The diminishing arsenal of efficient antibiotics to fight bacteria is a threat denounced by many, but investment in research and development of new antibiotics is seen as lagging. As the danger of getting back to a pre-antibiotic age is increasing, alternative ways of financing new antibiotics are being discussed. At the World Investment Forum this week, a panel looked into innovative means of investment, and ways to attract private investors to this field.

The World Investment Forum of the United Nations Conference on Trade and Development (UNCTAD) is taking place from 22-26 October.

The panel “Fostering Investment in the Development of New Antibacterial Treatments” yesterday, co-organised by UNCTAD and the World Health Organization, explored potential solutions to attract new investors in the area of antimicrobial resistance. The organisers were also hoping that investors would get inspired by the panel’s discussions.

One of the key issues of antimicrobial resistance is the fact that new antimicrobials need to be used with scarcity, since the overuse of antibiotics leads to resistance. This restriction offers a bleak perspective for returns on the substantial investments needed to produce and commercialise new antibiotics. The private sector has thus not been eager to launch into costly research in this area, and public funding proves insufficient, according to participants.

CARB-X: Rigorous Review and Support

Richard Lawson, director of Portfolio support at CARB-X, a non-profit public-private partnership dedicated to accelerating antibacterial research, said CARB-X does not invest in basic research but rather in therapeutics, diagnostics, and vaccines in the early stages of research and development product development.

CARB-X orients its investment strategy toward priority pathogens on the WHO list, and the list of priority pathogens published by the United States Centers for Disease Control and Prevention, he said.

CARB-X invests funds provided by the US government, Wellcome Trust, NIAID, the UK government, the Bill & Melinda Gates Foundation, and the German government, as recently announced by the German Minister of Education and Research at the Grand Challenges meeting in Berlin.

Good investment goes through a rigorous scientific and business review process for each grant applicant, Lawson said. This assessment is carried out by scientific experts from around the world, consultants and advisors from industry and academia. It is a strict assessment from a scientific point of view but also a business due diligence perspective.

CARB-X aims at “making its investments even better” by forming a support team assembled through CARB-X network of accelerator partners to work with the companies which received grants through the length of time of the investment. Monthly meetings are organised with the company, with advice from scientific and business advisors, tailored to the needs of each company.

So far CARB-X has funded more than 30 projects, and is expected to grow that number to 40 by early next year.

CARB-X is also committed to access and conservation. One of its motto is “innovation without access is unjust, and without conservation it’s wasteful.”

AMR: Cannot Think “US FDA” Regulations, Producer Says

Anand Anandkumar, CEO of Bugworks Research, said antimicrobial resistance is not only an issue for developing countries but also for high-income countries. He mentioned a study by Public Health England, cited by CNN, stating that “antibiotic-resistant blood stream infections rose by 35% between 2013 and 2017 in England.”

“Antibiotics is the very edifice on which the entire modern medicine was built,” Anandkumar said. That building is at risk of crumbling, he said, adding that India is paying a large tribute to antimicrobial resistance, in particular in neonatal sepsis.

There was no new innovation in antibiotics “for many decades,” with the last new broad spectrum antibiotics dating back to the 1960s, he said. There were no new investments because large pharmaceutical companies went on to better areas in terms of business, such as cancer, he added.

It is a perfect storm, he said, asking, who wants to invest a billion dollars in a drug and then be told “don’t use it.” At the same time, it is a great opportunity, in particular by walking away from volume dynamics, he said.

Bugworks has been around for five years and hosts 20 people in India, he said, with funding from CARB-X. Over one billion dollars has been invested in the last two years thanks in particular to CARB-X, the Wellcome Trust, and the Global Antibiotic Research & Development Partnership (GARDP), to promote early stage drug discovery, Anandkumar said.

For companies like Bugworks, he said some 70 percent of the cost from innovation to market could be shouldered by global grants, and hopefully the 30 percent left will be financed by private ventures.

AMR has to be considered on its own by regulatory authorities, he said, “we cannot afford to think US FDA [Food and Drug Administration],” adding that regulatory authorities have to rely on clinical trials coming from countries having the largest burden of diseases. It takes up to five years to recruit patients for clinical trials for a new drug in the US, he said, “I can get that done in four to six months.”

“We cannot afford to think the western market style,” he said. AMR is a space dominated by small and medium-sized companies, and how they conduct clinical trials, how they collaborate, is very different from how big pharmaceutical companies look at it. He underlined a lack of business capacity as a “huge challenge” and the lack of pull incentives.

Some are considering market entry rewards as a solution to stimulate innovation, like US$1billion for each new product, he said. So US$20 billion would be enough to bring 20 new antibiotics to the market, he said. “It is doable, market entry will happen,” he added.

A report [pdf] by the Driving reinvestment in research and development and responsible antibiotic use (Drive-AB), a project composed of 15 public and 7 private partners from 12 countries, and funded by the Innovative Medicines Initiative (IMI), a joint undertaking between the European Union and the European Pharmaceutical Industry Association suggested that US$1 billion market entry reward per antibiotic globally could quadruple the number of new antibiotics coming to the market in the next 30 years.

Sweden Pilot Project For Availability of Antibiotics

Jenny Hellman, of the Public Health Agency of Sweden presented the Swedish model to keep antibiotics on the market. This model is partly delinking volume and sales, she said.

According to Hellman, in Sweden there is a low resistance rate but the number of antibiotic-resistant infections in increasing. Antibiotics are being used very restrictively in Sweden, she said, and considering the size of the country, it is a small market. Some products face such low demand that there is a risk that they might not be available from pharmaceutical companies.

The Public Health Agency was tasked in 2017 by the Swedish government, through a commission, to propose models to remedy the potential threat of the unavailability of some antibiotics, she said.

In 2018, a new commission was set up, to report back in 2022. The commission is expected to run a pilot of the suggested delinked model for two new antibiotics with market protection.

The commission identified solutions for different categories of antibiotics, she said. First antibiotics with law sales are identified, then they are evaluated for their activity against identified high-risk resistance types, in order to define their specific medical value, she said.

The proposed economic model for new antibiotics with market protection, low-expected sales and special medical value, is to guarantee a minimum annual revenue for the pharmaceutical companies. In return, the companies would deliver a certain amount of products. Discussions with pharmaceutical companies have not started, she said.

The size of the guaranteed compensation would be based on the estimation of the volume of products necessary to be available in Sweden, she added.

GARDP: Looking at Innovation but also at Old Antibiotics

Jean-Pierre Paccaud, GARDP Incubation Business Development & Strategy Director, Drugs for Neglected Diseases initiatives (DNDi), said the debate on AMR and drug development need to be reframed, and focus should be on the incentivised approaches that cover all the activities around AMR.

“We need to act from end to end, not only to encourage early stage discovery, but thinking past the registration, distribution, stewardship, and sustainable access, as key features,” to be successful.

GARDP proposes to look at public health priorities as a driving force, to think outside the box by looking at needed innovations but also considering old antibiotics, he said.

He said GARDP has “a sweet spot” for middle-income countries in terms of addressing their needs, and will make sure that any tool GARDP develops will be brought to emerging economies.

At the moment, GARDP is working on selected indications: neonatal sepsis, sexually transmitted infection and in particular gonorrhoea, and antibiotics formulation for children, Paccaud said. GARDP is also looking at recovering and recouping the investments and energy deployed in the past by scientists in the field of antibiotics, by reaching out to them and share their knowledge with the community, he said. GARDP is considering extending its indications in the future, he added.