Slide 1
A New ICD-10-PCS Code For the Administration of Dalbavancin

- Kenneth E. Johnson, PharmD
  Vice President, Corporate Medical Affairs
  Durata Therapeutics, Inc.

- ICD-10-CM/PCS Coordination and Maintenance Committee Meeting
  Centers for Medicare & Medicaid Services (CMS)
  March 19, 2014


Slide 2
Agenda

- Coding Issue

- Introduction to Durata Therapeutics

- ABSSSI:  Unmet medical need for the treatment of acute bacterial skin and skin structure infections 

- Overview of Dalbanvancin
	 Dosing and Administration
	 Efficacy and Safety
       
- Dalbavancin therapy and its role in ABSSSI 

- ABSSSI and ICD-10 Considerations


Slide 3
Coding Issue
       
Issue
- There is not a unique ICD-10-PCS code to describe the intravenous (IV) administration of dalbavancin to treat patients with acute bacterial skin and skin structure infections (ABSSSI) caused by Gram-positive bacteria, such as S. aureus, including Methicillin-Resistant and multi-drug resistant strains, and certain streptococcal species.

New Technology Application 
- Durata Therapeutics, Inc. submitted a New Technology Add-On Payment application for dalbavancin for fiscal year (FY) 2015. 

Food and Drug Administration (FDA) Approval 
- The New Drug Application (NDA) for dalbavancin was submitted to the FDA on September 26, 2013. Based on PDUFA regulations, the target date of regulatory approval is May 26, 2014. 


Slide 4
Durata Therapeutics: Introduction

- Durata Therapeutics, Inc., (Durata) is a pharmaceutical company focused on the development and commercialization of therapeutic solutions to advance patient care in infectious disease

- Established in 2009, Durata became a publicly traded company (NASDQ: DRTX) in March 2012 and is headquartered in Chicago, IL

- Durata is initially developing dalbavancin, an IV antibiotic product candidate, for the treatment of acute bacterial skin and skin structure infections (ABSSSI) and is investing in high-unmet need indications 

- Dalbavancin received a Qualified Infectious Disease Product (QIDP) designation by FDA on Nov	5, 2012.
	 Dalbavancin is among the first anti-infective agents to receive QIDP designation through the new Generating Antibiotic Incentives (GAIN) statute
	 The QIDP designation provides dalbavancin priority review by the FDA and eligibility for fast-track status


Slide 5
ABSSSI Indication: FDA Criteria

-ABSSSI are serious, bacterial infections of the skin with a lesion size area of at least 75 cm2
	 Infection types
		- Cellulitis/erysipelas
		- Wound infection (traumatic or surgical site)
		- Major cutaneous abscess
	 Accompanied by
		- Fever
		- Leukocytosis
		- And/or increased immature neutrophils
		- Each consistent with values defining the systemic inflammatory response syndrome [SIRS]

- Pathogens include Staphylococcus aureus and streptococci, mainly Streptococcus pyogenes
	 Over 50% of S. aureus involved in ABSSSI is methicillin-resistant (MRSA)

Slide 6
ABSSSI: The Ummet Medical Need

-Antimicrobial therapy practice patterns in ABSSSI:
	 IV vancomycin used in 75% patients
		 80% is administered intravenously during an inpatient stay; 50% through peripherally inserted central catheter (PICC)
	 Total duration of therapy (inpatient and outpatient) ranges 10 - 17 days
	 At discharge, patients will continue with IV therapy or switch to oral treatment

- Issues with existing options include:
	 Daily dosing limits potential for outpatient treatment with existing IV therapies
	 Vancomycin: efficacy concerns at higher minimum inhibitory concentration (MIC); dose limiting toxicities require drug monitoring
	 Daptomycin: development of resistance on therapy; rhabdomyolysis 
	 Linezolid: mitochondrial toxicity limits duration of treatment; serotonin syndrome liability

- Current challenges and unmet needs
	 Clinical failure (treatment failure, recurrence or readmission within 30 days) observed in 12% of ABSSSI patients
		- 63% of clinical failures with cellulitis cohort discharged on oral trimethoprim-sulfamethoxazole
	 PICC poses additional risks and complications 
		- Increased risk of bloodstream infection and venous thrombus formation
		- Emergency department visit (2%), re-hospitalization (1%), PICC replacement and fluoroscopic confirmation (5%), physician visit (17%), declotting procedure (7%) and administration of tissue plasminogen activator (7%)

Slide 7
Hospital Incidence of Acute Bacterial Skin and Skin Structure Infections (ABSSSI)

- U.S. hospitals treat ~18 million patients annually for infections

- ABSSSI accounts for ~17% of these infections, or 3.3M patients1

- ABSSSI represents ~3% of all admissions2

- ~1.3M (39%) of 3.3M ABSSSI patients are greater than equal to 65 years of age1

- Cellulitis and wound infections comprise the majority of clinical presentations

Sources: 
1 AMR Hospital Antibiotic Market Guide - Book 2: Diagnosis and Surgery Reports, January 2010  June 2010.
2 HCUP Data 2009.

Slide 8
Dalbavancin: Overview

- Dalbavancin is a semisynthetic lipoglycopeptide intravenous (IV) antibiotic that interferes with cell wall synthesis which results in bacterial cell death
	 Administered as a once-weekly 30 minute IV infusion 

- The pharmacokinetic profile of dalbavancin demonstrates rapid bactericidal activity that is potent and sustained against serious gram-positive infections including MRSA

- Dalbavancins long half-life provides a once-weekly treatment regimen and bactericidal concentrations are sustained throughout the dosing interval

- Once-weekly dosing allows for the discontinuation of IV access with its attendant risks of line related thrombosis and infection

- A complete course of therapy (14 days) consists of two doses of dalbavancin administered on Day 1 and Day 8

- Dalbavancin will be administered in both inpatient and outpatient settings of care

Slide 9
Proposed Indication and Usage

- DALVANCE (dalbavancin) for injection is indicated for the treatment of adult patients with	acute bacterial skin and skin structure infections (ABSSSI) caused by susceptible strains of the following Gram-positive microorganisms:
	 Staphylococcus aureus (including MSSA and MRSA)
	 Streptococcus pyogenes
	 Streptococcus agalactiae
	 Streptococcus anginosus group (including S. anginosus, S. intermedius, S. constellatus)

Slide 10
Dalbavancin is the First IV Antibiotic for ABSSSI with a Once-Weekly Dosage Regimen

- The recommended dosage regimen for dalbavancin in adult patients with ABSSSI is 1000 mg on Day 1 and 500 mg on Day 8, administered via an intravenous (IV) catheter over 30 minutes

- In clinical trials, dalbavancin was primarily delivered via peripheral line; however, administration	via central line may be clinically appropriate under certain circumstances or preferred by the physician or patient 

Slide 11
Use in Special Populations & Contraindications

- The dosage regimen for dalbavancin should be reduced to 750 mg on Day 1 and 375 mg on Day 8 in patients with chronic renal impairment whose creatinine clearance is <30 mL/min and who are not receiving regularly scheduled renal dialysis

- No dose adjustment for patients with mild hepatic impairment

- Pregnancy: Category C

- Of the adult patients (n=1778) treated with dalbavancin in Phase 2/3 clinical trials, efficacy & tolerability were similar to comparator regardless of age

- Safety and efficacy in pediatric patients have not been established

- Dalbavancin is contraindicated in patients with known hypersensitivity to dalbavancin or any of its components  

- No data are available on cross-reactivity between dalbavancin and other glycopeptides, including vancomycin


Slide 12
Efficacy and Safety Overview

- Dalbavancin achieved the primary non-inferiority efficacy endpoints in multiple Phase 3 ABSSSI clinical trials when tested against presently approved and appropriate standard-of-care comparators in relevant indications and patient populations

- Efficacy was durable when patients were followed for as long as 70 days after initiation of treatment

- Safety and tolerability were acceptable relative to each of the comparators

- Adverse events occurred less frequently in the dalbavancin treated patients and no dose-limiting toxicity was observed

- The duration of adverse events was similar to that of comparators and late onset adverse events were not identified as a concern

- Demonstrated consistent safety and efficacy in relevant subpopulations, such as the elderly and diabetic patients

Slide 13
Safety Profile

PHASE 2/3 DATA IN DALBAVANCIN CLINICAL PROGRAM

Adverse Event*, Dalbavancin n(%) (N = 1778), Comparator, n (%), (N = 1224), P value

Nausea, 49 (2.8), 40 (3.3), 0.441

Diarrhoea, 45 (2.5), 45 (3.7), 0.081

Pruritus, 11 (0.6), 23 (1.9), 0.002			

*Defined as treatment-related adverse events occurring in >2% of subjects in any dosing subgroup

Slide 14
Dalbavancin: Potential Impact On Current Standard Of Care in ABSSSI

- Compared to current standard of care administered once or twice per day, once-weekly dalbavancin has the potential to streamline process of care and lower total cost of care in both inpatient and outpatient treatment settings via:
	 Reduction in length of stay (emergency department and/or inpatient)
	 Avoidable admissions including skilled nursing facility stays for IV antibiotic dosing following a hospitalization 
	 Reduced risk of readmission
	 Avoidance of potential complications (i.e., PICC)

- Individual patient experience of care will also be improved
	 No need for indwelling catheter (i.e., PICC)
	 Built-in adherence to therapeutic regimen
	 Less patient disruption, inconvenience and multiple site of care options
		 2 doses of dalbavancin v. 28 doses of vancomycin

- PICC Avoidance
	 Eliminates need for PICC line for post-acute setting IV antibiotic administration
	 Avoids possible complications  associated with PICC lines (i.e., venous thrombus, declotting procedures, readmissions)

Slide 15
ICD-10-PCS

- Create the following new ICD-10-PCS codes to capture the administration of dalbavancin by creating a new, separate qualifier in table 3E0 as is shown below. This option is limited to 3 Peripheral Vein and 4 Central Vein body part values and a percutaneous approach. 

Administration: 3 - Administration

Body System: E - Physiological Systems and Anatomical Regions

Operation: 0 - Introduction; Putting in or on a therapeutic, diagnostic, nutritional, physiological, or prophylactic substance except blood or blood products

Body System/Region: 3 -Peripheral Vein, 4 -Central Vein

Approach: 3 -Percutaneous

Substance: 2 -Anti-infective

Qualifier: 8 -Oxazolidinones, 9 -Other Anti-infective, ADD - R Dalbavancin

- Durata recommends the creation of a new ICD-10-PCS qualifier in order to identify the	administration of dalbavancin for NTAP purposes on inpatient claims
