October 2, 2013 Durata Therapeutics Presents New Comprehensive Review of the Efficacy and Safety Data of Dalbavancin and New In Vitro Findings at IDWeek 2013 SAN FRANCISCO, Oct. 2, 2013 (GLOBE NEWSWIRE) -- Durata Therapeutics, Inc. (Nasdaq:DRTX) today announced a comprehensive review of the efficacy, safety and microbiology data of the company's lead product candidate, dalbavancin, for the treatment of patients with acute bacterial skin and skin structure infections (ABSSSI). The data is being presented in six posters at this year's IDWeek 2013, held in San Francisco, Calif., October 2-6, 2013. Among the findings, an integrated analysis of two Phase 3 clinical studies (DISCOVER 1 and 2) showed dalbavancin met its primary and secondary endpoints of early response, measured at 48 to 72 hours of therap y, as well as clinical success at the end of treatment. Sensitivity analyses for both timepoints were also included. i A separate analysis showed that patients achieving cessation of spread of the lesion after 72 hours of antibiotic treatment with dalbavancin have a greater than 90 percent chance of being cured at the end of treatment. ii A pooled summary analysis of the safety profile of dalbavancin based on the Phase 2 and 3 clinical program also found it to be generally well-tolerated and to have a similar safety profile to comparators with fewer adverse events. iii Examination of patients with baseline Gram-positive bacteremia enrolled in the dalbavancin clinical development program as well as in vitro activity against methicillin-resistant Staphylococcus aureus (MRSA) and Neisseria gonorrhoeae were also presented. "The data show that dalbavancin has the potential to be an efficacious and well-tolerated treatment option for patients with ABSSSI," said Durata Therapeutics Chief Medical Officer Michael Dunne, M.D. "Our studies were designed to meet the new standards required by regulatory authorities for antibiotic development in the United States and European Union and support our New Drug Application submission to the Food and Drug Administration late last week." Dalbavancin is a novel antibacterial under investigation for the treatment of ABSSSI caused by susceptible Gram-positive microorganisms, such as S. aureus (including MRSA
and other multi-drug resistant strains) and Streptococcus pyogenes, as well as certain other streptococcal species. Dalbavancin is bactericidal against Gram-positive bacteria and is administered with a once-weekly dosage regimen of 1000 mg on Day 1 and 500 mg on Day 8, over 30 minutes by intravenous infusion. Copies of the following posters will be available on Durata Therapeutics' website: www.duratatherapeutics.com. Poster # 1339: An Integrated Analysis of the Efficacy of Dalbavancin for the Treatment of Acute Bacterial Skin and Skin Structure Infections (ABSSSI) in the DISCOVER Program i (Date: October 5, 2013) Data were presented from an integrated analysis of the efficacy results from the DISCOVER ("Dalbavancin for Infections of the Skin COmpared to Vancomycin at an Early Response") program and found that dalbavancin is non-inferior to the comparator regimen at both an early timepoint and at the end of therapy. The DISCOVER program includes two Phase 3 identically designed multicenter, double-blind, randomized clinical trials of more than 1,300 adult patients with ABSSSI from the United Stat es, Europe, Asia and South Africa. Patients were treated for two weeks either with intravenous dalbavancin once weekly (1000 mg on Day 1 followed by 500 mg on Day 8) or with intravenous vancomycin (1000 mg or 15 mg/kg every 12 hours) with the option to switch to oral linezolid after three days. Primary endpoints from the DISCOVER trials were cessation of spread of the erythema associated with the lesion and resolution of fever measured at 48-72 hours per FDA requirements. While a secondary endpoint for FDA, clinical success at end of treatment is the expected primary endpoint for regulatory review in Europe. Examining both endpoints provides clinicians with correlation between the early and late findings. The integrated efficacy analysis found that: Dalbavancin had similar efficacy rates relative to the comparator regimen in demonstrating the combination of cessation of lesion spread and absence of fever 48-72 hours following initiation of treatm ent Success rates at the Day 14 end of treatment and the Day 28 follow up visit were similar in both treatment groups Poster # 1340: Concordance of Clinical Response at 48-72 Hours after Initiation of Therapy and End of Treatment (EOT) in Patients with Acute Bacterial Skin and Skin Structure Infection (ABSSSI) in the DISCOVER Studies ii (Date: October 5, 2013) An additional analysis of the DISCOVER clinical trials examined the concordance of study endpoints (i.e., clinical response at 48-72 hours after initiation of therapy as well as at the end of treatment) and found that the majority of early responders were ultimately cured. Specifically, the analysis found that: The majority (945/1,046, 90.3%) of patients who responded favorably to treatment
with dalbavancin by 48 to 72 hours were ultimately cured by the end of treatment Most (129/182, 70.9%) patients who were non-respond ers on Day 3 were also subsequently cured by the end of treatment Patients who do not achieve cessation of lesion spread at 72 hours alone and have worsening pain have an 80 percent chance of ultimately failing treatment "The early assessment timepoint recommended by the FDA was put in place to guide antibiotic drug development for ABSSSI," said Mark Wilcox, M.D., Head of Microbiology, Leeds Teaching Hospitals and Professor of Medical Microbiology at the University of Leeds, UK and an advisor to the DISCOVER clinical trial program. "These data, however, may also give physicians confidence at an early timepoint that could help identify patients who could ultimately be cured and those who might fail." Poster # 1343: Clearance of Staphylococcus aureus Bacteremia in Patients Treated with Dalbavancin iv (Date: October 5, 2013) Data collected from three Phase 3 trials with skin and skin str ucture infections and one Phase 2 catheter-related infection study support the use of dalbavancin in patients with skin infections who also have a bacteremia at baseline. Blood cultures were drawn at baseline from two anatomical sites and not through an existing intravenous line. If positive at baseline, blood cultures were to be repeated every 48-72 hours until negative. Comparators included vancomycin and linezolid. The study found that: All patients in the dalbavancin group with baseline Gram-positive bacteremia, including those with S. aureus, (n=71) who had follow-up blood cultures available (n=61), had documented clearance of their bacteremia and clinical outcome rates at end of treatment similar to comparators Poster # 1334: An Analysis of the Safety Profile of Dalbavancin from the Phase 2/3 Clinical Program iii (Date: October 5, 2013) In the most comprehensive review of safety data f rom dalbavancin's clinical program todate, including Phase 2 and Phase 3 clinical trials of more than 3,000 patients, data showed that dalbavancin is safe and generally well-tolerated relative to comparator agents used for treatment of skin infections. A substantial proportion of patients were enrolled from the United States (64.3%), younger than age 65 (82.4%), white (78.1%) and overweight (71.6%) and should reflect the intended population of patients with these types of infections in clinical practice. The integrated safety analysis found that: The percentage of subjects with treatment emergent adverse events, the frequency of treatment emergent adverse events and the adverse event burden experienced by patients in the dalbavancin group were lower than those in the comparator treatment group The duration and time to onset of treatment emergent adverse events was similar in the dalbavancin and comparator groups
The most commonly reported adverse events for dalbavancin or the comparator respectively, included nausea (2.8% vs. 3.3%), diarrhea (2.5% vs. 3.7%), headache (1.5% vs. 1.6%), elevated gamma-glutamyl transferase (1.1% vs. 1.0%), rash (1.0% vs. 1.1%), vomiting (1.0% vs. 0.9%) and pruritus (0.6% vs. 1.9%) Poster # 1338: Microbiologic Analyses of Target Pathogens Identified in the Dalbavancin DISCOVER Program v (Date: October 5, 2013) Target pathogens isolated at baseline from the DISCOVER clinical trials were tested in vitro for susceptibility to a panel of antibiotics, including dalbavancin. The study demonstrated the potent in vitro activity of dalbavancin against key Gram-positive pathogens, including MRSA (n=273), MSSA (n=396) and streptococci (n=151) causing ABSSSI. Specifically, the study found that: The MIC 90 of dalbavancin for S. aureus, whether MRSA or MSSA, was less than or equal to 0.06 µg/ml The MIC 90 of dalbavancin for target streptococci was less than 0.06 µg/ml Poster # 255: In Vitro Activity of Dalbavancin against Neisseria gonorrhoeae and Development of a Broth Microdilution Method vi (Date: October 3, 2013) A study examined the in vitro activity of dalbavancin against a challenge set of N. gonorrhoeae declared an urgent threat by the Centers for Disease Control and Prevention vii and found that the in vitro activity of dalbavancin against N. gonorrhoeae by broth microdilution is an indication of possible in vivo activity that will require further investigation. Given that antibiotic susceptibility testing for dalbavancin is performed in broth, efforts were made to explore methodologies to understand growth of N. gonorrhoeae in broth rather than agar. Dalbavancin, ceftriaxone and ciprofloxacin broth microdilution and agar dilution MIC results were obtained for a set of 31 N. gonorrhoeae (11 susceptible strains including quality control strain ATCC 49226 and 20 resistant strains) and quality control S. aureus ATCC 29213. A modified gonococcus (GC) broth (substitution of glucose instead of starch) + 0.002 percent polysorbate 80 was used for testing of dalbavancin and GC broth was used for the two comparator agents. All MIC plates were incubated in CO 2 and results were read after 48 hours. The study found that: Dalbavancin BMD MICs (48 hours in 5% CO 2 ) were 0.12-1 µg/ml with a MIC90 of 0.5 µg/ml The addition of 0.002% P-80 to modified GC broth provides N. gonorrhoeae dalbavancin MIC results that are on average 3 dilutions lower compared to AD results Further development to determine the optimal broth and incubation condit ions are necessary This study was conducted by Dr. Laura Koeth, Laboratory Specialists, Inc., and sponsored
by a grant from Durata Therapeutics. About ABSSSI For the six month period of January to June 2010, a projected 9.2 million patients were treated in U.S. hospitals for infections of any type, and nearly 17 percent of the diagnostic category presentations were for skin and skin structure infections (SSSIs). Of these presentations for SSSI, approximately 74 percent were disease types included in ABSSSI. viii This category of infection increased by 176 percent from 1997 to 2009 in hospitalized patients. ix The majority of skin and soft tissue infections in hospitalized patients are caused by Staphylococcus aureus and approximately 59 percent of these infections are estimated to be caused by MRSA in the U.S. x,xi Effective early treatment of ABSSSI is critical to prevent wound e xpansion and to avoid lengthy and costly hospital stays. xii Failure to successfully treat ABSSSI may result in hospital readmissions. Under the new health care reform laws, hospitals may incur financial penalties for preventable hospital readmissions, including unresolved infections. About N. Gonorrhoeae Neisseria gonorrhoeae causes gonorrhea, a sexually transmitted disease that can result in discharge and inflammation at the urethra, cervix, pharynx or rectum. Gonorrhea is the second most commonly reported notifiable infection in the United States and is easily transmitted. N. gonorrhoeae is showing resistance to the antibiotics typically used to treat it. The CDC estimates there are at least 246,000 cases of drug-resistant N. gonorrhoeae each year, and recently assigned it to an urgent hazard level in its report "Antibiotic resistance threats in the United States, 2013." vii About Dalbavancin Dalbavancin is a second generation, semi-synthetic lipoglycopeptide, which consists of lipophilic side-chains attached to glycopeptides. When compared to vancomycin, dalbavancin has a longer half-life resulting in a duration of antibacterial activity of 5-7 days per dose. xiii If approved, dalbavancin would be the first drug for ABSSSI requiring a onceweekly dosage regimen of 1000 mg on Day 1 and 500 mg on Day 8, over 30 minutes by intravenous infusion. This may allow for the treatment of patients with ABSSSI in both inpatient and outpatient settings potentially shortening the length of patient hospital stays, or in some cases, eliminating hospital admissions altogether. xiv Ultimately, this may lower the overall cost of care for these patients. About Durata Therapeutics, Inc. Durata Therapeutics is a pharmaceutical company focused on the development and commer cialization of novel therapeutics for patients with infectious diseases and acute illnesses. Durata has completed two global Phase 3 clinical trials with its lead product
candidate, dalbavancin, under investigation for the treatment of patients with acute bacterial skin and skin structure infections caused by susceptible Gram-positive bacteria. About IDWeek 2013 IDWeek 2013 is an annual meeting of the Infectious Diseases Society of America (IDSA), the Society for Healthcare Epidemiology of America (SHEA), the HIV Medicine Association (HIVMA) and the Pediatric Infectious Diseases Society (PIDS). With the theme "Advancing Science, Improving Care," IDWeek features the latest science and bench-tobedside approaches in prevention, diagnosis, treatment, and epidemiology of infectious diseases, including HIV, across the lifespan. IDWeek 2013 takes place October 2-6 at the Moscone Center in San Francisco, California. The full name of the meeting is IDWeek 2013. For more information, visit www.idweek.org. Forward-looking Statements Statements contained in this press release contain forward-looking statements that involve substantial risks and uncertainties. All statements, other than statements of historical facts, contained in this press release, including statements regarding our strategy, future operations, future financial position, future revenues, projected costs, prospects, plans and objectives of management, are forward-looking statements. The words "anticipate," "believe," "estimate," "expect," "intend," "may," "plan," "predict," "project," "target," "potential," "will," "would," "could," "should," "continue," and similar expressions are intended to identify f orward-looking statements, although not all forward-looking statements contain these identifying words. Forward-looking statements in this press release include statements about the potential FDA approval of dalbavancin and the impact of once-weekly dosing of dalbavancin. Actual results may differ materially from those indicated by these forward-looking statements as a result of various important factors, including those discussed in the "Risk Factors" section of our most recent quarterly report on Form 10-Q, which is on file with the SEC and is also available on our website. In addition, any forward-looking statements represent our views only as of today and should not be relied upon as representing our views as of any subsequent date. While we may elect to update these forward-looking statements at some point in the future, we specifically disclaim any obligation to do so, even if our views change. Therefore, you should not rely on these forward-looking stateme nts as representing our views as of any date subsequent to today. References i Wilcox M, Boucher H et al. An Integrated Analysis of the Efficacy of Dalbavancin for the Treatment of Acute Bacterial Skin and Skin Structure Infections (ABSSSI) in the DISCOVER Program. IDWeek Poster #1339 (2013). ii Dunne M, Puttagunta S et al.concordance of Clinical Response at 48-
72 Hours after Initiation of Therapy and End of Treatment (EOT) in Patients with Acute Bacterial Skin and Skin Structure Infection (ABSSSI) in the DISCOVER Studies. IDWeek Poster #1340 (2013). iii Dunne M, Das A et al. An Analysis of the Safety Profile of Dalbavancin from the Phase 2/3 Clinical Program. IDWeek Poster #1334 (2013). iv &nb sp; Dunne M, Puttagunta S et al. Clearance of Staphylococcus aureus Bacteremia in Patients Treated with Dalbavancin. IDWeek Poster #1343 (2013). v Dunne M, Boucher H et al. Microbiologic Analyses of Target Pathogens Identified in the Dalbavancin DISCOVER Program. IDWeek Poster #1338 (2013). vi Koeth L, Fisher J. In vitro Activity of Dalbavancin against Neisseria gonorrhoeae and Development of a Broth Microdilution Method. IDWeek Poster #255 (2013). vii Centers for Disease Control and Prevention. Antibiotic Resistance Threats in the United States, 2013. (2013). viii AMR Hospital Antibiotic Marke t Guide - Book 2: Diagnosis and Surgery Reports, January 2010 June 2010. ix Giuliano C, Kale-Pradhan P, et al. Early Response of Ceftaroline Fosamil in the Treatment of Soft-tissue Infections. Expert Rev Clin Pharmacol. 5(5):509-512 (2012). x Moet G, Jones R, et al. Contemporary causes of skin and soft tissue infections in North America, Latin America and Europe: Report from the SENTRY Antimicrobial Surveillance Program (1998-2004). Diagnostic Microbiology and Infectious Disease. 57, 7-13 (2007). xi Moran GJ, Krishnadasan A, Gorwitz RJ et al. EMERGEncy ID Net Study Group. Methicillin-resistant S. aureus Infections Among Patients in the Emergency Department. N. Engl. J. Med. 355(7), 666 674 (2006). r xii Parta M, M Goebel et al. Impact of an Assay That Enables Rapid Determination of Staphylococcus Species and Their Drug Susceptibility on the Treatment of Patients with Positive Blood Culture Results. Infect. Control and Hospital Epidemiology. 31(10), 1043-1048 (2010). xiii Durata DOF.
xiv Durata Therapeutics website. About dalbavancin. http://www.duratatherapeutics.com/product-pipeline/dalbavancin/overview (Durata DOF) CONTACT: Investor Relations and Public Affairs Contact Allison Wey Durata Therapeutics Vice President, Investor Relations and Public Affairs (312) 219-7017 awey@duratatherapeutics.com Media Relations Contact Geoff Curtis DJE Science (312) 233-1253 geoff.curtis@djescience.com Source: Durata Therapeutics, Inc.