Durata Therapeutics Presents New Pivotal Phase 3 Clinical Results and New In Vitro Data on Dalbavancin at ICAAC
DENVER, Sept. 10, 2013 (GLOBE NEWSWIRE) — Durata Therapeutics, Inc. (Nasdaq:DRTX) today presented clinical trial results from its two Phase 3 DISCOVER (“Dalbavancin for Infections of the Skin COmpared to Vancomycin at an Early Response”) 1 and 2 studies and new in vitro data of dalbavancin, further characterizing the effect of the investigational treatment against Gram-positive bacteria. In the two randomized, double-blind clinical studies, dalbavancin was shown to be non-inferior to the comparator regimen, vancomycin with an option to switch to oral linezolid, in treating acute bacterial skin and skin structure infections (ABSSSI).i, ii In both studies, dalbavancin met its primary and secondary endpoints. Further, recipients in the dalbavancin arms of the studies had fewer treatment emergent adverse events than those in the comparator arms.i, ii The in vitro data showed activity against Staphylococcus aureus strains, including methicillin-resistant strains (MRSA), recovered from patients with osteomyelitis-related wounds.iii The data were presented in three separate posters at the 53rd Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC) in Denver, CO.
Dalbavancin is a novel antibacterial under investigation for the treatment of ABSSSI caused by susceptible Gram-positive microorganisms, such as Staphylococcus 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.
The specific infections in the DISCOVER 1 and 2 studies included cellulitis, major abscess and wound infection (approximately 50%, 30% and 20% across treatment groups, respectively).i, ii The median lesion size at baseline was >300 cm2.i, ii In addition to local signs and symptoms of infection, patients were also required to have at least one systemic sign of disease at baseline, defined as temperature >38?C, white blood cell count >12,000 cells/mm3 or ?10% band forms on white blood cell differential (approximately 85%, 40% and 23% across treatment groups, respectively).i, ii Approximately 50% of patients met the criteria for Systemic Inflammatory Response Syndrome (SIRS).i, ii In DISCOVER 1, approximately 20% of patients were treated in the outpatient setting,i while in DISCOVER 2, approximately 27% were similarly treated.ii
“Dalbavancin appears to bring us results comparable to a standard regimen. This is especially impressive because the patients in these studies had more severe ABSSSI than seen in recent registrational studies, including very large skin lesions and high frequencies of fever and systemic inflammatory response syndrome (SIRS). With once-weekly dosing, this opens up the prospect of treating some patients outside of the most expensive clinical setting—the hospital,” 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 program.
The DISCOVER data will be used to support the company’s anticipated submission of a New Drug Application (NDA) to the U.S. Food and Drug Administration (FDA). Trials were conducted via a special protocol agreement based on the FDA’s Draft Guidance for Developing Drugs for the Treatment of ABSSSI. The protocol for the studies was also designed based on scientific advice provided by the European Medicines Agency (EMA).
“As our first product candidate, dalbavancin reflects Durata Therapeutics’ commitment to providing innovative and new solutions to treat acute illnesses and infectious diseases,” said Paul R. Edick, Durata Chief Executive Officer. “We are on track to submit our NDA for dalbavancin with the FDA by the end of September 2013.”
Durata Therapeutics is studying dalbavancin against a range of infections, as detailed in the posters it presented today at ICAAC:
DISCOVER 1 (L-201) and DISCOVER 2 (L-202): A Randomized, Double-blind Study of Dalbavancin (DAL) compared to Vancomycin (V) (with an option to switch to Linezolid (L)) in Treatment of Acute Bacterial Skin and Skin Structure Infections (ABSSSI)
The DISCOVER studies are identically designed multicenter, double-blind, randomized clinical trials that included more than 1,300 adults with ABSSSI from the United States, Europe, Asia and South Africa. In the DISCOVER studies, adult 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. Dalbavancin achieved its primary endpoint in both the DISCOVER 1 and DISCOVER 2 studies of non-inferiority to vancomycin/linezolid by demonstrating cessation of spread of the erythema associated with the lesion, as well as the resolution (absence) of fever 48-72 hours following initiation of treatment.i, ii The secondary endpoint of clinical success at end of treatment (EOT), the expected primary endpoint for regulatory review in Europe, was also met.i, ii
Per pathogen clinical success rates were high and comparable across treatment groups at end-of-therapy and at short-term follow-up.i, ii
The rates of serious adverse events and study drug discontinuations for dalbavancin and comparator treated patients were similar. The most commonly reported adverse events in DISCOVER 1 (D1) and DISCOVER 2 (D2) for dalbavancin and vancomycin/linezolid respectively, were nausea (D1: 4.2% vs 4.6%, D2: 4.1% vs 4.1%), diarrhea (D1: 1.4% vs 3.9%, D2: 1.1% vs 2.2%), headache (D1: 4.9% vs 4.9%, D2: 3.0% vs 2.5%), pruritus (D1: 0.4% vs 3.9%, D2: 1.4% vs 1.9%), hypertension (D1 only: 2.5% vs 2.5%), rash (D1 only: 2.1% vs 2.1%), asthenia (D1 only: 0.4% vs 2.1%), and vomiting (D2 only: 2.2% vs 1.1%).i, ii
In Vitro Activity of Dalbavancin Against Consecutive Isolates of Staphylococcus Species Recovered from Osteomyelitis Infections
Demonstrating the in vitro antibacterial activity of dalbavancin against a variety of Staphylococcus species, researchers collected samples from patients with osteomyelitis-related wounds and tested them in the laboratory against multiple antimicrobial agents. Forty-one strains of Staphylococcus (methicillin-sensitive Staphylococcus aureus or MSSA; S. lugdunensis; S. epidermidis and MRSA) were grown overnight for testing and treated with dalbavancin, daptomycin, doxycycline, levofloxacin, linezolid, rifampin, vancomycin or trimethoprim-sulfamethoxazole. Dalbavancin was the most active agent tested by weight other than rifampin and was effective at inhibiting visible staph growth at a lower concentration than vancomycin and daptomycin, two common antibiotics used to treat staphylococcal infections.iii Potency at lower concentrations is important because it reduces the chances of generating bacterial resistance (dalbavancin was 16 times more potent than vancomycin and 4 to 8 times more potent than daptomycin).iii The study was conducted by R.M. Alden Research Lab and supported by a grant from Durata Therapeutics.
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.iv This category of infection increased by 176 percent from 1997 to 2009 in hospitalized patients.v 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.vi,vii Effective early treatment of ABSSSI is critical to prevent wound expansion and to avoid lengthy and costly hospital stays.viii 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.
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 or long duration of antibacterial activity of 5-7 days per dose.ix If approved, dalbavancin would be the first drug for ABSSSI requiring only two once-weekly 30-minute intravenous doses (1000 mg on Day 1 and 500 mg on Day 8). 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.x Ultimately, this may lower the overall cost of care for these patients.
ABOUT DURATA THERAPEUTICS, INC.
Durata Therapeutics, Inc. is a pharmaceutical company focused on the development and commercialization 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, for the treatment of patients with acute bacterial skin and skin structure infections, or ABSSSI.
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 forward-looking statements, although not all forward-looking statements contain these identifying words.
Forward-looking statements in this press release include statements about the timing of the submission of a NDA with the FDA and potential impact of dalbavancin use on hospital costs and readmissions. 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 statements as representing our views as of any date subsequent to today.
i Boucher/DISCOVER-1 ICAAC Poster/2013
ii Wilcox/DISCOVER-2 ICAAC Poster/2013
iii Citron/In Vitro ICAAC Poster/2013
iv AMR Hospital Antibiotic Market Guide – Book 2: Diagnosis and Surgery Reports, January 2010 – June 2010.
v 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).
vi 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).
vii 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).
viii 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).