World Health Day: We celebrate global drug discovery


As we celebrate World Health Day, Lu Rahman looks at some of the key drug discovery and development successes over the last year that have significantly helped improved the health and wellbeing of the global population.  

Malaria breakthroughs 

According to The World Health Organization (WHO) more than a million people in Africa die from malaria every year, including 3,000 children each day. Last year saw some key breakthroughs in the fight against this disease. These included a new monoclonal antibody discovered and developed at the National Institutes of Health (NIH); it was found that one dose safely prevented malaria for up to nine months in people who were exposed to the malaria parasite. A clinical trial last year was the first to demonstrate that a monoclonal antibody can prevent malaria in people.  

“Malaria continues to be a major cause of illness and death in many regions of the world, especially in infants and young children; therefore, new tools are needed to prevent this deadly disease,” said NIAID Director Anthony S. Fauci. “The results reported suggest that a single infusion of a monoclonal antibody can protect people from malaria for at least nine months. Additional research is needed, however, to confirm and extend this finding.”  

Just under year ago Researchers at the Francis Crick Institute and the Latvian Institute of Organic Synthesis designed a drug-like compound which effectively blocks a critical step in the malaria parasite life cycle and are working to develop this compound into a potential first of its kind malaria treatment. 

While drugs and mosquito control have reduced levels of malaria over recent decades, the parasite still kills over 400,000 people every year, infecting many more. Worryingly, it has now developed resistance to many existing antimalarial drugs, meaning new treatments that work in different ways are urgently needed. 

“Malaria parasites invade red blood cells where they replicate many times, before bursting out into the bloodstream to repeat the process. It’s this cycle and build-up of infected red blood cells which causes the symptoms and sometimes fatal effects of the disease,” said Mike Blackman, lead author and group leader of the Malaria Biochemistry Laboratory at the Crick. “If we can effectively trap malaria in the cell by blocking the parasite’s exit route, we could stop the disease in its tracks and halt its devastating cycle of invading cells.” 

The compound works by blocking an enzyme called SUB1, which enables malaria to burst out of red blood cells. Existing antimalarials work by killing the parasite within the cell, so the researchers hope this alternative drug action will overcome resistance. Importantly, the compound can also pass through the membranes of the red blood cell and the compartment within the cell where the parasites reside. 

Another step forward came as The WHO recommended GlaxoSmithKline (GSK)’s RTS,S malaria vaccine to be given to children living in sub-Saharan Africa who are at risk of contracting Malaria.  

RTS,S is the first and only malaria vaccine to have been shown in pivotal long-term clinical trials to significantly reduce malaria in children. The vaccine is the result of over 30 years of research led by GSK, with Path, a global non-profit dedicated to ending health inequity, as well as other partners.    

Thomas Breuer, Chief Global Health Officer, GSK, said: “GSK is proud that RTS,S, our groundbreaking malaria vaccine, developed over decades by our teams and partners, can now be made available to children in sub-Saharan Africa and other regions with moderate to high malaria transmission. This long-awaited landmark decision can reinvigorate the fight against malaria in the region at a time when progress on malaria control has stalled. Both real world evidence and clinical trial data show that RTS,S, alongside other malaria prevention measures, has the potential to save hundreds of thousands of lives.”  

More recently, according to the Medicines for Malaria Venture (MMV), the Australian Therapeutic Goods Administration (TGA) has approved the use of single-dose Kozenis (tafenoquine) in children aged two years and above in combination with chloroquine for the radical cure (prevention of relapse) of Plasmodium vivax (P. vivax) malaria.  

The approval includes a novel, 50 mg dispersible tablet that can be dispersed in water and which was developed by GSK in partnership with MMV to facilitate use in children, who are disproportionately affected by the disease.  

“We are proud to have worked with GSK to develop this child-friendly treatment and are thrilled by today’s announcement. P. vivax malaria is particularly dangerous for young children for whom repeated relapses can lead to cumulative severe anaemia and, in some cases, be fatal. Today, we have a tool to put a stop to the relentless relapse both for adults and children – we are one step closer to defeating this disease.” said Dr David Reddy, Chief Executive Officer of MMV.     

HIV developments 

There has been considerable progress in tackling HIV of late. Earlier this year an experimental HIV vaccine based on mRNA showed promise in mice and non-human primates, according to scientists at the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health.  

The results, published in Nature Medicine, showed that the novel vaccine was safe and prompted desired antibody and cellular immune responses against an HIV-like virus. Rhesus macaques receiving a priming vaccine followed by multiple booster inoculations had a 79% lower per-exposure risk of infection by simian-human immunodeficiency virus (SHIV) compared to unvaccinated animals. The research was led by Paolo Lusso of NIAID’s Laboratory of Immunoregulation, in collaboration with other NIAID scientists, investigators from Moderna and colleagues at other institutions. 

“Despite nearly four decades of effort by the global research community, an effective vaccine to prevent HIV remains an elusive goal,” said NIAID Director Anthony Fauci, Chief of the Laboratory and a paper co-author. “This experimental mRNA vaccine combines several features that may overcome shortcomings of other experimental HIV vaccines and thus represents a promising approach.” 

mRNa technology has become a key technology in drug development – as shown through the recent trial launched of HIV vaccine antigens delivered through mRNA technology. 

IAVI and Moderna have announced that first doses have been administered in a clinical trial of experimental HIV vaccine antigens at George Washington University (GWU) School of Medicine and Health Sciences in Washington, DC.  

The Phase I trial, IAVI G002, is designed to test the hypothesis that sequential administration of priming and boosting HIV immunogens delivered by messenger RNA (mRNA) can induce specific classes of B-cell responses and guide their early maturation toward broadly neutralising antibody (bnAb) development.  

The induction of bnAbs is widely considered to be a goal of HIV vaccination, and this is the first step in that process. The immunogens being tested in IAVI G002 were developed by scientific teams at IAVI and Scripps Research and will be delivered via Moderna’s mRNA technology.  

“We are tremendously excited to be advancing this new direction in HIV vaccine design with Moderna’s mRNA platform. The search for an HIV vaccine has been long and challenging, and having new tools in terms of immunogens and platforms could be the key to making rapid progress toward an urgently needed, effective HIV vaccine,” said Mark Feinberg, President and CEO of IAVI. “We are grateful to all of our partners and especially to the Bill & Melinda Gates Foundation for funding this trial.”  

Meanwhile,  the US Food and Drug Administration (FDA) recently  approved a long-acting HIV prevention medication for the first time. Developed by ViiV Healthcare, the medicine is long-acting cabotegravir injected once every two months. The FDA has approved the medicine for use by adults and who are at risk of sexually acquiring HIV.   

This milestone marked a vital expansion of biomedical HIV prevention options available to people in the United States. An estimated 34,800 people in the United States acquired HIV in 2019, the most recent year for which data are available.  

Until this approval, the only FDA-licensed medications for HIV pre-exposure prophylaxis (PrEP) were daily oral pills containing the HIV drugs tenofovir and emtricitabine. These medications are highly effective at preventing HIV when taken daily as prescribed. However, taking a pill daily while feeling healthy can be challenging. Long-acting injectable cabotegravir PrEP is a less frequent, more discreet HIV prevention option that may be more desirable for some people.   

Covid-19 – the legacy 

With much of the world having had the opportunity to be jabbed and boosted (although wider distribution of vaccines still needs to be addressed) we are well aware of the effort and collaboration that occurred to bring multiple Covid-19 vaccines to market. So rather than focus on these vaccines, here’s a taster of other developments that have occurred as a result of research and discovery in this field.  

One key milestone was for those who can’t be vaccinated. AstraZeneca’s Evusheld (tixagevimab co-packaged with cilgavimab) was authorised by the Medicines and Healthcare products Regulatory Agency (MHRA) and is the first antibody combination for pre-exposure prophylaxis (PrEP) against Covid-19 licensed in Great Britain.   

The use of this medicine is for adults who are not currently infected with (or know exposure to) the Covid-19 virus and are unlikely to mount an adequate response to Covid-19 vaccination – including those for whom vaccination is not recommended. 

About 500,000 people in the UK are immunocompromised and may benefit from this medicine for pre-exposure prophylaxis of Covid-19. Nearly 40% of people with immunocompromised or immunosuppressed conditions mount a low or undetectable immune response after vaccination and approximately 11% fail to generate any antibodies. This includes people with blood cancers, those taking immunosuppressive drugs after an organ transplant or for conditions including multiple sclerosis and rheumatoid arthritis. 

Tom Keith Roach, President of AstraZeneca UK, said: “Evusheld fills an urgent gap in the UK’s fight against Covid-19, providing protection for people for whom vaccination may not be effective and who are often amongst the most clinically vulnerable in society. We hope to see this critical medicine made available to UK patients as quickly as possible, in line with other countries.”  

Hugh Montgomery, Professor of Intensive Care Medicine at University College London, said: “This announcement is really good news. Sensible public health actions with vaccination are the mainstay of protection for most individuals in the UK. However, for a considerable number in society with existing health problems, protection against the virus through vaccination is limited. Availability of this antibody medicine now offers an increased likelihood of pre-exposure protection, and all from a single, effective immunisation that can last for months.”  

Meanwhile, we learned about a Covid-19 study which boosts a Swedish rheumatoid arthritis programme. Cyxone, a Swedish clinical stage biotech company developing disease modifying therapies for diseases such as rheumatoid arthritis (RA), confirmed the previously demonstrated favourable safety and tolerability profile for its drug candidate Rabeximod, in the Clinical Study Report from its exploratory Phase II study in Covid-19 patients.    

Other observations include a trend showing patients that were given Rabeximod, in comparison to the placebo group, had a higher rate of early release from the hospital. Exploratory endpoints analysis indicated modulation of disease relevant cytokine biomarkers by Rabeximod compared to the placebo group. These results are encouraging and will be further investigated in the upcoming RA trial. The study also supported the dose selection for the upcoming RA study.  

The Phase II Covid-19 study was carried out during the pandemic in 2020 and 2021, in order to support the global effort in identifying a drug for a new and unexplored severe disease. The study was designed in accordance with FDA’s guidelines for Covid-19 studies.   

CEO Tara Heitner said: “I am pleased to see that Rabeximod is safe and well-tolerated in this group of Covid-19 infected patients and I am very encouraged by the additional supportive observations. Safety and tolerability are crucial in all our clinical work. Data from this trial adds to the data we have collected historically in patients with rheumatoid arthritis, our primary indication for Rabeximod. We will now focus our resources for Rabeximod in the upcoming Phase 2b study regarding rheumatoid arthritis. I’m proud that Cyxone took on the challenge and contributed to the global work of finding a drug for Covid-19.”  

Other interesting work in this area includes Oragenics’ collaboration with KBI Biopharma for an intranasal vaccine candidate; the possibility of a plant-based therapy for Covid-19 from Novel Concepts Medical, and the increasing exploration of mRNA technology in drug development for treating life-threatening acute and chronic conditions.

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