EFFICACY & SAFETY

IN FIRST-LINE TREATMENT OF SAA

Rapid response as early as 3 months²

OVERALL RESPONSE RATE AT 3 MONTHS (COHORT 3 + EXTENSION COHORT)²

Double their chances of a complete response by starting in 1L^1-3

COMPLETE RESPONSE RATE AT 6 MONTHS (COHORT 3 + EXTENSION COHORT)¹

• Complete response was defined as hematologic parameters meeting all 3 of the following values on 2 consecutive serial blood count measurements at least 1 week apart: ANC >1000/mcL, platelet count >100,000/mcL, and Hb count >10g/dL¹

OVERALL RESPONSE RATE AT 6 MONTHS (COHORT 3 + EXTENSION COHORT)¹

• Overall response rate was defined as the number of partial responses (blood counts no longer meeting the standard criteria for severe pancytopenia in SAA^†) plus complete responses¹

^†Equivalent to 2 of the following values on 2 consecutive serial blood count measurements at least 1 week apart: ANC >500/mcL, platelet count >20,000/mcL, or reticulocyte count >60,000/mcL.¹

SUSTAINED RESPONSE OFF TREATMENT DEMONSTRATED 18 MONTHS AFTER PATIENTS DISCONTINUED PROMACTA^1,2

• The median duration of response–24.3 months–was consistent for patients achieving a complete response (n=46; 95% CI, 23.0-NE) or an overall response (n=70; 95% CI, 21.4-NE) at any time with PROMACTA + IST (Cohort 3 + extension cohort)^1,2

Study Design

ETB115AUS01T was a single-arm, open-label, sequential cohort trial in patients 2 years of age or older (N=153).¹ All cohorts received h-ATG Days 1 to 4 and CsA for 6 to 24 months.^1,‡ Cohort 3 + extension cohort patients received PROMACTA Day 1 to 6 months (n=92).^1,§ Sixty-six patients were ≥17 years of age and 26 patients were 2 to 16 years of age.¹

^‡Patients in all cohorts received a therapeutic dose of CsA Day 1 to 6 months.¹ Following a protocol amendment, patients who responded at 6 months received a maintenance dose of CsA (2 mg/kg/day) for 18 months after discontinuation of PROMACTA.^1,2 Fifteen responders in Cohort 2 (n=27/31) and 67 responders in Cohort 3 + extension cohort (n=69/87) received maintenance CsA.^1,2
§Of these patients, 5 were not included in analyses of hematologic response at Month 6, as they had neither reached the 6-month assessment nor withdrawn earlier.¹

ADVERSE REACTIONS IN SAA IN FIRST LINE (COHORT 3 + EXTENSION COHORT)¹

^a The only serious adverse drug reactions experienced by ≥10% of pediatric patients were rash and upper respiratory tract infection (12% in patients age 2 to 16 years compared with 5% in patients 17 years of age and older).

• Grade 3 and grade 4 liver function laboratory abnormalities were 15% and 2% for AST, 26% and 4% for ALT, and 12% and 1% for bilirubin, respectively

• Patients had bone marrow aspirates evaluated for cytogenetic abnormalities. Seven patients in Cohort 3 + extension cohort had a new cytogenetic abnormality reported, of which 4 had the loss of chromosome 7

IN RELAPSED/REFRACTORY SAA

Make a trilineage difference: PROMACTA monotherapy provided a sustained multilineage response¹

HEMATOPOIESIS MAINTAINED AFTER DISCONTINUATION^1,4

• A multilineage response is defined as an increase in production in ≥2 of the following hematologic markers: Platelets, white blood cells, and red blood cells^4,5

Study Design

ELT112523 was a prospective, open-label, nonrandomized, single-arm, dose-modification, investigator-sponsored study conducted by the National Institutes of Health to assess the safety and efficacy of PROMACTA in patients with SAA and IST-refractory thrombocytopenia (N=43).^1,4,5

The primary end point was hematologic response at Week 12 or Week 16, defined by meeting 1 or more of the following criteria^1,5:

• Platelet count increase to 20,000/mcL above baseline or stable platelet counts with transfusion independence for a minimum of 8 weeks

• Hb count increase >1.5 g/dL for patients with pretreatment Hb count <9 g/dL or a reduction in ≥4 units of red blood cell transfusions for 8 consecutive weeks

• ANC increase of 100% or >500/mcL

Patients who responded in the initial phase were eligible to continue therapy in an extension phase.^1,4

Patients had a median age of 45 years and either had an insufficient response to at least 1 prior course of IST or were relapsed/refractory and had responded to at least 1 prior cycle of IST but were refractory to the most recent course of IST.^1,5

ADVERSE REACTIONS IN THE RELAPSED/REFRACTORY POPULATION (≥10%)¹

• If new cytogenetic abnormalities are observed, consider discontinuation of PROMACTA

• Patients had bone marrow aspirates evaluated for cytogenetic abnormalities

• Eight patients had a new cytogenetic abnormality reported while on therapy, including 5 patients who had complex changes in chromosome 7

DOSING & ADMINISTRATION

FOR ALL PROMACTA PATIENTS

• PROMACTA can be taken without food or with food low in calcium (≤50 mg)¹

• PROMACTA should be taken at least 2 hours before or 4 hours after medications such as antacids and mineral supplements or foods high in calcium¹

• PROMACTA can be taken any time of day, at the same time each day¹

Available Formulations

Dosing flexibility, even for patients who have difficulty swallowing a pill¹

IN FIRST-LINE TREATMENT OF SAA

Initiate PROMACTA concurrently with h-ATG + CsA¹

• Do not exceed the recommended initial dose of PROMACTA

• A single treatment course of h-ATG should be administered intravenously at a dose of 40 mg/kg/day for 4 consecutive days starting Day 1¹

• CsA should be administered at a dose of 6 mg/kg/day (12 mg/kg/day for children under 12 years of age) from Day 1 for 6 months¹

FOR PATIENTS WITH RELAPSED/REFRACTORY SAA

Initiate as monotherapy¹

1L, first line; ALT, alanine aminotransferase; ANC, absolute neutrophil count; AST, aspartate aminotransferase; CsA, cyclosporine A; h-ATG, horse antithymocyte globulin; Hb, hemoglobin; IST, immunosuppressive therapy; NE, not estimable; SAA, severe aplastic anemia.