Pharma shows bright points of progress against AMR, yet lags on access to antibiotics

• Big Pharma’s engagement with antibacterial and antifungal R&D appears to have stabilised.

• Generic medicine manufacturers are also improving, for example, by licensing their own on-patent antibiotics to new partners to boost supply and global access.

• There is a worrying lack of momentum in making the right antibiotics accessible for people in low- and middle-income countries, where the risk of drug-resistant infections is highest.

Good practice is becoming more common in the actions taken by pharmaceutical companies to limit the threat of antimicrobial resistance (AMR). This is most notable in the plans to ensure wider access to and responsible use of future products, as well as in the steps taken to curb the release of antibiotic waste into the environment. In stewardship, generic medicine manufacturers are taking a more active role. However, all companies miss opportunities to improve access in low- and middle-income countries (LMICs), where the need is greatest and where people face the greatest threat from superbug infections.

While the antibacterial and antifungal R&D pipeline remains small compared to the scale of the AMR threat, there is a slight increase in projects from the companies evaluated, and there are more projects that target pathogens in the highest risk categories defined by WHO and the US Centers for Disease Control (CDC). This includes Pfizer’s newly acquired antifungal candidate fosmanogepix, which targets pathogens including C. auris and potentially represents the first in a new class of antifungals. It also includes GSK’s gepotidacin, now in Phase III and the only medicine candidate analysed that is being tested against N. gonorrhoeae.

Almost a third of R&D projects target drug-resistant M. tuberculosis, which causes the bulk of drug-resistant infections globally. A further third target Gram-negative bacteria, mainly Enterobacteriaceae. This includes Johnson & Johnson’s E. coli vaccine (ExPEC9V), which if successful could prove an important tool for preventing invasive extraintestinal pathogenic E. coli disease.

Plans to address the access to and stewardship of new products in countries with high disease burdens have become common, now covering 18 of the 20 medicine candidates in Phase II or beyond. This is a significant improvement since the first Benchmark analysis, published in 2018, when only a handful of projects were covered by plans. Four companies now report policies for access and/or stewardship planning across their whole portfolios. Plans are expanding and becoming more detailed, although quality assessments will be required as projects progress and new products are launched.

Companies are doing more to limit the impact of antibacterial manufacturing on drug resistance, including by enforcing good practice with upstream partners. Abbott, for example, has introduced a new template contract for suppliers that specifically require them to meet AMR-related standards. Pharmaceutical companies rely on a large cohort of third-party suppliers for their antibacterial ingredients.

The baseline measure, as reported by the companies they supply, is that only 5.2% of third-party sites can be said to be compliant with set limits. Nine companies in scope are actively monitoring levels at own sites, as well as requesting and reviewing per-site discharge levels from third-party suppliers. Shionogi sets the standard for transparency, by publishing detailed information on compliance with set limits at each site. No company has yet insisted that external waste-treatment plants also meet environmental standards relating to AMR.

Companies are improving the availability of products by registering them for sale more widely in LMICs. Viatris, for example, has filed its multi-drug-resistant tuberculosis medicine pretomanid (Dovprela) in an additional 23 LMICs since 2020. Nevertheless, the number of filings per country remains low, and this low performance is mirrored in companies’ limited use of strategies to improve access to specific products. 

Only one third of the 166 products assessed are covered by any access strategy in any of the 102 countries assessed. Most products targeted by these strategies are either vaccines, anti-tuberculosis medicines or some of the antibiotics that WHO deems a priority for greater access. As in 2020, pharmaceutical companies are missing many opportunities to make antibiotics available in LMICs. 

There are, however, a handful of encouraging examples of industry action that show the direction for improvement. For example, almost all companies take steps to ensure an uninterrupted supply of antibiotics, such as implementing standardised forecasting processes, sharing demand data with stakeholders on a regular basis and establishing global supply networks. Further, ten companies are carrying out technology transfers as a means of boosting supply, including in five countries in Africa: Burkina Faso, Morocco, Nigeria, South Africa and Zambia.

Companies continue to improve stewardship efforts to safeguard the effectiveness of antimicrobial medicines, including how they tackle the risk of overselling. Once again, several companies, including three generic medicine manufacturers, have newly developed or strengthened policies in this area. Aurobindo, Shionogi and Teva go furthest, either by not promoting their products or by fully decoupling bonuses from sales volumes. One company, Cipla, has marginally weakened its policy on sales incentives, although it still goes further than other companies. Progress is clearer in other areas of stewardship, such as in monitoring the spread of resistance. 

Companies’ surveillance programmes cover a slightly broader range of pathogens on average than previously. Data-sharing has also increased, although there is still only one company, Pfizer, that makes its raw data public. This is despite long-standing commitments from others to take the same step. Actions to mitigate conflicts of interest in educational programmes for healthcare professionals have become standard. This is a big change since 2018, when lines between marketing and educational activities appeared blurred.

*Lists of pathogens identified as R&D priorities due to the threat from AMR have been published by WHO and the US Centers for Disease Control and Prevention (CDC). Both lists use multiple categories to designate risk levels. The highest levels are ‘critical’ (WHO) and ‘urgent’ (CDC).

** R&D projects active between 22 June 2019 and 30 April 2021, from the eight large research-based pharmaceutical companies in scope. By volume and value of sales, these are the largest players in the global antibiotics market that are active in innovative R&D today.