AKAO 2017 Annual Report

12 Enterobacteriaceae are approximately 57% more likely to die than those with BSI caused by a non ESBL-producing strain. Commercial Strategy for Plazomicin Our overall goal is to establish plazomicin as the standard of care for the treatment of serious bacterial infections due to MDR Enterobacteriaceae, including CRE. Our strategy is intended to support plazomicin’s differentiated profile from both approved and development-stage antibacterials. Our clinical development program is focused on the treatment of serious bacterial infections due to Enterobacteriaceae in patients with limited or no alternative treatment options. The submission of an NDA to the FDA for plazomicin, seeking approval to treat cUTI, including AP, and BSI due to certain Enterobacteriaceae in patients who have limited or no alternative treatment options, was accepted by the FDA and granted NDA Priority Review as well as a PDUFA target action date of June 25, 2018. The NDA is supported by data from two Phase 3 clinical trials, EPIC and CARE. Given the lack of effective therapeutic options and the increasing rates of gram-negative infections such as CRE and those caused by ESBL-producing bacteria, we believe the commercial opportunity for plazomicin is significant. We anticipate that the effectiveness of plazomicin in our Phase 3 program, along with extensive data describing plazomicin’s microbiological activity and PK/PD properties, will create significant physician demand for plazomicin based on our primary market research. A demonstrated efficacy and safety benefit versus colistin in a patient population with a high risk of death due to CRE infections, and favorable outcomes compared to a carbapenem in treating cUTI/AP, will be key product differentiators that drive adoption. If approved, we expect that the pricing and reimbursement for plazomicin will reflect the strong clinical data and the lack of effective treatment options for gram-negative infections such as CRE and ESBL-producing bacteria. At a 2013 forum sponsored by The Pew Charitable Trusts, a nonprofit organization, which brought together payors, the FDA, and industry representatives, panelists indicated support for an approximate price point of $15,000 per course of therapy for new antibacterial agents for resistant infections as long as clinical and economic benefits were clearly demonstrated. For comparison, recently launched ceftazidime-avibactam and meropenem-vaborbactam currently cost approximately $1,000 per day reflecting a course of therapy from $10,000 to $14,000. If approved, we expect physicians to consider using plazomicin for definitive treatment of patients with MDR gram-negative pathogens, including CRE and ESBL-producing pathogens, as well as for empiric treatment, or treatment prior to definitive confirmation of the pathogen, of patients who are at risk of CRE. Definitive treatment for CRE begins when the infecting pathogen has been confirmed as CRE. Length of therapy with plazomicin was 5- 7 days in EPIC for cUTI and 7-14 days for patients with either BSI or pneumonia. We estimate that there were approximately 180,000 cases of confirmed CRE infections in the United States and the EU 5 in 2016 of which 70,000 to 80,000 were in the United States. Given the importance of providing effective CRE therapy as soon as possible in order to reduce the risk of death, if approved, we believe physicians will consider using plazomicin empirically to treat patients who are at a high risk of CRE infection and at hospitals with high rates of CRE. Empiric treatment continues until the pathogen is confirmed, which typically takes 2 to 3 days. Following pathogen confirmation, definitive treatment begins either with the same drug(s) used for empiric treatment or with different drug(s), depending on numerous factors including the identity and susceptibility of the pathogen, as well as patient response to empiric therapy. We estimate the total number of cUTI, pneumonia or BSI diagnosed in the United States and EU 5 was approximately 11.0 million in 2016. This smaller subset of empirically treated patients is a more relevant population in which plazomicin might be prescribed to provide empiric treatment for CRE, depending on a number of CRE risk factors, including patient colonization with CRE and high incidence of CRE in the hospital unit. If approved, we intend to focus our initial commercial efforts on the U.S. market, which we believe represents the largest single market opportunity for plazomicin. We plan to use a targeted U.S. sales force to promote plazomicin to hospital-based healthcare professionals where MDR infections, including CRE, are concentrated in resistance hotspots, including New York City, Los Angeles and Chicago, and other major population centers. In key markets outside of the United States, including Europe, Asia, and Latin America, we currently believe we can expand the value of plazomicin through collaborating with one or more global or regional commercialization partners who have local market expertise.