‘Health for all’ — looking at key topics in pharma for this World Health Day

As we approach World Health Day (7 April), which this year coincides with the 70th anniversary year of the World Health Organisation (WHO) and has a focus on ‘health for all’, we take a look at some key topics that have impacted pharma over the past six months…

AMR — a growing concern

Towards the end of 2017, at the launch of the AMR Centre in Alderley Park, Cheshire, concerns around the ‘lagging’ research into antimicrobial resistance (AMR) were raised by two experts in the field.

Lord Jim O’Neill, author of a landmark report on antimicrobial resistance (AMR) said that the UK government has ‘lost focus’ on the challenge over the last 18 months. He also urged big pharma to ‘do more than talk about the problem’. In his report, O’Neill predicted that antibiotic resistance will account for over 10 million deaths per year globally by 2050 and if no antibiotics are developed, the cost to the global economy of AMR would be $100 trillion by the same year.

The executive director of the new AMR Centre, Dr Peter Jackson, revealed that the number of scientists working in the industry on AMR is down on that of last year — now fewer than 500 worldwide. “The gravity of the problem is hard to overstate, and unless action is taken now it will claim many more lives than the 50,000 in Europe and the US, and the 700,000 lives across the world currently lost each year because of we’ve running out of effective antibiotics,” he emphasized.

Since then, however, there have been some more stories highlighting promising progress. For example, earlier this year, the AMR Industry Alliance released its first progress report assessing the action that has been taken to tackle AMR.

Highlights from this report included data showing that 22 Alliance companies have invested at least $2 billion in R&D dedicated to AMR-related products in 2016.

Commenting on the progress the UK BioIndustry Association (BIA) CEO and vice-chair of the International Confederation of Biotech Associations (ICBA), Steve Bates, said: “It is fantastic to see the steps that industry has taken to tackle one of the world’s most pressing public health challenges. There is a great deal of promising science being undertaken in the UK on AMR, but a lack of pull incentives is still preventing significant venture capital investment. This barrier must be removed to enable biotech companies to do more in this field. I hope to see movement from policymakers in this area in 2018.”

Also, research from a team at Rockefeller University has uncovered natural compounds in soil samples that may be useful in the treatment of several bacterial infections that have become resistant to multiple antibiotics.

In this research it was hypothesized that there could be many new calcium-dependent antibiotics housed within soil microbiomes that have not been reported in previous culture-based natural product efforts. Testing this hypothesis on thousands of soil samples, the researchers found that there were many uncharacterised antibiotic families present in the soil samples, an abundant one, found in nearly a fifth of metagenomes, they named malacidin, which on testing in animal models worked as a calcium-dependent antibiotic against MRSA.

“It is impossible to say when, or even if, an early stage antibiotic discovery like the malacidins will proceed to the clinic,” explained Dr Sean Brady, team leader at the Rockefeller University, New York, when speaking to the BBC. “It is a long, arduous road from the initial discovery of an antibiotic to a clinically used entity.”

In other research from the University of Melbourne, nanoparticles have been developed that could potentially fight some of the most dangerous antibiotic resistant bacteria.

Speaking about the research, team lead professor O’Connor said: “it was partly triggered by a collaborator who came to my lab from the US, Dr Phong Tran, who’s now at Queensland University of Technology. He has a background working with nanoparticles, and so that expertise boosted our interest and activity in that area.”

Focusing their research on antimicrobial materials that can be used within the polymer devices to stop infections from bacteria occurring, the team has uncovered the mineral selenium in the form of nanoparticles is useful for this purpose. It is believed that these nanoparticles stop bacteria growing by disrupting the surrounding membrane.

“One of the things that bacteria need to stay functioning is their cell membrane. If it starts to get holes in it or to leak, then the bacteria don’t function well and if it gets bad enough then they will die,” stated O’Connor. “One of the ways that these nanoparticles can attack bacteria is by disrupting that membrane so they make the bacteria leaky, and then things can pass in and out of the bacteria in a way they normally wouldn’t.”

Furthermore, the pharma industry as a whole have been taking steps to tackle the growing problem of AMR with many major companies committing to share ‘antibiotic surveillance data’ in a pilot project funded by the Wellcome Trust.

“Antimicrobial resistance is incredibly complex and driven by many factors — and working together across all sectors is absolutely critical to understand and control it,” explained chief medical officer, Professor Dame Sally Davies, who supports the project. “But information holds the key, so it is really pleasing to see this initiative to share information more effectively. There is an incredible amount of new and improved data being generated and this project can bring real value in making the most of existing information. Now is the time to harness that power.”

Dr Tim Jinks, Wellcome’s head of the Drug-Resistant Infections commented: “Addressing this urgent global health problem requires collective action across government, industry and civil society. We need to work together to get new treatments, but also to ensure existing medicines are used appropriately, effectively and are available to all who need them. Understanding of the spread of resistance is vital to both. This will be best achieved if information is shared and widely available.”

Influenza — a jab and a miss?

There has been a lot of coverage about influenza, the vaccination and the unfortunate fact that this latest season was a difficult one.

Discussions have flared about how the flu jab is created: Currently, WHO predicts which strains are more likely to be in circulation through various assessments of global data, leading to a level of uncertainty about efficacy, and then the vaccine is produced using the traditional egg-based approach.

Data and analytics company, GlobalData, asserted that this most recent season reinforces its belief that there should be a move away from the egg-based mass production of flu vaccines. According to the company, there are inherent limitations with the egg-based manufacturing process for vaccines that undermine the potential antibody-antigen binding affinity, which is required to achieve continued vaccine efficacy from season to season.

“In order to best facilitate this shift away from egg-based technology, governments must modernise their partnerships with vaccine manufacturers,” commented Gilbert Saint Jean, PhD, healthcare analyst at GlobalData. “Current surveillance by WHO and other institutions revolves around the 6–8 month egg-substrate vaccine timeline. Overall vaccine efficacy improves with the newer technologies if their quicker manufacturing times are combined with government-provided seed virus submissions from increased surveillance at the global level for mutations in the antigenic target of flu vaccines.”

Alternative manufacturing approaches (cell-based and recombinant) are available and can directly incorporate the sequenced circulating flu viruses and can do so more quickly that the egg-based approach.

Moreover, GlobalData has also recommended that quadrivalent vaccines be used (in particular on the NHS) as these offer further protection against a fourth flu strain (‘Japanese flu’), which is becoming most prevalent in Europe.

And, with a potential ‘universal’ flu vaccine in the second phase of clinical study — Vaccitech’s jab, which stimulates the immune system to boost influenza-specific T-cells rather than antibodies — more cards are being turned over in the potential options available to patients.

HIV/Aids — resistance on the rise

Late last year, a meta-analysis published in The Lancet Infectious Diseases showed that HIV drug resistance is on the rise.

The study, performed by researchers at University College London (UCL) and WHO, evaluated over 350 datasets, which included the data from 56,044 adults who were at the start of first-line therapy for HIV between the years of 1996–2016. It was revealed that resistance – particularly to one of the main types of first-line drug, non-nucleoside reverse transcriptase inhibitors (NNRTIs) — is on the rise. Additionally, those who exhibited drug resistance were more likely to have previously been exposed to antiretroviral drugs, often during pregnancy.

“Treatments for HIV have improved immensely in recent years, and close to 21 million people worldwide are now being treated with antiretroviral therapy. Yet to end the AIDS epidemic as a public health threat, minimising drug resistance will be one part of the response. Our findings show the importance of improving how we monitor drug resistance, and suggest we should review which drugs are included in first-line therapies,” said the study’s lead author, Professor Ravindra Gupta (UCL Infection & Immunity).

“If we are to combat HIV drug resistance, we must ensure countries can do a good job in monitoring and responding to it when needed,” added co-author Dr Silvia Bertagnolio of WHO. “New WHO guidelines and a global action plan aim to help make this happen.”

In other research, early this year, from a team based in the US, it has been revealed that a form of engineered stem cell-derived chimeric antigen receptor (CAR) T-cells may be useful in the long-term suppression of HIV.

This study, which involved haematopoietic stem/progenitor cells (HSPCs) in a primate model demonstrated that CD4 protected T-cells have the potential for long-term binding allowing an immune memory-like response.

“The demonstration here that stem cells can be engineered to respond to AIDS virus-infected cells in an animal model is an impressive first step for harnessing the immune system to target HIV,” said Dr Bruce Walker, director of the Ragon Institute of MGH, MIT, and Harvard, when speaking about the study to STAT(he was not involved in the study group). “The effect at this point is modest, but clearly gives us something to build on.”

The major advantage of engineering stem cells that creates T-cells (rather than the T-cells themselves) is that an unlimited number of T-cells that can attack the virus can be produced. This may be the vital factor to how this form of therapy can work effectively to treat and potentially eradicate HIV, although as the researchers noted more work is required.

And, in looking at prevention of the disease global pharma company, Mylan, revealed its deliverance of the world’s largest pre-exposure prophylaxis (PrEP) implementation trial, which will target an estimated 10,000 high risk people.

The three-year trial, which will be funded by NHS England, is designed to assess the full additional potential of PrEP by gathering clinical evidence on optimal targeting, update and implementation on a large scale.

“The impact of this complex illness has been widespread and devastating; more than 70 million people have been infected and 35 million have died from HIV since the epidemic began,” said president of MylanEurope, Jacek Glinka. “We all know the saying ‘prevention is better than cure’ and this is never more true than when we discuss HIV and AIDS. The NHS PrEP trial offers hope, not only to those participating in the trial, but for the millions around the world who stand to benefit from the results. While treatment for those living with HIV is crucial, the importance of breaking new ground with preventative medication to reduce infection rates can’t be underestimated. We see this trial as a huge step forward in the battle against HIV and are delighted to be involved.”