Current investments are not enough, need to be supplemented
Globally, discussions on the need for an antibiotic development pipeline have been gaining momentum. There is an emerging consensus that novel financing models must come up to rejuvenate the dipping pipeline, which has often been attributed to a broken market for antibiotics.
An ongoing incentive model is the ‘push’ incentive, which aims to push the antibiotic candidate under development through different stages of basic research, preclinical and clinical trials.
Push incentive, therefore, involves funding mostly the early stages of antibiotic development carried out by small and medium size developers through the involvement of philanthropic organisations, public-private partnerships, industry and the governments.
They help reduce development costs and the risk of failure is also shared by the funder.
There are different push incentives currently in operation. For example, Combating Antibiotic-Resistant Bacteria Biopharmaceutical Accelerator (CARB-X) and the United Kingdom government’s Global Antimicrobial Resistance Innovation Fund (GAMRIF) focus on discovery and early-stage funding.
Those like Global Antibiotic Research and Development Partnership (GARD-P) and AMR Action Fund support the late-stage development. The United States government’s Biomedical Advanced Research and Development Authority (BARDA) helps with end-to-end product development, while the Joint Programming Initiative on AMR (JPIAMR) is looking at basic exploratory research.
The development of various products is currently supported by these push incentives. CARB-X is currently supporting 30 projects that include therapeutics (for example, antibiotics), preventatives (for example, vaccines) and diagnostics.
BARDA supports CARB-X and recently committed an additional $370 million along with London-based charitable foundation Wellcome Trust. GARDP, which is developing five antibiotics by 2025 under its 5 BY 25 initiative, has invested around EUR 28 million for development of antibiotics against sepsis for children.
The UK government has invested GBP 20 million for three years in CARB-X and GBP 4.5 million for four years in GARDP through GAMRIF. Industry initiatives like the AMR Action Fund, which has commitment of $1 billion over 10 years shared by 20 companies, is currently supporting five developers.
Push incentives, however, have their own set of challenges. In a recent webinar organised by the Delhi-based thinktank Centre for Science and Environment to discuss the antibiotic research and development crisis, Richard Lawson, Senior Project Manager, CARBX acknowledged that these incentives alone cannot do the job.
Speaking about the small and medium antibiotic developers, he said, “One of the greatest risks that we have is that CARBX and other organisations will advance these projects to a cliff, where there is nowhere else for them to go. There is no downstream funding to work towards”.
The webinar was based on CSE’s latest assessment — A Developing Crisis — which talked about the fragile and thin global antibiotic pipeline, the exit of major pharmaceutical players from antibiotic R&D space, and what needs to be done further.
The webinar brought together key stakeholders and experts like Lawson, James Anderson, executive director, global health, International Federation of Pharmaceutical Manufacturers and Associations (IFPMA), and Lesley Ogilvie, director of the secretariat, Global AMR R&D Hub.
“Small- and medium-scale antibiotic developers may also not have access to or be able to afford all the skills, capabilities or expertise that are needed,” said Lawson.
“CARBX not only helps companies advance their product and also prepares them for the next step, which includes where the next stage of funding is going to come from and how we can make that case for the next stage.”
Echoing the same, Daminao De Felice, Director of Development and External Engagement at CARBX acknowledges that the teams that bring these innovations are often very small and typically expert with the foundational technologies but not with drug discovery and development.
“Additionally, because of the high level of innovation of many programs that CARB-X supports, there is little to no precedence with many pre-clinical models, particularly animal models of infection, as well as clinical development and regulatory strategies,” he said.
With GARDP, which looks at late stage antibiotic, the limitations are different. Manica Balasegaram, Executive Director of the GARDP highlights that antibiotic development becomes more challenging when clinical trials are needed to be conducted in diverse geographies and populations.
Another issue is that of ensuring access to the new antibiotics it is developing in partnership with companies as well as existing antibiotics, even if it did not play a role in the development of the antibiotic.
“Sustainable access to antibiotics is highly challenging — whether due to a lack of laboratory and diagnostic capacity, insufficient capacity or resources in the health system, and challenges with forecasting demand to ensure adequate quantities of an antibiotic are available when required,” said Balasegaram.
Developing new antibiotics for children and newborns is also another important area that needs attention since their bodies react differently than adult bodies.
GARDP is addressing these challenges by forming collaborations and networks, enabling better access in low- or middle-income countries through its SECURE initiative,and identifying and developing new treatments for children and newborns.
The webinar acknowledged that, besides funding, appropriate implementation mechanisms for current incentives are needed to ensure a robust and sustainable innovation ecosystem. “We need to build more robustness and resilience in funding for the antibiotic development pipeline,” said Ogilvie at the webinar.
Experts also emphasised the importance of coordination, collaboration and communication as the keys, in addition to money.
Lawson, highlighted how Bugworks Research Inc., which was initially supported by CARB-X since 2017, from lead optimisation to phase-I clinical trials, was now joining hands with GARDP to forward the development of a novel antibiotic, BWC0977.
The potential antibiotic will help treat serious bacterial infections in both critical care and community settings, as well as infections caused by drug resistant pathogens in hospital settings.
“Vast parts of the world need access to antimicrobials, and they need to get this at affordable costs. The development of new antimicrobials has therefore to be linked with the issue of affordability and access,” said Sunita Narain, director general, CSE, who moderated the recently concluded webinar.
Push incentives, like GARDP and CARBX are also taking into consideration the importance of ensuring access as well as stewardship while working with developers.
Push incentives are working. There have been examples of some successes, but the current investments are not enough and need to be supplemented.
“More push funding is definitely needed for early stage and preclinical research,” said Christine Ardal from the Norwegian Institute of Public Health.
“While CARB-X and GARDP are doing fantastic jobs supporting the current pipeline, they would both benefit from additional financing. They are unable to support all promising antibacterial candidates. Especially, if we seek truly innovative candidates that will have a higher failure rate, we need more investment in push funding,” said Ardal.
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