LONDON – A €9.4 million (US$11.5 million) EU study investigating ways to invigorate antibiotic development recommends there should be a market entry award of $1 billion for companies that succeed in getting a novel product to market.

To qualify for an award, a product must meet a pre-defined target profile set by the World Health Organization and the company must agree to a stewardship program to avoid overuse that could prompt to the rapid development of bacterial resistance.

The final report of the project, Drive-AB (Driving reinvestment in R&D for antibiotics and advocating their responsible use) concluded that a $1 billion market entry award, given in annual installments of $200 million in the first five years after a product is approved, would significantly increase the number of new antibiotics coming to the market.

Rather than four antibiotics with distinct new mechanisms, as implied by current pipelines, there would be 16 to 20 "truly innovative" products over the next 30 years.

That is not a figure plucked from the air, but the finding of an extensive simulation based on a set of antibiotic-specific R&D and market parameters.

The $1 billion award would be in addition to sales of a product, a suggestion which some members of Drive-AB – involving 16 academic partners and seven pharma companies – argued would leave in place an incentive for manufacturers to oversell a product, promoting resistance. The consortium agreed that is a risk and said it must be monitored closely.

Drive-AB represents the most thorough piece of research to date into ways of fixing the economic model to incentivize companies to invest in development whilst promoting sustainable use of approved antibiotics.

Publication of Drive-AB's report coincided with the unveiling of the first independent comparison of pharma companies' current efforts to address antimicrobial resistance (AMR).

The benchmarking exercise, carried out by the Access to Medicine Foundation, concluded Glaxosmithkline plc and Johnson &Johnson Inc. lead the field in terms of investment in R&D and the size of their anti-infectives pipelines, and also in dismantling incentives for sales staff to oversell antibiotics.

There is a balancing act between making sure antibiotics are available when they are needed, particularly in developing countries, and ensuring they are not overused, said Jay Iyer, executive director of the Access to Medicine Foundation, launching the AMR Benchmark at the World Economic Forum in Davos, Switzerland, on Tuesday.

"It was a surprise to us; companies are taking action, for example changing the way they encourage sales, rewarding staff for their technical knowledge at a services level, so that antibiotics are not oversold," Iyer said.

The AMR Benchmarking study "highlights the challenges of developing these sorts of medicines," said Paul Stoffels, chief scientific officer of J&J, speaking at the launch in Davos.

As a specific example, Stoffels cited Sirturo (bedaquiline), J&J's treatment for multidrug-resistant tuberculosis. On its approval in 2012 – after eight years in development – it became the first new TB treatment in four decades.

But in order to preserve effectiveness, Sirturo has been strictly rationed to ensure only those whose infections will not respond to any other drugs get access.

The restrictions mean that to date only 40,000 patients have been treated with Sirturo. "It is absolutely not a viable business model," Stoffels said, adding, "But absolutely, from a human perspective, it was the right thing to do."

'A key turning point'

The Dutch and U.K. governments funded Amsterdam-based Access to Medicines to compile the AMR Benchmark. It parallels other indexes the foundation draws up to track the effort pharma companies put into ensuring their products are as widely available as possible.

The example of Sirturo underscores the need for new economic models such as those proposed by Drive-AB. The consortium, which was managed by the University of Geneva and Astrazeneca plc, assessed more than 30 incentive schemes in use in other industry sectors for how each would affect innovation, sustainable use and equitable access.

"Drive-AB's report is a key turning point in the global conversation about AMR," said John Rex, chief medical officer of the U.K. anti-infectives company F2G Ltd. and expert in residence at the medical research charity Wellcome Trust.

"[The report] provides global leaders with a vital roadmap for addressing the problem of AMR," Rex told BioWorld.

In addition to developing new economic models, Drive-AB has worked to define standards and metrics for tracking the responsible and appropriate use of antibiotics across different health care settings.

While market entry awards would represent a significant new approach to stimulating antibiotic innovation, traditional incentives, in the shape of nondilutive grant funding, also need to be boosted, Drive-AB said.

Currently, global public funding of antibiotic R&D stands at $550 million. That is too low, the report noted. "We estimate that $800 million is needed annually for [grant] funding." In particular, the estimated 400 SMEs that are involved in antibiotic R&D need more direct funding.

By itself, increased grant funding cannot fill the pipeline. "[It] pays for R&D costs but does not improve the attractiveness of the overall market," Drive-AB said. Without pull incentives in the form of market entry awards, "antibiotic-resistant infection risks becoming a neglected disease, solely dependent on public and philanthropic finance."