Signs of movement in access and stewardship planning in R&D, from a low base
Pharma companies have plans for access and stewardship for 8 out of 32 key candidate antibiotics (25%), up from 2 of 28 (7%) in 2018.
- Planning ahead while R&D projects are in clinical development accelerates access and stewardship for successful candidates.
- Clinical pipeline of antibiotics for priority infections remains small.
- With a small pipeline, the need for access and stewardship plans is more acute.
When the right antibiotics are unavailable, doctors often resort to suboptimal treatments, which gives pathogens an opportunity to develop resistance. By planning ahead – i.e., while a product is in clinical development – pharmaceutical companies can provide swifter access to new products at affordable prices, and have measures in place from day one to ensure new products are used prudently (known as stewardship).
Advance planning has been shown to improve the speed at which new medicines are made accessible. For example, Tetraphase worked with Everest, a China-based biopharmaceutical company, to register its new antibacterial eravacycline in China, receiving approval within one year of gaining market approval in the US. Eravacycline targets several drug-resistant infections.
It is well known that there are not enough antibiotics in R&D pipelines to replace those losing their effectiveness. With such small pipelines and such need, it is even more important for pharmaceutical companies to start putting access and stewardship plans in place during clinical development. The Benchmark considers that companies should know enough about a product’s prospects to start planning for access and stewardship from Phase II of clinical development.
What did the Benchmark analysis find?
The 2020 Antimicrobial Resistance Benchmark identified 32 priority candidate antibiotics from the companies in scope at the stage where access and stewardship planning should be taking place. Eight of these 32 antibiotics (25%) are supported by both access and stewardship plans. This is a notable, increase compared to 2018, when two out of 28 (7%) antibiotic candidates had both plans in place.
Advance planning is so far benefiting only a few diseases caused by a few pathogens. Out of the eight projects, two are for tuberculosis, two are for gonorrhoea and one is a broad-spectrum antibacterial for multi-drug resistant infections.
Johnson & Johnson’s paediatric bedaquiline formulation was one of only two projects recorded in 2018 as having both an access and a stewardship programme in place during clinical development. This project is still in phase II. The second project credited in 2018 was Tetraphase’s eravacyline. Since the 2018 Benchmark, eravacline was approved and Tetraphase signed its planned licensing agreement covering Southeast Asian countries, including Malaysia and Thailand.
Late-stage antibacterial candidates supported by access and stewardship plans:
- Sulbactam/durlobactam (Entasis), a beta-lactam/beta-lactamase inhibitor (BL/BLI) combination where sulbactam is active against A. baumannii and durlobactam confers additional protection against betalactamases.
- Zoliflodacin (Entasis), a novel candidate for the treatment of uncomplicated gonorrhoea, developed in partnership with the Global Antibiotic Research & Development Partnership (GARDP)
- GSK-070 (GSK) a novel candidate for the treatment of M. tuberculosis
- Gepotidacin (GSK), a novel candidate for the treatment of bacterial infections including N. gonorrhoeae
- Bedaquiline (Sirturo®) (Johnson & Johnson) paediatric studies, for the treatment of drug resistant tuberculosis in adolescents
- Aztreonam/avibactam (Pfizer), for the treatment of multi-drug resistant Enterobacteriaceae
- Ceftaroline fosamil (Zinforo) (Pfizer), for MRSA as a new target indication to an expanded paediatric population
- Eravacycline (Xerava) (Tetraphase), targeting multidrug-resistant Gram-negative and Gram-positive infections
What do access and stewardship plans look like?
There are various mechanisms that can enhance access to new medicines in low- and middle-income countries. These include licensing and affordability commitments, filing for registration in countries with a high disease burden, taking account of populations’ varying ability to pay in pricing strategies, and waiving or not enforcing patent rights. Stewardship measures can include surveillance of resistance and disease, and the introduction of more appropriate marketing practices. This is particularly important in countries with high rates of drug resistance. In some cases, product development partners require such plans to be made during the development phase. This is the case for six of the eight projects supported by both access and stewardship plans in 2020.
With only a few antibiotics in development, and considering the scale of unmet need, each new antibiotic must be protected at launch by access and stewardship plans. The practice of access and stewardship planning during clinical development needs to be significantly scaled up, particularly as the 13 candidates currently without such plans include new antibiotics critically needed to combat superbugs such as C. difficile, N. gonorrhoeae and MRSA. R&D funders can play a role by including provisions for and supporting access and stewardship planning during the later stages of development, when prospects for marketing approval are becoming clear.
Breakdown of the clinical antibiotic pipeline for priority bacteria and fungi