In R&D, increased access and stewardship planning for medicines and vaccines

• Almost all of the medicine candidates that have reached Phase II or beyond are now supported by both stewardship and access plans

• There remain big differences in companies’ approaches to access and stewardship

By planning ahead while a product is still 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 appropriately (known as stewardship). 

Phase II of clinical development is widely agreed by stakeholders as the point where such planning should start. Looking at the pipelines of the eight companies in scope, almost all of the medicine candidates that have reached Phase II or beyond are now supported by both stewardship and access plans. 

This is a significant improvement since the publication of the 2018 AMR Benchmark, when only a handful of candidates were supported. The companies’ vaccine projects are now also all covered by access plans (stewardship is not a primary concern for vaccines).

Overall, 18 out of the 20 late-stage medicine projects in this analysis have both access and stewardship plans in place, confirming a trend suggested in the 2020 Benchmark, when the number of projects with both access and stewardship plans rose from two to four. 

All 11 late-stage vaccine projects have access plans in 2021, a further improvement since 2020, when eight of 12 vaccines had access plans. There remain big differences in companies’ approaches to access and stewardship and how comprehensive their plans are. 

The best examples identified by the Benchmark now include a more comprehensive range of access and stewardship measures. 

However, some companies have added more breadth to their portfolio-wide policies on access and stewardship planning since the previous Benchmark. Most companies report project-specific access and stewardship plans for at least some of their projects in late-stage development.

The best examples identified by the Benchmark now include a more comprehensive range of access and stewardship measures. 

Companies are making use of strategies such as affordability frameworks, technology transfers to generic medicine manufacturers, WHO prequalification applications, compassionate use programmes, and the expansion of registration filings, as well as implementing other access provisions stipulated in contractual agreements with funders and partners (e.g., the Global Drug Facility, the Bill & Melinda Gates Foundation, Wellcome Trust, and Gavi, The Vaccine Alliance). 

Projects funded by organisations, such as the Bill & Melinda Gates Foundation and Wellcome Trust, that request access provisions in their contracts, tend to have stronger, multifaceted access plans. 

A working group of experts, led by Wellcome Trust and including the Access to Medicine Foundation, have released a Stewardship and Access Plan (SAP) Development Guide that sets out practical actions that pharma companies and product developers can take to develop robust plans early on. 

The Combating Antibiotic-Resistant Bacteria Biopharmaceutical Accelerator (CARB-X) now requires that all grant recipients commit to creating a SAP within 90 days of their product entering pivotal clinical trials (Phase III). Further, grantees are expected to develop a strategy to monitor the effectiveness of such plans.

Among the medicine projects with the most robust plans are Otsuka’s OPC167832 and its paediatric adaptation of the anti-tuberculosis medicine delamanid (Deltyba). 

For the latter, Otsuka is building on its experience gained when bringing the adult version of delamanid to market and is taking steps to make the paediatric version rapidly available and suitably formulated for children. 

A 25mg paediatric dose of delamanid for children has received approval from the European Medicines Agency (EMA). The company is partnering with the Global Drug Facility, generic medicine manufacturers, and children-oriented organisations to develop routes for access, and is donating its product to research institutions to build on its applications. 

Otsuka’s OPC-167832 is also supported by robust access provisions, stipulated through a contractual agreement with the Bill & Melinda Gates Foundation, which co-funds the development of this Phase II anti-tuberculosis candidate.

Depth and specificity

Also strongly supported by access and stewardship provisions is Pfizer’s aztreonam+avibactam. Pfizer has eight late-stage R&D projects targeting pathogens in scope, four medicines and four vaccines, the most of any company evaluated. 

Pfizer has added depth and specificity to its access and stewardship plans since 2020, which now include a wide range of strategies to ensure access in low and middle-income countries (LMICs). 

Pfizer implemented a new policy that went into effect in May 2020 stating that it will not enforce its patents in least developed countries (LDCs). Furthermore, its late-stage R&D medicine projects fall under portfolio-wide stewardship plans, including initiatives for surveillance and research and education on AMR (via unrestricted grants). 

For its recently acquired Phase II antifungal, fosmanogepix, Pfizer plans to continue the Expanded Access Programme that Amplyx Pharmaceuticals Inc. had started.

Pfizer’s four vaccines are also among the better covered in terms of access plans of the 11 vaccines in late-stage development included in this analysis. These include Pfizer’s new pneumococcal 20-valent conjugate vaccine, Prevnar20™ (recently approved for adults), and its vaccines targeting C. difficile and Group B Streptococcus. The latter is being co-funded by the Bill & Melinda Gates Foundation. 

Approved in India in May 2021, Sanofi’s Shan6™ vaccine was specifically developed for children in low- and middle- income countries. This vaccine targets six pathogens, adding polio to the group of pathogens previously targeted by the company’s Shan5™ vaccine. Sanofi has a dedicated manufacturing facility in India, where it applies supply-chain best practices including buffer and safety stocks.

Additional countries in scope for registration include Thailand and Kenya, where there are ongoing Phase III trials. For Shan6™, Sanofi has applied for WHO prequalification to ensure access to the vaccine in all countries eligible for support from Gavi, The Vaccine Alliance.

Pooled procurement, for example via Gavi and UNICEF, is an effective route to ensure quality, supported by WHO’s Prequalification process, and to enable countries to access a stable and affordable supply of vaccines. 

In addition, Sanofi has developed equitable pricing strategies, conducted a payer pricing survey in nine countries, and takes account of affordability by market type.

Companies use varied approaches

With strong company-wide policies for access and stewardship, GSK has five late-stage R&D projects targeting pathogens in scope, and reports having project-specific access plans for most of them. 

All five projects have ongoing trials in LMICs. GSK does not conduct clinical trials in countries where it does not intend to pursue registration and to make the product available for use. GSK reports that it has developed an equitable pricing strategy framework for LMICs that applies across its portfolio and business units. 

Its access plans include equitable pricing strategies, registration filings, non-exclusive licensing and supply chain commitments. GSK states that it does not file patents in LDCs or low-income countries nor does it enforce historic patents. GSK commits to conducting global surveillance studies for its new antibacterials to enable appropriate use and support stewardship.

Johnson & Johnson has one vaccine (ExPEC9V) and one medicine in late-stage development, the paediatric adaptation of the anti-tuberculosis medicine bedaquiline (Sirturo). 

They are both covered by project-specific access plans. The current stewardship activities ongoing for the adult indication of bedaquiline (Sirturo) will extend to the newly approved paediatric indication, for use in patients aged 5-12 years and weighing at least 15 kg. 

There are no clinical trials running for the EXPEC9V vaccine in any of the 102 LMICs examined for this analysis, but Johnson & Johnson is planning to expand its Phase III trial to include LMICs.

Shionogi has progressed in this area by actively seeking out partners to improve access to, and stewardship of, its recently approved antibiotic cefiderocol (Fetroja/Fetcroja). 

MSD does report a general commitment to improving access, through registration and affordability measures, and to ensuring stewardship, primarily through surveillance. Novartis does not have any R&D projects that are eligible for this assessment.