WINS AND LOSSES FOR ANTIBIOTIC INNOVATION, BUT MORE EFFORTS NEEDED

11 October 2012

The U.S. and EU have taken strikingly different approaches toincentivizing antibiotic R&D. While Europe has raised 223.7 million Euros to starta public-private antibiotic researchpartnership, the U.S. has added five more years of data exclusivity for qualifying antibiotics. As explained by ReAct’s Strategic Policy Unit in a recent editorial, and echoed by others such as EFPIA’s Richard Bergström, extended exclusivityexacerbates the misalignment of economic incentives by tying returns on R&D investment to increased sales volume.

Incentives for novel antibiotics garnered attention on both sides of the Atlantic over the past couple months though Europe and the United States took strikingly different approaches. On the U.S. side, the Generating Antibiotic Incentives Now (GAIN) Act piggybacked onto a must-pass bill to reauthorize FDA user fees. The bill adds five more years of data exclusivity to certain qualified antibiotics and antifungal agents.

This incentive runs counter to the approach of finding otherways of securingreturns on investment than sales. This idea of delinking the twohas been embraced by the European Federation of Pharmaceutical Industries and Associations and by the recently released recommendations of the WHO’s Consultative Expert Working Group on Research and Development: Financing and Coordination. And risking rationing by price rather than rational use, it also threatens to be another stumbling block to timely availability and affordability of such drugs in developing countries.

Passed into law, the bill was opposed by Public Citizen, one of the country’s leading consumer groups, and the American Medical Student Association, representing the nation’s largest group of physicians-in-training. In a trenchant critique, Public Citizen pointed out how the bill might well grant monopoly protections based on test-tube and animal studies not adequate for determining whether drugs really fulfilled an unmet medical need, extended “exclusivity and priority review to antifungal drugs in the absence of any evidence that these drugs need such incentives,” and failed to “include provisions to promote the good stewardship and judicious use of antibiotics.”Similarly, Kevin Outterson also noted the legislation’s lack of measures to ensure conservation or rational use in an APUA newsletter op-ed titled, “All Pain, No GAIN: Need for Prudent Antimicrobial Use Provisions to Complement the GAIN Act.”

EFPIA’s Director General, Richard Bergstrom, weighed in on the debates, saying in the Wall Street Journal: “We are not convinced that patent term extension, as is essentially the US proposal, will work in practice. Imagine that you have developed a new antibiotic against a multi-resistant bacteria: You would be expected by everyone to be prudent with your marketing and control the usage to ‘reserve’ your new antibiotic. Even with 100 year patents, you will not make any money if you do not sell.”

ReAct Strategic Policy Unit Director Anthony So and Public Citizen President Robert Weissman wrote in the Huffington Postthat the bill “defies both the economics and biology of antibiotic resistance,” and in failing to address the scientific bottlenecks in the R&D pipeline, reflected a “poverty of policy imagination.” By contrast, at the same time, the European Union collaborating with the drug industry emerged with a plan that in its initial stage will bring 223.7 million Euros (US$280 million) to support the creation of a European public-private partnership for the development of novel antibacterial agents, from leads to candidates successful in Phase 1 clinical trials. The program, called NewDrugs4BadBugs (ND4BB), will be funded by the Innovative Medicines Initiative (IMI) with a matching in-kind contribution from the pharmaceutical industry.Still, the ND4BBat present lacks provisions to secure rational use of any new antibiotic forthcoming from the program. However, giving some hope for the future, the 6^th call text states:“The ND4BB programmeis also expected to be expanded in the future Calls with further research topics that will include the discovery of new molecular entities for the treatment of Gram–negative pathogens, and may include discovery of robustly validated host (human) targets for bacterial infections, regulatory/responsible use of antibiotics, and additional clinical development programmes”[emphasis added]. The next step in the N4DBB program was recentlyrevealed to focus on discovery and development of novel antibacterial drugs against Gram-negative infections, validating the outline mentioned in the 6^th call text.

Speaking for AstraZeneca, Basilea, GlaxoSmithKline, Johnson & Johnson and Sanofi, David Payne and Seamus O’Brien described the need for greater public-private collaboration and called for “information sharing amongst collaborators in a way we have never done before,” biomarker research and rapid diagnostics that could speed patient enrollment and lead to smaller and more efficient clinical trials, the “creation of a clinical trial consortium for antibacterials,” and a partnership with EU academics to “enable more rational approaches to design antibiotics for Gram-negative bacteria”Despite this promising move on the European side, all agree that much more needs to be done, particularly on the U.S. side, to stimulate antibiotic innovation. As Anthony So and Robert Weissman admonished: “The greatest cost, though, may be the complacency that comes with believing that Congress addressed antibiotic resistance with this measure. Even with the GAIN Act's passage, this public health challenge will still remain: Tomorrow's infections will not be cured with this expensive placebo.”

Responding to the reporting requirements under the GAIN Act, the FDA has created an internal task force to address four priorities: exploring novel approaches to antibiotic development; identifying unmet needs and the reasons that the pipeline has failed to meet them; reviewing existing FDA guidance and determining if changes are needed; and working with "existing collaborators to explore development." To the extent that this group may give greater focus to regulatory bottlenecks, this may complement the existing Interagency Task Force on Antimicrobial Resistance that released "A Public Health Action Plan to Combat Antimicrobial Resistance", which includes a focus on research and product development across federal agencies.

Although significant efforts have been made, finding efficient ways to preserve the effectiveness of antibiotics has proven difficult in practice. The topic of how to handle any future new antibiotics, i.e., a strong approach to their rational use, including a system for controlled distribution and dispensing, is a difficult one. Right now it may be the most important yet the weakest link in a “new business model” for the development of new antibiotics. It will require not only innovative policies for balancing adequate access to antibiotics against excessive antibiotic consumption--sensitively contextualized--but also strong commitment by the pharmaceutical industry, national governments, local authorities, and civil society to ensure global accessibility and affordability.

ReAct, together with other concerned stakeholders, has recently started a process with the aim to start identifying a set of policy interventions to prevent the misuse of novel antibiotics and support access, affordability and prudent use.

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