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IDHIFA Clinical Trial Design

FDA approval of IDHIFA was based on results from
THE FIRST PIVOTAL TRIAL EXCLUSIVELY IN R/R AML WITH AN IDH2 MUTATION

IDHIFA was studied in an open-label, single-arm, multicenter, clinical trial of patients with R/R AML and an IDH2 mutation who were assigned a starting dose of 100 mg daily until disease progression or unacceptable toxicity. Dose reductions were allowed to manage adverse events.

214
patients in the efficacy analysis
199
patients in the safety analysis
the first pivotal trial exclusively in relapsed refractory aml with an idh2 mutation

For patients in the efficacy analysis, IDH2 mutations were either prospectively identified or retrospectively confirmed by the Abbott RealTime™ IDH2 assay.

  • Of the patients enrolled and treated, 93% (199/214) had IDH2 mutations detected by the Abbott RealTime™ IDH2 assay, and had R/R status confirmed by FDA. Therefore, the 199 patients were included in the efficacy analysis1
idhifa efficacy

Efficacy was established on the basis of:

  • Rate of complete response (CR): defined as <5% of blasts in the bone marrow, no evidence of disease, and full recovery of peripheral blood counts (platelets >100,000/μL and absolute neutrophil counts [ANC] >1,000/μL)
  • Rate of complete response with hematologic recovery (CRh): defined as CR requirement for blast count, no evidence of disease, but only partial recovery of peripheral blood counts (platelets >50,000/μL and ANC >500/μL)
  • Duration of response (DOR): defined as time since first response of CR or CRh to relapse or death, whichever is earlier
  • Rate of conversion from transfusion dependence to transfusion independence*

The median follow-up was 6.6 months (range, 0.4 to 27.7).

*Patients were defined as transfusion independent if they received no RBC or platelet transfusions within any 56-day post-baseline period.

IDHIFA CLINICAL BROCHURE

Selected Baseline Characteristics

THE TRIAL INCLUDED A DIFFICULT-TO-TREAT PATIENT POPULATION

SELECTED BASELINE CHARACTERISTICS

Demographic and disease characteristics
R/R AML, N=199 (%)

100-mg daily dose

Median age in years
68 (range, 19-100)
Median time from initial AML diagnosis in months (172 patients)11.3 (range, 1.2-129.1)
ECOG PSa
046 (23)
1124 (62)
228 (14)
Relapsed AML95 (48)
Refractory AML104 (52)
IDH2 mutationb
R140155 (78)
R17244 (22)
Prior stem cell transplantation for AML25 (13)
Cytogenetic risk status
Intermediate98 (49)
Poor54 (27)
Missing/failure47 (24)
Transfusion dependent at baselinec157 (79)
Number of prior anticancer regimensd
189 (45)
264 (32)
≥346 (23)
Median number of prior therapies2 (range, 1-6)

a1 patient had missing baseline ECOG PS.

b For 3 patients with different mutations detected in bone marrow compared to blood, the result of blood is reported.

c Patients were defined as transfusion dependent at baseline if they received any RBC or platelet transfusions within the 8-week baseline period.

d Includes intensive and/or nonintensive therapies.

ECOG PS, Eastern Cooperative Oncology Group performance status.

ADDITIONAL BASELINE HEMATOLOGIC PARAMETERS1

Hematologic parameterMedian (range)
Bone marrow blast (n=194)49.5 (range, 0.0-98.0)
ANC counts (n=196)0.39 (range, 0.0-18.0)
Hemoglobin concentration (n=198)91.0 (range, 69.0-156.0)
Platelet counts (n=198)37.0 (range, 1.0-1288.0)

Baseline measurements not available for all patients in cycle 1.

Response Rates

In this challenging clinical setting,
IDHIFA ACHIEVED DURABLE AND CLINICALLY MEANINGFUL RESPONSES

RATE OF COMPLETE RESPONSE (CR) AND CR WITH PARTIAL HEMATOLOGIC RECOVERY (CRh)

CR/CRh 23%
n=46/199
(95% CI, 18%-30%)
CR 19%a
n=37/199
(95% CI, 13%-25%)
CRh 4%b
n=9/199
(95% CI, 2%-8%)

MEDIAN DURATION OF CR/CRhc

8.2
months
n=46/199
Patients
achieving CR/CR
h
(95% CI, 4.3-19.4)
8.2
months
n=37/199
Patients
achieving CR
(95% CI, 4.7-19.4)
9.6
months
n=9/199
Patients
achieving CR
h
(95% CI, 0.7-NA)

a <5% of blasts in the bone marrow, no evidence of disease, and full recovery of peripheral blood counts (platelets >100,000/μL and ANC >1,000/μL).

b <5% of blasts in the bone marrow, no evidence of disease, and partial recovery of peripheral blood counts (platelets >50,000/μL and ANC >500/μL).

c Time since first response of CR or CRh to relapse or death, whichever is earlier.

CI, confidence interval; NA, not available.


ADDITIONAL OUTCOMES FOR PATIENTS WITH R/R AML AND AN IDH2 MUTATION

BEST OBJECTIVE RESPONSE1

Figure depicts the FDA-adjudicated CR/CRh rates and other parameters retrospectively determined by the sponsor using the pivotal data set (N=199).

ORR 33%a
n=65/199
(95% CI, 26%-40%)
CR 19%
n=37/199
(95% CI, 13%-25%)
MLFS 8%
n=15/199

Overall response rate (ORR) is defined as CR + CRh + PR + MLFS.



47%

(n=94/199)

STABLE DISEASE

12%

(n=23/199)

PROGRESSIVE DISEASE

1%

(n=1/199)

NOT EVALUABLE



a Percentages are based on the number of subjects in each group.

MLFS, morphologic leukemia-free state for subjects with AML; PR, partial responses.

WITH IDHIFA, RESPONSES DEEPENED OVER TIME FOR SOME PATIENTS ACHIEVING CR/CRh

MEDIAN TIME TO FIRST AND BEST RESPONSE

PATIENTS
ACHIEVING CR/CRh
n=46/199
Median time to
first response
1.9 mo
(range, 0.5-7.5)
Median time to best
response of CR/CRh
3.7 mo
(range, 0.6-11.2)
6.0 mo
85% OF PATIENTS
who achieved a best response of CR/CRh did so by the end of month 6
(n=39/46)

IDHIFA works differently—treat for a minimum of 6 months to allow time for clinical response in patients without disease progression or unacceptable toxicity

Transfusion Independence

ACHIEVING TRANSFUSION INDEPENDENCE IS CLINICALLY MEANINGFUL

34%

(n=53/157)

34% of patients on IDHIFA who were RBC and/or platelet transfusion dependent at baseline achieved transfusion independence during any 56-day post-baseline period.*

  • Of these 53 patients, 27 had not achieved a CR/CRh at the time of the follow-up1
Of the 42 patients who were independent of both RBC and platelet transfusions at baseline, 32 (76%) remained transfusion independent during any 56-day post-baseline period.

43% of patients (85/199) on IDHIFA became or remained transfusion independent during any 56-day post-baseline period

*Patients were defined as transfusion independent if they received no RBC or platelet transfusions within any 56-day post-baseline period.

ADDITIONAL DATA FOR TRANSFUSION STATUS IN PATIENTS WITH R/R AML AND AN IDH2 MUTATION1

TRANSFUSION STATUS BY RESPONSE TYPE (N=199)

Post-baseline TIPost-baseline TD
CR/CRh (n=46)
RBC or platelet TD at baseline263
RBC or platelet TI at baseline161
Total424
NON-CR/CRh (n=153)
RBC or platelet TD at baseline27101
RBC or platelet TI at baseline169
Total43110
All (N=199)
RBC or platelet TD at baseline53104
RBC or platelet TI at baseline3210
Total85114

TD, transfusion dependent; TI, transfusion independent.

Reference:

  1. Data on file, Celgene Corporation. Summit, New Jersey.

Indication

IDHIFA® (enasidenib) is indicated for the treatment of adult patients with relapsed or refractory (R/R) acute myeloid leukemia (AML) with an isocitrate dehydrogenase-2 (IDH2) mutation as detected by an FDA-approved test.

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Important Safety Information

WARNING: DIFFERENTIATION SYNDROME

Patients treated with IDHIFA have experienced symptoms of differentiation syndrome, which can be fatal if not treated. Symptoms may include fever, dyspnea, acute respiratory distress, pulmonary infiltrates, pleural or pericardial effusions, rapid weight gain or peripheral edema, lymphadenopathy, bone pain, and hepatic, renal, or multi-organ dysfunction. If differentiation syndrome is suspected, initiate corticosteroid therapy and hemodynamic monitoring until symptom resolution.

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WARNINGS AND PRECAUTIONS

Differentiation Syndrome: See Boxed WARNING. In the clinical trial, 14% of patients treated with IDHIFA experienced differentiation syndrome, which may be life-threatening or fatal if not treated. Differentiation syndrome has been observed with and without concomitant hyperleukocytosis, as early as 10 days and at up to 5 months after IDHIFA initiation. Symptoms in patients treated with IDHIFA included acute respiratory distress represented by dyspnea and/or hypoxia and need for supplemental oxygen; pulmonary infiltrates and pleural effusion; renal impairment; fever; lymphadenopathy; bone pain; peripheral edema with rapid weight gain; and pericardial effusion. Hepatic, renal, and multi-organ dysfunction have also been observed. If differentiation syndrome is suspected, initiate systemic corticosteroids and hemodynamic monitoring until improvement. Taper corticosteroids only after resolution of symptoms. Differentiation syndrome symptoms may recur with premature discontinuation of corticosteroids. If severe pulmonary symptoms requiring intubation or ventilator support and/or renal dysfunction persist for more than 48 hours after initiation of corticosteroids, interrupt IDHIFA until signs and symptoms are no longer severe. Hospitalization for close observation and monitoring of patients with pulmonary and/or renal manifestation is recommended.

Embryo-Fetal Toxicity: Based on animal embryo-fetal toxicity studies, IDHIFA can cause embryo-fetal harm when administered to a pregnant woman. Advise females of reproductive potential and males with female partners of reproductive potential to use effective contraception during treatment with IDHIFA and for at least 1 month after the last dose. Pregnant women, patients becoming pregnant while receiving IDHIFA, or male patients with pregnant female partners should be apprised of the potential risk to the fetus.

ADVERSE REACTIONS

  • The most common adverse reactions (≥20%) included total bilirubin increased (81%), calcium decreased (74%), nausea (50%), diarrhea (43%), potassium decreased (41%), vomiting (34%), decreased appetite (34%), and phosphorus decreased (27%)
  • The most frequently reported ≥Grade 3 adverse reactions (≥5%) included total bilirubin increased (15%), potassium decreased (15%), phosphorus decreased (8%), calcium decreased (8%), diarrhea (8%), differentiation syndrome (7%), non-infectious leukocytosis (6%), tumor lysis syndrome (6%), and nausea (5%)
  • Serious adverse reactions were reported in 77.1% of patients. The most frequent serious adverse reactions (≥2%) were leukocytosis (10%), diarrhea (6%), nausea (5%), vomiting (3%), decreased appetite (3%), tumor lysis syndrome (5%), and differentiation syndrome (8%). Differentiation syndrome events characterized as serious included pyrexia, renal failure acute, hypoxia, respiratory failure, and multi-organ failure

LACTATION

Many drugs are excreted in human milk and because of the potential for adverse reactions in breastfed infants, advise women not to breastfeed during treatment with IDHIFA and for at least 1 month after the last dose.

Please see full Prescribing Information, including Boxed WARNING.

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Celgene Commercial Co-pay Program Terms and Conditions

Eligibility

Patients must meet the following criteria to enroll:

  • Covered by commercial or private insurance
  • Reside in the United States or US territory
  • Not participating in a federal or state-funded healthcare program, including, but not limited to, Medicare (Parts B, C, and D) or Medicaid, Medigap, CHAMPUS, VA, DOD, or Tricare
  • Gross annual household income must not exceed $100,000
    • Gross household income is the total income before income tax deductions from all people living in your household. Gross income refers not only to the salaries and benefits received, but also to receipts from any personal business, investments, dividends, and other income

Program Benefits

  • For Celgene oral hematology products, Celgene provides assistance to reduce the co-pay of eligible patients to $25 per prescription with a maximum benefit of $10,000 per enrollment period
  • For Celgene IV products, the Program will cover the co-pay for each prescription of a Celgene product up to a maximum of $10,000 per enrollment period
    • In order to receive the Program benefits for a Celgene IV product, patients or their providers must submit an Explanation of Benefits (EOB) form
  • Patients are responsible for any costs that exceed the Program’s $10,000 maximum
  • The Program will not cover, and shall not be applied toward, the cost of any dosing procedure, any other healthcare provider service or supply charges or other treatment costs, or any costs associated with a hospital stay

Program Timing

  • If eligible, patients will be enrolled from the date of enrollment through the end of the then current calendar year

Additional Terms and Conditions of the Celgene Commercial Co-pay Programs

  • Patients, pharmacists, and healthcare providers must not seek reimbursement from health insurance or any third party for any part of the benefit received by the patient through this Program. Patients must not seek reimbursement from any health savings, flexible spending, or other healthcare reimbursement accounts for the amount of assistance received from the Program
  • Acceptance of this offer confirms that this offer is consistent with your insurance and that you will report the value of the co-pay assistance you receive as may be required by your insurance provider
  • Only valid in the United States and US territories; this offer is void where prohibited by law, taxed or restricted. Absent a change in Massachusetts law, effective July 1, 2019, Massachusetts residents will no longer be eligible to participate in this Program
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  • The Program cannot be combined with any other coupon, rebate, voucher, free trial, or similar offer
  • The Program is not insurance
  • Celgene reserves the right to rescind, revoke, or amend this Program at any time without notice

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