Elcin Barker Ergun
CEO, MENARINI Group
Dr Henry Skinner
CEO, AMR Action Fund
Dr. Najy Alsayed
Global Therapeutic Area Head for Infectious Diseases, MENARINI Group
Antimicrobial resistance (AMR) to antibiotics is one of the three most critical threats to patients’ lives, and it continues to grow on a global scale.
Published data by the World Health Organization indicates that bacterial AMR is associated with 4.95 million deaths worldwide, with 1.27 million of those deaths directly attributable to AMR. Failure to immediately and decisively act on this devastating threat will lead to a projected USD 2.9 trillion cumulative loss in OECD countries and 10 million deaths globally by 2050.
Maintaining resilience against antibiotic resistance
Elcin Barker Ergun, CEO of pharmaceutical company MENARINI Group, insists that a decisive pharma contribution must tackle both the need to boost the AMR antibiotics pipeline and increase patient access to such novel antibiotics.
“One cannot highlight enough, the criticality of securing patient access to novel antibiotics and the major challenges we are currently facing in achieving this fundamental goal. Only two AMR antibiotics out of the 16 developed and approved during this last decade were accessible to clinicians and patients even in the 14 highest-income countries,” she says. “This has resulted in a continued and large use of older antibiotics as the first treatment option. It was also associated with the bankruptcy of most biotechs involved in the development of those 16 novel AMR antibiotics alongside drastic loss of interest and investment in this therapeutic area.”
MENARINI, a global Pharma 50 company headquartered in Italy is one of the few investing in the development and availability of novel antibiotics for clinicians and patients alike. In this challenging context, it strives to maintain a bold and leading role in the fight against AMR.
Defining antibiotic access models across Europe
Ergun insists that to tackle AMR, all key stakeholders need to collaborate to build a sustainable model, which supports the development of novel antibiotics and ensures patient access. “Successful models that created the right incentives, such as the Orphan Drug Designation, resulted in many orphan drugs being developed, approved and made accessible to clinicians and patients by pharma companies in the last years.”
Given the growing threat of AMR and consistent reports highlighting the devastating consequences to humanity, Ergun explains that, within the context of the current revision of the EU legislation, an AMR designation for new antibiotics at a European level, can provide a similar efficient solution. Each country can then adopt complementary and locally fitting models such as the UK-Delinking-2 model, the Swedish procurement model or an orphan diseases-like model.
In all cases, this overarching designation will provide clear guidance that countries must recognise and define a better patient access model for their population.
Why global antibiotic R&D is broken
However, the marketplace for antimicrobial research and development (R&D) has been broken for decades, says Dr Henry Skinner, CEO of the AMR Action Fund, which aims to bring two to four new antibiotics to patients by 2030.
“Only a fraction of Phase I and II candidates achieve late-phase development, let alone find their way to the patients who need them,” says Dr Skinner. “The financial equation for antimicrobial development shoulders much of the blame. It can cost more than a billion pounds, accumulated over a decade of effort to bring a drug to market. Yet, annual sales might achieve just a few million pounds.
“This poor return on investment is why private investors avoid antibiotics and direct investment goes towards other therapeutic areas such as obesity and cancer, yet antimicrobials — which underpin modern medicine — receive a fraction of the financial lifeblood for a small biotech company.”
A pull incentive that is not adequately sized is like building a bridge partway across a ravine. You have advanced, but you’ve not actually gotten anywhere.
Dr Henry Skinner
Driving towards a sustainable market
The AMR Action Fund is a public-private partnership with nearly $1 billion in resources, charged with supporting smaller biotech companies through the late-stage development phases. The Fund exists to ensure that vital R&D continues as governments take the critical steps needed to improve market conditions and convince investors to return to the space.
“If governments don’t act, and the financial landscape remains unchanged, we are staring down a future with millions of lost lives and billions of pounds spent globally each year in incremental healthcare expenditures due to AMR,” explains Dr Skinner.
Value of effective pull incentives for antibiotic R&D
“We applaud NHS England for introducing pull incentives in the form of a subscription model that delinks the volume of drugs sold from the rate of reimbursement — vital for preserving the efficacy of next-generation antimicrobials,” says Dr Skinner. He also cites the US’s consideration of its own subscription scheme through the PASTEUR Act, which Congress reintroduced this year.
Across Europe, Canada and Japan, governments are exploring these incentive models tailored to their countries’ needs. However, what is essential is its size and timeliness. “A pull incentive will invigorate the market only if it is commensurate with the investment required of new drugs. A pull incentive that is not adequately sized is like building a bridge partway across a ravine. You have advanced, but you’ve not actually gotten anywhere,” he explains.
AMR will continue to spread without adequate and decisive solutions
When asked why we witness a continuous spread of AMR, Dr. Najy Alsayed — Global Therapeutic Area Head for Infectious Diseases at MENARINI Group — says that there are numerous factors. However, he proposed focusing on two main drivers: (1) The natural ability of bacteria to adapt and develop a mechanism of resistance; and (2) The sub-optimal efficiency of current antibiotics policies based on restricted patient access and low recognition of economical and clinical contributions of the life-saving capability of novel antibiotics.
“Considering the first driver, we can start by stressing the fact that antibiotic resistance occurs when bacteria change so that antibiotic medicines can no longer kill them or stop their growth,” says Dr. Alsayed. “This associated bacterial ability materialises through two main mechanisms. The first one is a mutation in their genes, allowing some bacteria to survive antibiotics. This antibiotic-protective genetic mutation is then passed along. The second mechanism is called horizontal gene transfer, involving genetic material moving from antibiotic-resistant bacteria to other bacteria.”
He explains that this is why antibiotics must be continuously developed. We need an appropriate flow of novel antibiotics that addresses the two mechanisms associated with bacterial resistance.
Reliance on existing antibiotics
Dr. Alsayed states that current strategies used to fight AMR are much focused on simply restricting the use of novel antibiotics.
However, it is worth noting that this novel antibiotics restricted patient-access has resulted in an increased level of resistance to older antibiotics which continues to be routinely largely used, with clinicians and patients strapped for choice.
“This has led to broken development and an unsustainable patient access economic model for antibiotics,” says Dr. Alsayed. “Therefore, the continuous spread of antibiotic resistance — with alarming projections of up to 10 million deaths by 2050 — has prompted the need to consider new approaches and potential solutions.”
Comprehensive approach: involving and empowering patients
A comprehensive approach involving antimicrobial stewardship, regular diagnostic testing, preventive healthcare measures and the use of medical technologies to prevent and best manage infections is essential to address the challenges of AMR.
The AMR Patient Group stands for increasing awareness among patients about the associated risks of antibiotic misuse, the currently limited effective infection prevention measures, as well as the imperative of securing appropriate patient access to existing and novel antibiotics. Its unique position in collaborating with patients has provided insight into how lives have been turned upside down because of resistant bacteria.
The key objective and contribution lie in closing the awareness gap among patients, healthcare professionals and policymakers about the impact of antibiotic resistance on patients’ lives, the need to increase efforts to develop novel antibiotics alongside the imperative of responsible access and use of such antibiotics. The role of the patient in achieving these objectives is paramount, and they should be associated with all efforts every step of the way.
The AMR Patient Group believes that, in this fight against AMR, several consolidated actions must be deployed to efficiently protect patients against such an immediate threat. These include clear governance arrangements and decisions; spreading awareness and urgency to act now; improving prevention and control measures; encouraging investment in new antibiotics R&D; and appropriate patient access to such novel antibiotics and targeted medical technologies for hospitals.
Everyone in the decision-making seat (governments, policymakers, hospital managers, etc.) need to commit to these goals and make appropriate decisions to protect all citizens, as we are all at risk of becoming AMR patients.
With the One Health approach linking human, animal and environmental health, the need for consolidated efforts to address drug-resistant infections requires immediate and cross-disciplinary commitments since these can easily cross from animals to humans. The same urgency applies to the spread of superbugs across borders.
Developing actionable initiatives against AMR
The urgent need for new solutions is also made necessary by the dwindling novel antibiotics portfolio alongside a worrisome reduction in the number of pharmaceutical companies and investment funds involved in AMR.
“We strongly believe that we all need to work towards recognising the devastating consequences of antibiotic resistance and the imperative for an appropriate and decisive solution,” adds Dr. Alsayed. How can this be done? Ergun says AMR designation can be one way forward, which recognises both the specificity of antibiotic resistance challenges and the life-saving contribution of novel antibiotics. This is particularly essential among vulnerable patients, such as those undergoing transplantation, oncology treatments or major surgery, she explains.
“The ongoing UK patient access ‘Delinking 2’ initiative is a very welcomed contribution translating this into a concrete solution adapted to UK needs and constraints. A similar approach was initiated through the Swedish model. This can also be applied at a European level, leveraging the current revision of the EU legislation and building on the successful EU experience, centrally creating the orphan disease designation model and providing guidance to each country,” concludes Ergun.