Signs of progress against the superbugs, but not yet at the scale needed: Study

A core group of pharmaceutical companies are making progress in tackling the spread of anti-microbial resistance, new findings from the 2020 Antimicrobial Resistance Benchmark indicate. However, although a few companies are expanding their efforts, change is not happening at the scale needed to radically impact the threat from drug resistance.

The 2020 Antimicrobial Resistance Benchmark, published finds that more companies are moving to discourage the overselling of their antibiotics and antifungal medicines to doctors and other healthcare professionals. Most companies have a strategy to prevent antibacterial residue being released in factory wastewaters. Furthermore, pharmaceutical companies are sharing more data on where drug resistance is emerging.

Compared to 2018, the pipeline for priority bacterial and fungal infections remains small, with only 51 candidates in late-stage clinical development. Only a handful more clinical-stage antibiotics are supported by plans to ensure they are available and used wisely soon after launch. Moreover, antibiotics are not being made widely available in low- and middle-income countries through registration filings or supply strategies.

“With older antibiotics unavailable in low- and middle-income countries, there is little guarantee that new ones will reach the people who need them. Such ‘access gaps’ can lead people to misuse antibiotics. Pharma companies must address access to protect the effectiveness of their medicines,” said Jayasree Iyer, Executive Director of the Access to Medicine Foundation, which publishes the Antimicrobial Resistance (AMR) Benchmark.

1,521 products; 40 per cent of the pipeline

The AMR Benchmark is an independent report that is published every two years, comparing how a cross-section of the pharmaceutical industry is responding to the threat from drug-resistant infections. It measures 30 companies with a major stake in the anti-infectives market, including multinational pharmaceutical companies, biotechnology firms and manufacturers of generic medicines. These are among the last companies to remain committed to developing and producing these products. They have at least 1,521 antibacterial or antifungal medicines or vaccines on the market and account for almost 40 per cent of antibiotics in development.

Stats show resistance on the rise

The low profitability of antibiotics is leaving the world precariously reliant on just a handful of pharmaceutical companies to develop and manufacture them. Since the 2018 AMR Benchmark, two more companies – Novartis and Sanofi – have retreated from new antibiotics R&D, while two further companies – Achaogen and Melinta – have filed for bankruptcy.

The most recent statistics show the scale of the problem. Antibiotic and antifungal resistance is estimated to kill 35,900 people in the US alone each year. In the EU/EEA, resistance accounts for at least 17 per cent of infections, and AMR is responsible for 33,000 deaths each year. In India, resistance exceeds 70 per cent for many widespread bacteria.

What is less well-known is that more people today die from a lack of access to medicine than from drug-resistance. This means improving access to medicines that still work is even more essential, while prudent use is essential for ensuring medicines keep working for as long as possible.

How are companies doing on AMR since 2018?

Three companies are identified as leaders in 2020 – GSK, Entasis and Cipla – which are followed closely by a few strong performers. GSK has the biggest pipeline, and is developing the bulk of new vaccines. However, it has regressed in some areas since 2018, while others have improved. Pfizer, for example, now leads in terms of stewardship, and is the first pharmaceutical company to publicly share its raw surveillance data. Johnson & Johnson performs strongly for the second year, largely for its actions to improve access to treatment for tuberculosis (TB).

Entasis focuses its R&D exclusively on bacteria in the highest threat category, including A. baumannii, which can cause severe drug-resistant infections such as pneumonia, septicaemia and meningitis. Cipla is one of the three companies in 2020 to fully decouple its sales agents’ bonuses from sales volumes, a significant step in mitigating against overselling.

Manufacturers of generic medicines are starting to get involved in innovation and access. Mylan has licensed TB treatment delamanid from Otsuka for South Africa, India and other high-burden countries; Cipla bought the antibiotic plazomicin from Achaogen; and Teva reports strategies for pricing and to ensure supply.

Meanwhile, financial support for antibacterial R&D has brought smaller R&D-focused enterprises and biotechs into the field. These companies have some of the most innovative medicines in development, such as ridinilazole from Summit, which targets C. difficile. However, such companies can normally only take on the earlier stages of development and lack of investment to progress the candidates has meant that projects are stalling and not getting to the market.

“This second benchmark provides a reality check. The progress we see is being overshadowed by our increasing reliance just a handful of companies. We can’t take their commitment for granted. It is not too late to prevent irreparable damage to the global supply of antibiotic medicines and vaccines,” says Iyer.

Findings in brief

Antibiotics are not being made widely available in low- and middle-income countries through registration filings or supply strategies: only three of the 13 on-patent antibiotics in this analysis are filed for sales registration in more than 10 of the 102 countries where better access is urgently needed; and when it comes to older, but still useful, antibiotics, companies are supplying just 14 of 30 so-called “forgotten” antibiotics to low-income countries.

10 companies are either decoupling bonuses from sales volumes or refraining from deploying sales agents for antimicrobials. This compares with five companies in 2018. One company (Teva) sets a new best practice by not having a sales force to promote any of its antibacterial or antifungal medicines. By decoupling bonuses from sales volumes, or not using sales staff, companies mitigate against overselling antibiotics and driving resistance.

A new standard has also been set when it comes to companies sharing what they know about the spread of resistance, with Pfizer becoming the first to share raw data from a surveillance programme in an open-access online register. Hospitals and governments need to know where resistance is developing so they can adapt treatment guidelines.

Since 2018, a few more clinical-stage antibiotics are supported by plans to ensure better access and good stewardship soon after launch: eight candidates out of 32, compared with two out of 28 in 2018 (25 per cent up from seven per cent). However, the development of such plans remains patchy. Planning ahead while R&D projects are in clinical development accelerates access and stewardship for successful candidates after launch.

Companies’ environmental risk-management strategies for minimising the impact of their manufacturing processes on resistance are more comprehensive than in 2018. Most companies are now requiring third-party suppliers to meet comparable standards. Releasing manufacturing waste into the environment can contribute to AMR, as bacteria present in water and soil are exposed to antibacterial ingredients, which can trigger the emergence or selection of resistance genes.

On  23rd January, the 2nd AMR Benchmark report will be presented for the first time at a dedicated session at the 2020 WEF Annual Meeting in Davos. The session will be opened by Bruno Bruins, Dutch Minister for Medical Care, and moderated by Professor Dame Sally Davies, UK Special Envoy on AMR and co-convener of the UN Interagency Coordination Group on AMR.

During the 2020 WEF Annual Meeting, the Benchmark will be presented in an Affiliated Session titled “Securing the Future of Healthcare Through Access to New and Essential Antibiotics: The 2020 Antimicrobial Resistance Benchmark.”

The high-level roundtable will feature the results of the 2nd AMR Benchmark report, showing how leading pharmaceutical companies are tackling drug-resistant infections. Participants will then discuss how governments, investors, companies and civil society organisations can work together to revitalise the current infrastructure that develops and deploys new and essential antibiotics for patients. The session will also include the announcement of the ‘Investor Year of Action on AMR’.

The session will be opened by Mr Bruno Bruins, Dutch Minister for Medical Care, and moderated by Professor Dame Sally Davies, UK Special Envoy on AMR and co-convener of the UN Interagency Coordination Group on AMR.