How successful has the BEAM Alliance Initiative and biopharma been at addressing Antimicrobial Resistance (AMR)?

The AMR global threat

Antimicrobial resistance (AMR) has long been recognised as a global epidemic but it is only relatively recently that it has been accepted by worldwide governments as a global public health crisis and an urgent threat. Today, an estimated 700,000 people die each year because of the growing number of potentially deadly infectious pathogens. These include pathogens that cause tuberculosis, HIV, malaria, and staphylococcus infections which have developed resistance to current treatment regimens. AMR therefore has the potential to turn back the clock on modern medicine.

At the current rate, annual deaths due to AMR is expected to reach 10 million by 2050 globally, with an estimated economic cost of $100 trillion.¹ The awareness of AMR in the political sphere was largely spurred by efforts in the Unites States and Europe, particularly in 2016, with the United Nations declaration on AMR and a communication from the G20 Summit. Additionally, in 2016 the Davos Declaration clearly demonstrated the commitment of the pharmaceutical industry to combating the challenge of AMR with signatures by over 100 companies and organisations.

Challenging the threat

Combating AMR requires an approach that enables sustainable use of antimicrobials, prevents and controls infections, preserves the effectiveness of existing therapies and incentivises the innovation of new therapies and diagnostic tools. To overcome some of these challenges it is necessary to create new global incentives to drive the innovation of novel new agents. Currently the antibacterial therapeutic area is recognised to be the most underserved segment of the pharmaceutical industry. Unfortunately, the past few years have seen a decrease in the investments in research and discovery for innovation in AMR, this is largely due to the low return on investment for the pharmaceutical industry which is predominantly due to three key reasons:

• AMR products have costly R&D which results in high launch prices to make them commercially viable
• Good stewardship programmes will position new, innovative anti-microbial agents as “last line” rescue therapies to preserve their efficacy and reduce the risk of drug resistant pathogens developing
• The clinical study programmes for new anti-microbial agents are usually for regulatory approval purposes and therefore compare to existing standard of care (SoC), only powered to demonstrate non-inferiority. As the SoC are predominantly older and inexpensive agents, building robust dossiers for positive outcomes in health technology assessments is challenging as the HTA bodies assessment methodologies are not well suited to confirming the wider public health value new agents offer to AMR. They expect superiority to be demonstrated, a few countries (e.g. England, France, Germany, Norway, Sweden) have taken steps to get their HTA systems to begin to address these issues but it is very much work in progress

For this reason, few large pharmaceutical corporations are actively involved in innovative R&D efforts. Research leads us to believe that the antibiotic development pipeline may have been re-energised. However The Pew Trust estimates that as of March 2017 there are 39 antibiotics in Phases I to III of the development pipeline, unfortunately further investigation reveals that this pipeline is not robust enough to address the current and projected clinical need.^2-3 The potential success rate of moving an antibiotic through the different clinical phases suggests that of these 39 drugs in development, only 13 (33%) will achieve a marketable product status.⁴ Also, most new antibiotics do not have the novel mechanisms of action necessary to significantly ensure effectiveness against resistant pathogens⁵ because the majority of these products are redevelopments or combinations of existing compounds.

An initiative driving for change in AMR – The BEAM Alliance

The challenges associated with combating AMR are not insignificant and require a new paradigm to incentivise and encourage new products in this space. One initiative looking at overcoming the hurdles of novel antimicrobial research and development is the BEAM Alliance (Biotech companies in Europe combating anti-microbial Resistance). Launched in June 2015, the BEAM Alliance is a strong network of approximately 100 small and medium-sized European biopharmaceutical companies committed to developing innovative products to fight antibiotic-resistant pathogens.

The purpose of the of the BEAM Alliance is to enable innovation in AMR research by:

• Giving its members a unique voice to propose and support policies and incentives to identified issues, especially in Europe,
• Collaborating with existing community of stakeholders dedicated to implementing tangible solutions,
• Recommending bold incentives that warrant action by policymakers to stimulate innovation

In just 2 years of existence, the BEAM Alliance has become the major contact for policy makers when it comes to the dialogue with SME’s developing innovative products to fight against AMR.

The BEAM Alliance was a key influencer in the Davos declaration and in outlining the challenges associated with combating AMR from an industry perspective.

The recent BEAM Alliance Position Paper called out for worldwide stakeholders to support SME-driven innovation and revive the product pipeline fighting antimicrobial resistance.

This document lists ten guidelines as to how antibacterial R&D could be revived and proposes specific support for SME-driven innovation in the AMR field. The alliance particularly demands that policymakers understand the specific nature and needs of SMEs to design effective PUSH and PULL mechanisms.

• Adequately-shaped incentive mechanisms that ultimately rewards R&D evidence
• Health Technology Assessment recognising the true value of SME innovation
• Dedicated regulatory pathways to support the specific needs of AMR projects and act as pre-qualification criteria to some PUSH/PULL incentive mechanisms
• PUSH incentives and funding mechanisms that are directed to SMEs, calibrated and accessible for SMEs in practice
• Calibrated Market Entry Rewards (MER) to ensure continuous and sustainable innovation from academics to biotech companies and to large pharma players
• R&D prizes and phase entry rewards as effective PULL mechanisms for SMEs to incentivise the most underserved indications in AMR
• Targeted tax incentives specifically addressing SMEs to incentivise private investments into AMR-focused companies and/or avoid de-prioritization
• Going beyond to exploit all possibilities for AMR from SMEs
• Support education to strengthen attractiveness of the field for R&D professionals/scientists
• Long term thinking and wisely usage of AMR innovations combined with appropriate diagnostics development

Over USD 2 billion in R&D has been dedicated to developing innovative products to tackle anti-microbial resistance, including small molecule antibiotics, biologics and products with a prophylaxis indication, since 2016 by the BEAM Alliance members and together they have over 120 potential new antibiotic compounds or curative and preventive technologies in the research pipeline. Of these, the majority target critical pathogens as mentioned by the WHO priority list and approximately 80% investigate new mechanisms of actions or new targets, thus representing a high diversity of innovative approaches to fight AMR. The next step will be for HTA bodies and payers to work more closely with the pharmaceutical industry to ensure new antibiotics are not only evaluated for their individual value but also their wider societal impact and value on combating AMR thereby rewarding manufacturers for the risks they take to bring these needed therapies to patients.

Initiatives like the BEAM Alliance are crucial in the battle against AMR because failure to act now presents an unthinkable scenario where antibiotics no longer work, and the world is cast back into the dark ages of medicine where treatable infections and injuries are fatal once more.

References

1. The Review on Antimicrobial Resistance. Antimicrobial resistance: tackling a crisis for the health and wealth of nations, London UK, 1–20
2. The Boston Consulting Group. Breaking through the wall: enhancing research and development of antibiotics in science and industry, Berlin DE
3. Antibiotics Currently in Clinical Development, The Pew Trust
4. Stern, S., C. Call for Concerted Action on Antibiotics Research and development, The Boston Consulting Group, Berlin, (2017)
5. Renwick, M. J. Targeting innovation in antibiotic drug discovery and development: the need for a one-health, one-Europe, one-world framework. European Observatory on Health Systems and Policies, London, UK, Health Policy Series