AKAO 2017 Annual Report

8 5,500 U.S. patients, the average incremental per-patient hospital cost for antibiotic-resistant healthcare-associated infections, as compared to antibiotic-susceptible infections, was over $15,000. According to government agencies and physician groups such as the CDC and the Infectious Disease Society of America, one of the greatest needs is for new antibiotics to treat infections caused by drug-resistant gram- negative pathogens, including ESBL-producing Enterobacteriaceae, CRE, Pseudomonas aeruginosa , and Acinetobacter baumannii . These pathogens are associated with significant morbidity and mortality, as growing antibiotic resistance has left limited effective treatment options. Governments, in collaboration with the private sector, have begun to respond to this significant and growing unmet medical need by creating governmental and non-governmental entities tasked with addressing the problem and progressing legislation for reimbursement and regulatory reform, and economic incentives. In the United States, the federal government has developed a National Action Plan for Combating Antibiotic Resistant Bacteria, which outlines Federal activities over the five-year period from 2015 to 2020 designed (i) to enhance domestic and international capacity to prevent and contain outbreaks of antibiotic-resistant infections; (ii) to maintain the efficacy of current and new antibiotics; and (iii) to develop and deploy next-generation diagnostics, antibiotics, vaccines, and other therapeutics. The National Action Plan proposes to accelerate research and development for new antibiotics through a multifaceted approach that includes intensified support for antibiotic product development from the NIH, BARDA, and the DOD’s Defense Threat Reduction Agency (“DTRA”). Accordingly, the 2018 U.S. federal budget request includes $1.02 billion for BARDA of which $192 million is to support the combating antimicrobial resistant bacteria initiative. The federal government has also established the Presidential Advisory Council on Combating Antibiotic Resistant Bacteria, a federal advisory committee, which is designed to provide advice, information, and recommendations to the Secretary of Health and Human Services on programs and policies related to combating antibiotic-resistant bacteria. On the legislative front, in July 2012, the Federal Drug and Administration Safety and Innovation Act (“FDASIA”) was passed, which included the Generating Antibiotics Incentives Now Act (the “GAIN Act”). The GAIN Act provides incentives for the development of new QIDP, including potential for priority review and the potential for adding five years to the otherwise applicable regulatory exclusivity period. In December 2016, the 21st Century Cures Act (the “Cures Act”) was passed by Congress and signed into law. This is a significant piece of legislation which is intended to modernize the regulation of drugs and spur innovation in biomedical research. Certain sections of the Cures Act support the development of new antibacterials targeting drug-resistant bacterial infections. Of note, the legislation establishes a mechanism to help streamline the development of certain antibacterial and antifungal drugs that are intended to treat serious or potentially fatal infections in limited populations of patients where unmet need exists due to lack of available therapies. Approval of these antimicrobials are expected to rely on data primarily targeting these limited populations, permitting FDA to approve such drugs for limited patient populations, notwithstanding a lack of evidence to fully establish a favorable benefit-risk profile in a population that is broader than the intended limited population. The statement “Limited Population” will appear prominently next to the drug’s name in labeling, which will provide notice to healthcare providers that the drug is indicated for use in a limited and specific population of patients. The limited population statement, additional labeling statements describing the data, and FDA review of promotional materials, are intended to help assure these drugs are used narrowly to treat these serious and life-threatening infections while additional evidence is generated to assess safety and effectiveness for broader use.