Japanese drugmaker Shionogi and the Global Antibiotic Research and Development Partnership (GARDP) announced today a first-of-its kind agreement to expand access to a novel antibiotic for drug-resistant infections in lower-resource countries.
Under the license and technology transfer agreement, GARDP will work with partners to manufacture and commercialize cefiderocol, developed by Shionogi, in up to 135 countries, many of them low- and middle-income countries (LMICs). Also involved in the agreement is the Clinton Health Access Initiative (CHAI), which will help navigate the technical, regulatory, legal, and economic hurdles to getting the antibiotic into these countries.
"Shionogi is proud to work on such an innovative license agreement with GARDP and CHAI to accelerate antibiotic access," Shionogi Director and Executive Vice President Takuko Sawada said in a joint press release. "Shionogi is committed to ensuring that cefiderocol is accessible worldwide as a potential treatment option for certain highly resistant Gram-negative infections."
Cefiderocol is a cephalosporin antibiotic with a novel method of penetrating the tough outer membrane of gram-negative bacteria, including strains that are resistant to several other antibiotics. Approved by the US Food and Drug Administration in 2019 and by the European Medicines Agency in 2020, it's considered an important antibiotic against multidrug-resistant (MDR) infections with limited or no other treatment options and is on the World Health Organization Model List of Essential Medicines.
But as is the case with many new antibiotics, cefiderocol is currently commercialized only in the United States and a handful of Western European countries. The licensing agreement aims to make it a treatment option for people in countries where antimicrobial resistance (AMR) is rising and antibiotic treatment options for infections caused by MDR bacteria are limited or nonexistent.
The GRAM report, published earlier this year, found that AMR caused 1.27 million deaths worldwide in 2019, and that LMICs in Africa and South Asia were among the most heavily affected by resistant infections.
A 'huge milestone'
While pharmaceutical companies have signed licensing agreements with nonprofits to increase access to drugs for public health priorities like HIV and malaria, this is the first such agreement for an antibiotic.
"This is one of the broadest public-health oriented, voluntary licensing agreements around, and it includes many of the countries with the highest burden of these very-resistant gram-negative strains," Jennifer Cohn, MD, GARDP's Global Access Project leader and an infectious disease physician at the University of Pennsylvania Perelman School of Medicine, told CIDRAP News.
The agreement builds on a partnership between Shionogi, GARDP, and CHAI that began in July 2021. Cohn says the aim of that partnership was to figure out what the three organizations could do to improve treatment options for antibiotic-resistant bacteria globally, particularly in countries with a high burden of infectious disease and limited access to newer antibiotics, and what role cefiderocol could play.
"This license and technology transfer agreement is really a huge milestone in that collaboration, but in a way it's only the beginning of the work that we're planning to do," Cohn said.
Under the agreement, Shionogi is granting GARDP the license for cefiderocol and will provide technology and "relevant know-how" for its manufacturing process to sub-licensees identified by GARDP. CHAI will provide guidance on how to reach patients in need and work with licensed manufacturers to produce an affordable product.
"CHAI is excited to be a part of this partnership that will ensure that this innovative antibiotic is affordable and available to patients when and where they need it," David Ripin, PhD, chief science officer and executive vice president of infectious diseases at CHAI, said in today's press release.
That next steps, Cohn explained, will include finding local partners to manufacture, commercialize, and distribute the drug; providing quality assurance; making sure cefiderocol is registered to be marketed and sold in these countries and that licensed rights are used to improve affordable and equitable access; and working with local health officials to identify where the drug is needed and to develop and update guidelines and training for responsible use.
Cohn said GARDP will aim to work with countries that have a high AMR burden and whose governments have made a political commitment—through implementation of a National Action Plan on AMR—to appropriate antibiotic use. GARDP will help those countries improve their surveillance to identify potential resistance to cefiderocol. In addition, stewardship clauses will be included in sub-licensee agreements.
"We want to work with partners on the ground to ensure that the product is used appropriately," she said.
Partnership could set precedent
The agreement could be a significant boost for efforts to address limited antibiotic access in many LMICs, an issue highlighted in a report last week from the Access to Medicine Foundation.
The report argued that, while much of the focus in discussions of AMR revolve around overuse of antibiotics, the weak antibiotic pipeline, and the broken financial market for new antibiotics, in many countries people cannot get the antibiotic they need to properly treat an infection. And that lack of access to the right antibiotic also promotes the development of antibiotic resistance.
Access to Medicine Foundation CEO Jayasree Iyer, PhD, said the partnership between GARDP, Shionogi, and CHAI—which was highlighted in the report—could set a precedent for improving access to innovative antibiotics in LMICs. That's because it shows smaller pharmaceutical and biotech companies, who are driving most new antibiotic development and may lack the resources to get their products into lower-resourced countries, that it is possible with the right partners.
"It's significant for a company that has little presence in low- and middle-income countries, like Shionogi, to enter into an arrangement like this," Iyer said. "Even if they don't have the presence and means to reach patients, by partnering with GARDP and CHAI, they enable access, which sets a good standard."
