In the five years since the Access to Medicines Foundation released its last antimicrobial resistance benchmark, the pipeline for new projects in development has shrunk by a not inconsiderable 35% within large research-based companies, reports Devex.
In a new benchmark, the foundation continues to track the actions pharmaceutical companies are taking to combat the rise of antimicrobial resistance, or AMR, including the development of new products, but the data in the new report, said Jayasree Iyer, the foundation’s CEO, “tell a sobering story”, including a shrinking pipeline for both adult and paediatric products.
While smaller biotech companies are attempting to enter the space, they lack the resources and reach to meet the challenge.
“We do not have enough research going into the antimicrobial space to outpace resistance,” said Claudia Martinez, director of research at the foundation, during a press conference to launch the new benchmark.
Why it matters
At least 1m people die every year directly from drug-resistant infections, and another 5m deaths are indirectly linked to AMR, according to the World Health Organisation.
As resistance increases, those numbers will continue to rise unless new products are developed. It’s a problem then, that only three large research-based companies – GSK, Otsuka, and Shionogi – are actively developing antimicrobials innovative enough to reduce the risk of rapid resistance.
This is the result, in part, of a market failure, said John-Arne Røttingen, the CEO at Wellcome, during the press conference. Prescribers tend to prioritise treating patients with established, generic medications.
That’s because they are more affordable than new drugs.
The practice also holds new innovations in reserve to reduce the risk of resistance emerging, so they will actually work in the cases when they are needed. But it creates a challenge for the innovator.
“The revenue that you can get from an antibiotic in the lifetime of the patent protection is relatively small compared with any other therapy area,” he said. That means there is a need to create incentives, like lump sum payments when a new drug hits the market, to encourage research and development.
At the same time, when new products are developed, there are crucial gaps in getting those treatments to low- and middle-income countries, according to the benchmark. Of the products they considered, companies only had access strategies in place for 44%.
This includes steps like voluntary licensing, pooled procurement mechanisms, or pricing strategies to make the new products available in lower-income settings.
Even getting drugs that are no longer patented to LMICs remains a challenge, according to the benchmark.
Since 2021, there has been no significant increase in the number of product registrations in LMICs, which can lead to treatment gaps.
The report particularly highlights a stark lack of antibiotics formulated for children. Only 14% of medicines under development by the companies assessed are for those aged under five.
In Sub-Saharan Africa, 17 countries have no children’s antibiotics available from these companies.
In the pipeline
While big pharma companies like GSK are slated to put a few new drugs on the market in the coming years, their accessibility and affordability in LMICs might not be far-reaching, the report suggests.
Seven drugs in late-stage development promise to treat infections that have demonstrated resistance to other existing antibiotics – from gonorrhoea to urinary tract infections (UTIs) to drug-resistance TB, according to the report, which looked at 25 companies.
UK-based GSK is involved in three of them, including the already-approved UTI antibiotic gepotidacin, while other drugs will come from smaller companies like Venatorx and Innoviva.
All companies involved in the development of new antimicrobials have plans to get their drugs registered, to implement early-access programmes, and to ensure that patients involved in clinical trials can access the medicines after the studies end, the report says.
But of these seven upcoming antimicrobials, only two, from Innoviva and Otsuka, are expected to be available at an affordable price in low- and middle-income countries.
“With these treatments so close to reaching the market, the current gaps in access planning could leave millions in LMICs with delayed treatment, or no access at all,” the report says.
Incentivising innovation
Martijn van Gerven, research programme manager for the Access to Medicine Foundation’s AMR programme, told SciDev.Net that companies need to have external incentives to make their medicines widely available, such as governments promoting research and development or revenue-guarantee schemes, like those implemented in the UK.
Antibiotics are expensive to make and are not used continuously, making them an unattractive investment for many companies, Van Gerven said.
The subscription model works when governments pay a subscription to drugs, to ensure that they remain available regardless of market dynamics.
But this needs to be done on a global scale for it to be successful, Røttingen said.
And Martinez added that although most companies analysed in the report do have plans to make their products accessible, the problem is the lack of specificity of those plans.
“What we want to see is not a huge lag between registration and availability,” she said.
Most antibiotics sold worldwide come from generics manufacturers, and are mostly distributed in low- and middle-income countries.
The Benchmark report analysed 10 generics manufacturers, including Abbott, Hikma and Sandoz, and found that six of them tracked how many patients their products reach in LMICs.
Sandoz and Viatris were the only companies that did this kind of tracking for all their medicines. Fresenius Kabi and Alkem do not disclose details on their patient tracking methodologies, according to the report.
Local manufacturing
For Ayodele Majekodunmi, a Nigeria-based One Health epidemiologist and executive director of the data company Ajisefini Consulting, the real game-changer when it comes to reaching low- and middle-income countries is ensuring that at least part of the manufacturing takes place in those countries, allowing prices to drop.
This can be done when big pharma companies partner with and transfer knowledge to other companies in the global South, or when those big players set up factories in lower-income regions, said Majekodunmi, who is also project lead for the World Organisation for Animal Health’s Health Security Programme, West and Central Africa.
But the former leaves those countries less vulnerable to big pharma companies that may decide to leave a particular market, she added.
“Where you have local companies that are owned by people in that country, there’s nowhere for you to pack up and go. So local ownership and local investment is needed, definitely,” Majekodunmi told SciDev.Net.
Affordable access
Anand Anandkumar, founder of the India-based biopharmaceutical company Bugworks, said he is implementing a strategy to ensure his company’s novel antibiotics – which haven’t yet gone through human trials – reach as many people as possible around the globe once they are ready to be sold.
Bugworks is working with the Global Antibiotic Research and Development Partnership (GARDP) to make its products affordable, according to Anandkumar.
Subject to regulatory approvals, Anandkumar expects his antibiotics to be manufactured in India and for GARDP to help stockpile them for distribution in Latin America and Africa.
“I think if you give enough volume guarantees, manufacturers in India can manufacture a tonne of products for most of the developing world,” he said.
GSK’s chief scientific officer Tony Wood said GSK was using cutting-edge technology to bring much-needed innovation to patients, including a new first-in-class antibiotic last year.
“While this is welcome progress, it is not enough and today’s report underlines the need for governments and industry to work together to improve economic incentivisation of R&D and implement better access and stewardship models,” he said.
SciDev.Net Global article – Few new antibiotics for children, report warns (Open access)
Devex article – Will antimicrobial resistance outpace research? (Open access)
See more from MedicalBrief archives:
Mass treatment with antibiotic may increase AMR – London-Malawi study
AMR burden weighs heavily on Africa – global study
Agricultural antibiotics linked to Nigerian babies born with AMR
New antibiotics vital to combat AMR – WHO
AMR in Africa spikes with inappropriate antibiotic use