IPSS, International Prognostic Scoring System; qd, once daily.

The recommended daily dose is 400 mg; therefore, only the 400‑mg arm will be shown relative to placebo

Full baseline characteristics

^aAs measured by MRI or CT.

Additional trial information

Select inclusion criteria

A diagnosis of intermediate-2 or high-risk myelofibrosis, post-polycythemia vera myelofibrosis, or post-essential thrombocythemia myelofibrosis with splenomegaly.

Study endpoints

PRIMARY ENDPOINT

The proportion of patients achieving greater than or equal to a 35% reduction from baseline in spleen volume at the end of cycle 6 as measured by magnetic resonance imaging (MRI) or computed tomography (CT) with a scan 4 weeks later.

SECONDARY ENDPOINT

Secondary endpoints included the proportion of patients with a 50% or greater reduction in Total Symptom Score (TSS) from baseline to the end of cycle 6 as measured by the modified Myelofibrosis Symptom Assessment Form (MFSAF) v2.0 diary.

Treatment period

Patients continued to receive INREBIC^® as long as they were benefiting (defined as having had a complete or partial remission, clinical improvement, or stable disease) and had not experienced progressive disease/relapse (as defined by the modified IWG-MRT criteria) or unacceptable toxicity requiring discontinuation of INREBIC^®.

IWG-MRT, International Working Group–Myeloproliferative Neoplasms Research and Treatment.

Percent of Patients with SVR ≥35% At the end of cycle 6 with a scan 4 weeks later

P<0.0001

Based on Kaplan-Meier estimates, the median duration of spleen response for the INREBIC^® 400-mg group was 18.2 months

Percent Change in Spleen Volume at the end of cycle 6 For Each Patient

^aSubjects with available percent change in spleen volume at the end of cycle 6.

Symptom reduction with INREBIC^®

Percent of Patients with ≥50% Reduction in TSS at the end of cycle 6

P<0.0001

Percent Change in TSS At the End of Cycle 6 for each patient

^aSubjects with available percent change in TSS at the end of cycle 6 as measured by the modified MFSAF v2.0 diary. The modified MFSAF v2.0 is a patient diary capturing the 6 core symptoms of MF: night sweats, itching, abdominal discomfort, early satiety, pain under ribs on left side, and bone or muscle pain.

Reduction in individual symptoms

Proportion of Patients Achieving ≥50% Reduction in individual symptom scores at the end of cycle 6 WITH NONZERO BASELINE SCORES^a

^aAs measured by the modified MFSAF v2.0 diary.

INREBIC^® in patients previously treated with ruxolitinib

Study design and select patient characteristics

• Single-arm, open-label, phase-2 study in 97 primary or secondary myelofibrosis patients resistant or intolerant to ruxolitinib per investigator assessment

• The primary endpoint was the proportion of patients achieving ≥35% spleen volume reduction at the end of cycle 6 as measured by MRI or CT

• Median exposure to ruxolitinib prior to enrollment in study was 10.7 months

• Median exposure of INREBIC^® during enrollment in study was 24 weeks (range 0.7-79.4 weeks)

Spleen and symptom response of INREBIC^®

The original JAKARTA2 study analysis included the per-protocol population and used last-observation-carried-forward (LOCF) analysis method for spleen volume. The LOCF method allowed for the last spleen volume assessment to be “carried forward” (imputed) for patients missing end-of-cycle-6 assessments. The following reanalysis included the all-enrolled population (ITT) and the LOCF method was not employed. As such, missing data were not imputed for assessments of spleen volume, and patients missing assessments at the end of cycle 6 were considered nonresponders.

Adverse reactions with INREBIC^® in patients previously treated with ruxolitinib

Hematologic Adverse Reactions (ITT)

^aPresented values are worse-grade values regardless of baseline.

Nonhematologic ADVERSE REACTIONS REPORTED (ITT)

ALT, alanine aminotransferase; AST, aspartate aminotransferase.

^aIncludes cystitis.

^bPresented values are worse-grade values regardless of baseline.

^cOf 96 evaluable patients.

1. Assess before starting

• Assess thiamine levels. Do not start INREBIC^® in patients with thiamine deficiency; replete thiamine prior to treatment initiation and during treatment if thiamine levels are low

• Obtain the following blood tests prior to starting treatment with INREBIC^®, periodically during treatment, and as clinically indicated: thiamine (vitamin B1) level, complete blood count with platelets, creatinine and BUN, hepatic panel, and amylase and lipase

• Patients who are on treatment with ruxolitinib before the initiation of INREBIC^® must taper and discontinue according to the ruxolitinib prescribing information

• Avoid use of INREBIC^® with strong and moderate CYP3A4 inducers, with dual CYP3A4 and CYP2C19 inhibitors, and in patients with severe hepatic impairment

2. Administer the right starting dose

• The recommended dosage of INREBIC^® is 400 mg taken orally once daily for patients with a baseline platelet count of ≥50 x 10⁹/L

• Reduce the INREBIC^® dose to 200 mg once daily for patients using concomitant strong CYP3A4 inhibitors

• Reduce the INREBIC^® dose to 200 mg once daily in patients with severe renal impairment (creatinine clearance [CLcr] 15 mL/min to 29 mL/min)

3. Support patients on INREBIC^®

• If encephalopathy is suspected, immediately discontinue treatment with INREBIC^® and initiate parenteral thiamine treatment. Monitor until symptoms resolve or improve and thiamine levels normalize

• The median time to onset of any grade nausea, vomiting, and diarrhea was 1 day, with 75% of cases occurring within 2 weeks of treatment

• Treat diarrhea with antidiarrheal medications promptly at the first onset of symptoms

• Consider providing appropriate prophylactic antiemetic therapy (eg, 5-HT3 receptor antagonists) during INREBIC^® treatment

• INREBIC^® may be taken with or without food. Administration with a high-fat meal may reduce the incidence of nausea and vomiting

BUN, blood urea nitrogen.

• Serious adverse reactions occurred in 21% of patients

  • Serious adverse reactions that occurred in ≥2% of patients included cardiac failure (5%) and anemia (2%). Fatal adverse reactions of cardiogenic shock occurred in 1% of patients receiving INREBIC^®

• Permanent discontinuation of treatment due to anemia occurred in 1% of patients receiving INREBIC^®

• Permanent discontinuation of treatment due to thrombocytopenia occurred in 2.1% of patients receiving INREBIC^®

Selected Laboratory Abnormalities that have worsened from baseline (≥20%) in Patients Receiving Inrebic^®a

^aWith a difference between arms of >10% when compared to placebo in JAKARTA during randomized treatment.

Most common adverse reactions with INREBIC^®

Management of gastrointestinal adverse reactions

• Consider providing appropriate prophylactic antiemetic therapy (eg, 5-HT3 receptor antagonists) during INREBIC^® treatment

• Treat diarrhea with antidiarrheal medications promptly at the first onset of symptoms

• INREBIC^® may be taken with or without food. Administration with a high-fat meal may reduce the incidence of nausea and vomiting

Selected Adverse Reactions Reported in Patients on INREBIC^®

^aCommon Terminology Criteria for Adverse Events (CTCAE) version 4.03.

^bOnly 1 grade 4 event (anemia).

^cIncludes cystitis.

^dSelected laboratory abnormalities that have worsened from baseline (≥20%) in patients receiving INREBIC^® with a difference between arms of >10% when compared to placebo in JAKARTA during randomized treatment.

Management of encephalopathy, including WE

Assess at treatment initiation

• Assess thiamine levels prior to starting INREBIC^®

• Do not start INREBIC^® in patients with thiamine deficiency

Monitor during treatment

• Assess thiamine levels periodically during treatment and as clinically indicated

• Monitor for signs and symptoms of WE, which may include ataxia, mental status changes, and ophthalmoplegia (eg, nystagmus, diplopia)

Intervene immediately if thiamine deficient or if encephalopathy is suspected

• Do not start INREBIC^® in patients with thiamine deficiency; replete thiamine prior to treatment initiation and during treatment if thiamine levels are low

• If encephalopathy is suspected, immediately discontinue treatment with INREBIC^® and initiate parenteral thiamine treatment

• Monitor until symptoms resolve or improve and thiamine levels normalize

INREBIC^® is available through the contracted specialty pharmacies or through authorized distributors for in-office dispensing by community physicians, hospitals, institutions, Veterans Affairs, and Department of Defense.

Please download the brochure below to find the listing of contracted specialty pharmacies and authorized distributors.

How to Access INREBIC^® Brochure

INREBIC^® product information

How supplied

• INREBIC^® 100 mg capsules are supplied in bottles of 120 count each

Storage

• Store below 86°F (30°C)

Commonly used ICD-10 codes*

• D47.4 (Osteomyelofibrosis)
• D75.81 (Myelofibrosis)

^*When selecting diagnosis codes, providers should consult a current ICD-10-CM manual and always select the most appropriate diagnosis code(s) with the highest level of detail to describe a patient’s actual condition.

Celgene Patient Support^®

A single source for access support

Celgene Patient Support^® provides

• A single Specialist assigned to help patients in your geographic area

• Assistance with understanding patient insurance coverage for INREBIC^®

• Information about financial assistance for INREBIC^®

Financial assistance

Depending on a patient’s insurance situation, there are programs and organizations that may help pay for INREBIC^®.

Celgene Commercial Co-pay Program
For eligible patients with commercial or private insurance (including healthcare exchanges),^† co-pay responsibility for INREBIC^® is reduced to $25 (subject to annual benefit limit).

Celgene Patient Assistance Program (PAP)
For qualified patients who are uninsured or underinsured, INREBIC^® may be available at no cost.^‡

Independent third-party organizations
For patients who are unable to afford their medication (including patients with Medicare, Medicaid, or other government-sponsored insurance),^§ independent third-party organizations may be able to help.

Insurance-related assistance

Our Specialists are available to assist with each of the following steps in the insurance approval process for INREBIC^®‖:

• Benefits investigation

• Prior authorization assistance/precertification assistance^¶

• Appeals assistance^¶

Enrolling in Celgene Patient Support^®

There are 3 simple ways to enroll in Celgene Patient Support^®

Enroll online at
www.celgenepatientsupport.com.

Call us at 1-800-931-8691,
Monday–Friday, 8 AM–8 PM ET
(translation services available).

E-mail a completed enrollment form to
patientsupport@celgene.com
or fax 1-800-822-2496.