November 21, 2022
A major change has been underway over the past decade, making certain medicines more accessible for people who need them most. Drug development companies have become increasingly open to voluntary license agreements—that is, agreements that make it possible to manufacture and commercialize select medicines for critical public health needs, especially in low-income countries. The launch of the Medicines Patent Pool (MPP) significantly accelerated voluntary licensing and improved access conditions, for example by expanding the geographic scope of many licenses and requiring quality assurance for licensed products. Either bilaterally or through the MPP, voluntary license agreements have been signed for medicines to treat HIV, tuberculosis and COVID-19. However, apart from medicines for tuberculosis, such an agreement has never been signed for an antibiotic—until now.
On 15 June 2022, Shionogi & Co., Ltd. (Shionogi) and the Global Antibiotic Research and Development Partnership (legally “GARDP Foundation”, or GARDP) signed a license and technology transfer agreement to accelerate access to cefiderocol, an antibiotic for the treatment in adults of certain serious bacterial infections, which may be resistant to other antibiotic treatments. Cefiderocol is approved by the U.S. Food and Drug Administration and the European Medicines Agency and is on the World Health Organization (WHO) Essential Medicines List. To facilitate the manufacture, commercialization and appropriate use of cefiderocol in the licensed territory, Shionogi, GARDP and the Clinton Health Access Initiative (CHAI) signed a collaboration agreement under which CHAI is primarily responsible for the selection process for a suitable manufacturer and will contribute to all other workstreams.
Together, these agreements have the potential to make cefiderocol accessible in a large range of countries that tend to have delayed access (if any) to newer antibiotics. The license territory includes the public and private sectors in all low-income countries, most lower middle- and upper middle-income countries, and select high-income countries. With 135 countries total—almost 70% of countries worldwide—the licensed territory includes a significant proportion of the world’s population living in areas most affected by antibiotic resistance (see License Agreement Overview and recent study of global burden of antibiotic resistance).
The collaboration between GARDP, Shionogi, and CHAI represents a breakthrough in using voluntary licensing to enable access to newer antibiotics. In particular, the license agreement creates a new paradigm for licensing important medications beyond HIV, malaria and tuberculosis, which have been the primary focus of global health efforts. The license agreement also holds strategic significance as the first of its kind for an antibiotic driven by public health priorities. It is also significant that the license has been provided by one of the few mid- or large-sized pharmaceutical companies with an active antibiotic development portfolio.
There are three other noteworthy aspects of the collaboration: technology transfer, affordability, and appropriate use. If a manufacturer requests a technology transfer, Shionogi will provide one technology transfer of its manufacturing process, including relevant know-how, to one manufacturing sub-licensee. Alternatively, if the manufacturers of the active pharmaceutical ingredient (API) for cefiderocol and the finished pharmaceutical product are different, then Shionogi will provide partial technology transfers to each manufacturer which, in combination, cover the development from API to finished pharmaceutical product. Shionogi will also provide access to documents and necessary rights to facilitate registration with regulatory bodies.
In an effort to support affordable access, Shionogi has waved its cost recoupment fees on net sales of cefiderocol in low-income and lower middle-income countries within the licensed territory. Shionogi is entitled to 5% and 9% recoupment fees on net sales in upper middle-income and high-income countries within the licensed territory, respectively. These terms compare favourably to cost-recoupment rates in other recent published licenses for territories that include upper middle-income countries or high-income countries.
Production of quality-assured products and the appropriate use of antibiotics are essential to any effort to expand antibiotic access. Falsified or poor quality antibiotics, as well as antibiotic overuse and misuse may fuel antibiotic resistance. Accordingly, the license agreement requires that the licensed product be manufactured by a sub-licensee that is demonstrably quality-assured through approval by the WHO Prequalification Programme or a stringent regulatory authority (e.g. a WHO-listed regulatory authority). Moreover, sub-licensee agreements and the sublicense access plan (to be developed with sub-licensees) will have stewardship clauses that require appropriate use and that complement additional stewardship activities/partnerships.
To facilitate future voluntary licencing agreements for antibiotics, Shionogi and GARDP have published the full content of the license and technology transfer agreement. It details who will own intellectual property resulting from the agreement, for both the manufacturing process and development activities. The hope is that this license agreement may serve as a baseline for similar agreements that expand access to antibiotics in the future.
Jennifer Cohn, MD, MPH, is the Director of Global Access at GARDP. Gareth Morgan is the Head of Global Portfolio Management at Shionogi Inc. David Ripin, PhD, is the Executive Vice President of Infectious Diseases and the Chief Science Officer at CHAI.
Please refer to the U.S. Prescribing Information for cefiderocol.