Slide 1
New ICD-10-PCS Code for the Administration of BLINCYTO (blinatumomab)

- ICD-10-PCS Coordination and Maintenance Committee Meeting

- Dr. Tapan Maniar, Global Development Lead, Amgen Inc.

- March 18, 2015


Slide 2
Agenda

- Unmet Medical Need for the Treatment of Philadelphia-chromosome Negative (Ph-) Relapsed/Refractory (R/R) B-cell Precursor Acute Lymphoblastic Leukemia (ALL)

- BLINCYTO for the Treatment of Ph- R/R B-cell Precursor ALL

- BLINCYTO and International Classification of Diseases, Tenth Revision, Procedure Coding System (ICD-10-PCS) Considerations


Slide 3
BLINCYTO - A Significant Clinical Improvement for Treatment of Ph- R/R B-cell precursor ALL
       
- Significant unmet need to treat the Ph- R/R B-cell precursor ALL patient population - prognosis is poor, and there are no clearly superior treatment regimens

- BLINCYTO - a first-in-class antineoplastic immunotherapy called bi-specific T-cell engagers (BiTE) to treat Ph- R/R B-cell precursor ALL

- Food and Drug Administration (FDA) approval on December 3, 2014

- Applied for New Technology Add-on Payment from the Centers for Medicare & Medicaid Services (CMS) beginning fiscal year (FY) 2016

- Current ICD-10-PCS - no unique mechanism to identify the intravenous administration of BLINCYTO


Slide 4
Unmet Medical Need for R/R ALL Patients With Limited Treatment Options and Poor Prognoses

- ALL is a blood and bone marrow cancer affecting white blood cells
	- ALL occurs when there are malignant transformations of B-cell or T-cell progenitor cells, causing an accumulation of lymphoblasts in the blood, bone marrow, and sometimes throughout the body

- Approximately 6,050 new ALL cases diagnosed in the U.S. each year
	- Approximately 2,400 cases are adults

- Numerous salvage regimens, such as multi-agent chemotherapy regimens, with similar active agents are used to achieve complete remission (CR)
	- No clearly superior regimen

- Allogeneic hematopoietic stem cell transplant (AlloHSCT) is the only potentially curative option, but is typically only successful when patients are in CR; not for patients who are R/R

- Current prognosis is poor
	- 7 percent estimated overall survival at 5 years
	- CR of patients in second salvage is 18 percent

Sources: 1) Mayoclinic.com; 2) Howlader N, et al. SEER Cancer Statistics Review, 1975-2009 (Vintage 2009 Populations), 2012; 3) Fielding et al. Blood, 2007; 4) O'Brien et al. Cancer, 2008


Slide 5
BLINCYTO Received FDA Approval on December 3, 2014

- BLINCYTO is a bispecific CD19-directed CD3 T-cell engager indicated for the treatment of Philadelphia chromosome-negative relapsed or refractory B-cell precursor acute lymphoblastic leukemia

- Orphan designation

- Breakthrough designation

- Priority review

- Accelerated approval
	- Continued approval for this indication may be contingent upon verification of clinical benefit in subsequent trials


Slide 6
BLINCYTO Antineoplastic Immunotherapy: First-in-Class Bispecific T-cell Engager

- Single agent

- Durable and deep (molecular) responses

- Positive benefit:risk profile

- Retains efficacy in difficult to treat populations
	- Early relapse
	- AlloHSCT failure
	- Elderly 
	- Refractory
	- 2nd salvage or greater


Slide 7
BLINCYTO Yielded Better Outcomes Than Historical Comparator and Other Data

- Historical Literature Search
	- Methods: Literature Search
	- Population Achieving CR/Complete Remission with Partial Hematological Recovery of Peripheral Blood Counts (CRh*): 18% to 38.6%
	- Median Relapse-free Survival (RFS): N/A
	- Median Overall Survival (OS): 3.0 to 4.7 months

- Model-Based Meta-Analysis (Study 118427)
	- Methods: Simulation of Control Arm - with Same Patient Characteristics as in Study 103-211
	- Population Achieving CR/CRh*: 12.1% (95% Confidence Interval [CI]: 4.1% to 34%)
	- Median RFS: 4.9 months (95% CI: 2.5 to 9.2)
	- Median OS: 3.9 months (95% CI: 3.0 to 4.7)

- Historical Comparator Data (Study 20120310)
	- Methods: Historical Database Study (Patient-level data)
	- Population Achieving CR/CRh*: 24% (95% CI: 20% to 27%)
	- Median RFS: 5.0 months (95% CI: 1.2 to 6.6)
	- Median OS: 3.3 months (95% CI: 2.8 to 3.6)

- BLINCYTO Pivotal Clinical Trial (Study MT 103-211)
	- Methods: Phase 2 single-arm clinical trial 
	- Population Achieving CR/CRh*: 41.6% (95% CI: 34.4% to 49.1%)
	- Median RFS: 5.9 months (95% CI: 4.8 to 8.3)
	- Median OS: 6.1 months (95% CI: 6.1 to 7.5)

Sources: 1) Gokbuget et al. Blood, 2012; Kantarjian et al. Cancer, 2010; Oriol et al. Haematologica, 2010; O'Brien et al. Cancer, 2008; Thomas et al. Cancer, 1999; 2) Amgen data on file; 3) BLINCYTO U.S. Package Insert


Slide 8
Safety Profile

- Adverse Events (AEs) Regardless of Causality (during treatment until 30 days post-treatment)
	- Adverse events, n(%)* : All Patients (N=189)
		- Worst grade 1 or 2 : 33 (17)
		- Worst grade 3 or 4 : 127 (67)
		- Worst grade 5 (death) : 28 (15)
	- Grade 3 or greater occurred in greater than or equal to 5% of patients
	- *Common Terminology Criteria for Adverse Events (CTCAE) v4.0

- Fatal AEs Regardless of Causality
	- Adverse events, n* : All Patients/Death (N=189/n=28)
		- Infection : 17
		- Disease Progression** : 5
		- Hemorrhage: 2
		- Other : 4
	- *CTCAE v4.0
	- **Some considered possibly related to blinatumomab treatment
	- No patient in remission had fatal adverse events while on BLINCYTO (blinatumomab)

- Cytokine Release Syndrome (CRS) and Neurologic Events Regardless of Causality
	- All Patients (N=189)
		- Nervous system/psychiatric disorders, n(%)*
			- Grade 5 : 0 (0)
			- Grade 4 : 3 (2)
			- Grade 3 : 21 (11)
			- Any Grade (in greater than or equal to 2% of patients) : 98 (52)
		- Incidence of CRS, n(%)*
			- Grade 5 : 0 (0)
			- Grade 4 : 0 (0)
			- Grade 3 : 3 (2)
			- Any Grade (in greater than or equal to 2% of patients) : 24 (12.7)
	- *CTCAE v4.0

Data on this slide is reflective of the Phase 2 study population only (189 patients) and does not include data from the entire safety database (212 patients)
Source: Topp et al. Lancet Oncology, 2014


Slide 9
BLINCYTO Represents a Substantial Clinical Improvement Over Current Chemotherapies
	
- Substantial improvement with single-agent BLINCYTO in OS and CR compared to historical data for multi-agent chemotherapy

- Offers a treatment option for patients that may be unresponsive to available treatments

- Allows patients to bride to alloHSCT, the only potential curative option
	- 39 percent of patients who achieved CR/CRh* went on to alloHSCT

- Effective in patients resistant to standard therapy and in populations with negative prognostic factors

- BLINCYTO has a positive benefit:risk profile for patients that may be suffering from cumulative toxic effects of multiple chemotherapy treatments

- BLINCYTO has a BOXED WARNING in its product label regarding CRS and Neurological Toxicities

Sources: 1) Amgen data on file; 2) BLINCYTO U.S. Package Insert


Slide 10
BLINCYTO is a Continuous Intravenous Infusion Initiated in the Inpatient Setting

- Dosage and Administration 
	- Administered via continuous intravenous infusion into central or peripheral vein
	- Dosage is 28 mcg per day, with the exception of Days 1 through 7 in Cycle 1 at 9 mcg per day
	- Pump must be refilled every 24 to 48 hours

- Treatment Duration
	- A cycle of treatment consists of 4 weeks of continuous intravenous infusion followed by a 2-week treatment-free interval
	- A treatment course consists of up to 2 cycles of BLINCYTO for induction followed by 3 additional cycles for consolidation treatment (up to a total of 5 cycles)

- Setting of Care
	- BLINCYTO treatment initiated in the inpatient setting
		- Some patients transition to outpatient settings of care during a cycle
		- Some patients remain in the inpatient setting for the full cycle
 

Slide 11
New ICD-10-PCS Code for the Administration of BLINCYTO Requested

- Amgen requests to establish new ICD-10-PCS codes through the use of a qualifier so hospitals and payers can identify BLINCYTO administration for the treatment of Ph- R/R B-cell precursor ALL on claims

- Amgen proposes to add new Qualifier value R Blinatumomab to Section 3, Body System E, Operation 0:

Section: 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: 0 - Antineoplastic

Qualifier: 2 - High-dose Interleukin-2, 3 - Low-dose Interleukin-2, 4 - Other Antineoplastic, M - Monoclonal antibody, P - Clofarabine, ADD R BLINATUMOMAB


Slide 12
Rationale to Add Qualifier for Blinatumomab Under the "0 Antineoplastic" Substance Category

- BLINCYTO is an antineoplastic immunotherapy

- Consistent with other ICD-10-CM coding conventions, e.g., Z51.12 Encounter for antineoplastic immunotherapy

- Consistent with pre-existing qualifiers in the Antineoplastic Substance category, e.g., interleukin-2

- Precedent exists for drug-specific qualifiers, e.g., "P Clofarabine"

- Unique qualifier and ICD-10-PCS code necessary to facilitate new technology add-on payment


Slide 13
In Summary

- BLINCYTO - first-in-class antineoplastic immunotherapy to treat an unmet medical need

- Current ICD-10-PCS - no unique mechanism to identify the intravenous administration of BLINCYTO 

- Request to establish new ICD-10-PCS codes to facilitate hospital and payer identification of BLINCYTO administration
	- Required to facilitate inpatient hospital new technology add-on payment

- "0 Antineoplastic" Substance category most appropriate for addition of BLINCYTO qualifier

- Amgen recommends the creation of a new ICD-10-PCS qualifier value R Blinatumomab to support identification of BLINCYTO-specific administrations and facilitate new technology add-on payment adjudication on inpatient claims