic, but the exact genetic bases of different subtypes of the condition have not been well understood. Now researchers from the Icelandic biopharma company deCODE genetics have identified genetic variations that appear to underlie the development of migraines. They’ve found 44 gene variants linked to the conditions, 12 of which haven’t ever been described before this. Further, a rare variant of the PRRT2 gene was correlated with a large risk of migraines with aura i.e. headaches being preceded by sensory symptoms like flashing lights or tingling in the body. Also, rare variants that suppress the function of the SCN11A and KCNK5 genes – which are involved in sodium and potassium transport between cells – seemed to protect against migraines with and without aura. The hope is that future drugs inhibiting the production of the proteins encoded by the SCN11A and KCNK5 genes could be used to treat migraines at their very source.
(Nature Genetics)
The Kibble
Wanna live longer? Walk. The notion of walking 10,000 steps a day to improve your health is popular but with no scientific basis. If it’s death from cardiovascular disease that you want to keep at bay, new research claims that just around 7,000 daily steps do the trick – though more steps pose no risk. Overall, the study led by the University of Granada provides evidence that 8,000 steps daily can significantly reduce the risk of premature death. The pace at which we walk also matters; walking fast is better than walking slow. If you’ve been struggling to meet your exercise goals, not to worry – the research indicates that for those with low levels of physical activity, every additional 500 steps also improves health.
(Journal of the American College of Cardiology)
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.