Prescribing Information
Logo for ONIVYDE® (irinotecan liposome injection) for treatment of metastatic pancreatic cancerLogo for ONIVYDE® (irinotecan liposome injection) for treatment of metastatic pancreatic cancer

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  • CLINICAL EVIDENCE
  • Primary Efficacy Analysis
Man with metastatic pancreatic cancer painting at an easel with grandson. Safety and effectiveness of ONIVYDE have not been established in pediatric patients. Man with metastatic pancreatic cancer painting at an easel with grandson. Safety and effectiveness of ONIVYDE have not been established in pediatric patients.

What could the possibility
of extended OS mean
for your patients?

FOR JOE,
it could be more
weekend painting lessons
with his grandson

Actor portrayal. Safety and effectiveness
of ONIVYDE have not been established in
pediatric patients.

CLINICALLY SIGNIFICANT OS AND PFS

ONIVYDE + 5-FU/LV increased median overall survival (OS) by approximately 2 months vs 5-FU/LV alone (primary endpoint)1

NAPOLI-1 primary endpoint chart: Median overall survival (OS) for ONIVYDE® (irinotecan liposome injection) + 5-FU/LV vs 5-FU/LV alone NAPOLI-1 primary endpoint chart: Median overall survival (OS) for ONIVYDE® (irinotecan liposome injection) + 5-FU/LV vs 5-FU/LV alone
  • An increased 1-year probability of survival: 24% with ONIVYDE + 5-FU/LV vs 17% with 5-FU/LV alone10

Limitations: The NAPOLI-1 primary analysis included an exploratory analysis for 1-year probability of survival, which should not be interpreted as a treatment difference between arms at 1 year due to potential bias and no formal statistical protection for false positive findings.11

NAPOLI-1 was a global, phase 3, randomized, open-label, multicenter trial in patients (N=417) with metastatic adenocarcinoma of the pancreas whose disease had progressed following gemcitabine-based therapy. Patients were initially randomized to receive ONIVYDE (100 mg/m2 every 3 weeks) or 5-FU/LV (fluorouracil 2000 mg/m2 and leucovorin 200 mg/m2 over 24 hours weekly for 4 weeks, followed by 2 weeks’ rest). After 63 patients were enrolled, a third arm, ONIVYDE (70 mg/m2 every 2 weeks) + 5-FU/LV (fluorouracil 2400 mg/m2 and leucovorin 400 mg/m2 every 2 weeks), was added. Treatment was continued until disease progression or unacceptable toxicity. The primary endpoint, median OS, was assessed with 2 pair-wise comparisons: ONIVYDE (n=151) vs 5-FU/LV (n=149) and ONIVYDE + 5-FU/LV (n=117) vs 5-FU/LV (n=119, post-protocol amendment). There was no improvement in OS for ONIVYDE vs 5-FU/LV (HR=1.00, p=0.97 [2-sided log-rank]). Additional endpoints were PFS and ORR.1,12

ONIVYDE + 5-FU/LV extended median progression-free survival (PFS) vs 5-FU/LV alone (secondary endpoint)1,13

NAPOLI-1 secondary endpoint chart: Median progression-free survival (PFS) for ONIVYDE® (irinotecan liposome injection) + 5-FU/LV vs 5-FU/LV alone NAPOLI-1 secondary endpoint chart: Median progression-free survival (PFS) for ONIVYDE® (irinotecan liposome injection) + 5-FU/LV vs 5-FU/LV alone
  • Confirmed objective response rate (ORR): 7.7% (9/117) with ONIVYDE + 5-FU/LV vs 0.8% (1/119) with 5-FU/LV alone1†

ONIVYDE + 5-FU/LV doubled patients’ progression-free survival1,13

*ONIVYDE monotherapy had no effect on OS.12

†Investigator assessment per RECIST v1.1.12

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IMPORTANT SAFETY INFORMATION AND INDICATION

WARNING: SEVERE NEUTROPENIA AND SEVERE DIARRHEA
  • Fatal neutropenic sepsis occurred in 0.8% of patients receiving ONIVYDE. Severe or life-threatening neutropenic fever or sepsis occurred in 3% and severe or life-threatening neutropenia occurred in 20% of patients receiving ONIVYDE in combination with 5-FU and LV. Withhold ONIVYDE for absolute neutrophil count below 1500/mm3 or neutropenic fever. Monitor blood cell counts periodically during treatment

  • Severe diarrhea occurred in 13% of patients receiving ONIVYDE in combination with 5-FU/LV. Do not administer ONIVYDE to patients with bowel obstruction. Withhold ONIVYDE for diarrhea of Grade 2-4 severity. Administer loperamide for late diarrhea of any severity. Administer atropine, if not contraindicated, for early diarrhea of any severity
INDICATION

ONIVYDE® (irinotecan liposome injection) is indicated, in combination with fluorouracil (5-FU) and leucovorin (LV), for the treatment of patients with metastatic adenocarcinoma of the pancreas after disease progression following gemcitabine-based therapy.

Limitation of Use: ONIVYDE is not indicated as a single agent for the treatment of patients with metastatic adenocarcinoma of the pancreas.

CONTRAINDICATION
  • ONIVYDE is contraindicated in patients who have experienced a severe hypersensitivity reaction to ONIVYDE or irinotecan HCl
WARNINGS AND PRECAUTIONS
  • Severe Neutropenia: See Boxed WARNING. In patients receiving ONIVYDE/5-FU/LV, the incidence of Grade 3/4 neutropenia was higher among Asian (18/33 [55%]) vs White patients (13/73 [18%]). Neutropenic fever/neutropenic sepsis was reported in 6% of Asian vs 1% of White patients
  • Severe Diarrhea: See Boxed WARNING. Severe and life-threatening late-onset (onset >24 hours after chemotherapy [9%]) and early-onset diarrhea (onset ≤24 hours after chemotherapy [3%], sometimes with other symptoms of cholinergic reaction) were observed
  • Interstitial Lung Disease (ILD): Irinotecan HCl can cause severe and fatal ILD. Withhold ONIVYDE in patients with new or progressive dyspnea, cough, and fever, pending diagnostic evaluation. Discontinue ONIVYDE in patients with a confirmed diagnosis of ILD
  • Severe Hypersensitivity Reactions: Irinotecan HCl can cause severe hypersensitivity reactions, including anaphylactic reactions. Permanently discontinue ONIVYDE in patients who experience a severe hypersensitivity reaction
  • Embryo-Fetal Toxicity: ONIVYDE can cause fetal harm when administered to a pregnant woman. Advise females of reproductive potential to use effective contraception during and for 1 month after ONIVYDE treatment
ADVERSE REACTIONS
  • The most common adverse reactions (≥20%) were diarrhea (59%), fatigue/asthenia (56%), vomiting (52%), nausea (51%), decreased appetite (44%), stomatitis (32%), and pyrexia (23%)
  • The most common Grade 3/4 adverse reactions (≥10%) were diarrhea (13%), fatigue/asthenia (21%), and vomiting (11%)
  • Adverse reactions led to permanent discontinuation of ONIVYDE in 11% of patients receiving ONIVYDE/5-FU/LV; The most frequent adverse reactions resulting in discontinuation of ONIVYDE were diarrhea, vomiting, and sepsis
  • Dose reductions of ONIVYDE for adverse reactions occurred in 33% of patients receiving ONIVYDE/5-FU/LV; the most frequent adverse reactions requiring dose reductions were neutropenia, diarrhea, nausea, and anemia
  • ONIVYDE was withheld or delayed for adverse reactions in 62% of patients receiving ONIVYDE/5-FU/LV; the most frequent adverse reactions requiring interruption or delays were neutropenia, diarrhea, fatigue, vomiting, and thrombocytopenia
  • The most common laboratory abnormalities (≥20%) were anemia (97%), lymphopenia (81%), neutropenia (52%), increased ALT (51%), hypoalbuminemia (43%), thrombocytopenia (41%), hypomagnesemia (35%), hypokalemia (32%), hypocalcemia (32%), hypophosphatemia (29%), and hyponatremia (27%)
DRUG INTERACTIONS
  • Avoid the use of strong CYP3A4 inducers, if possible, and substitute non-enzyme inducing therapies ≥2 weeks prior to initiation of ONIVYDE
  • Avoid the use of strong CYP3A4 or UGT1A1 inhibitors, if possible, and discontinue strong CYP3A4 inhibitors ≥1 week prior to starting therapy
USE IN SPECIFIC POPULATIONS
  • Pregnancy and Reproductive Potential: See WARNINGS & PRECAUTIONS. Advise males with female partners of reproductive potential to use condoms during and for 4 months after ONIVYDE treatment
  • Lactation: Advise nursing women not to breastfeed during and for 1 month after ONIVYDE treatment

To report SUSPECTED ADVERSE REACTIONS, contact Ipsen Biopharmaceuticals, Inc. at 1-855-463-5127 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

Please see full Prescribing Information, including Boxed WARNING.

 

References: 1. ONIVYDE® [package insert]. Basking Ridge, NJ. Ipsen Biopharmaceuticals, Inc.; 2017. 2. Ipsen data on file: IQVIA medical claims post-gemcitabine usage analysis, June 2018 – October 2021. 3. Zhang H. Onivyde for the therapy of multiple solid tumors. OncoTargets Ther. 2016;9:3001-3007. 4. Dimou A, Syrigos KN, Saif MW. Overcoming the stromal barrier: technologies to optimize drug delivery in pancreatic cancer. Ther Adv Med Oncol. 2012;4(5):271-279. 5. Drummond DC, Noble CO, Guo Z, Hong K, Park JW, Kirpotin DB. Development of a highly active nanoliposomal irinotecan using a novel intraliposomal stabilization strategy. Cancer Res. 2006;66(6):3271-3277. 6. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Pancreatic Adenocarcinoma V.1.2022. © National Comprehensive Cancer Network, Inc. 2022. All rights reserved. Accessed May 5, 2022. To view the most recent and complete version of the guideline, go online to NCCN.org. 7. Oberstein PE, Olive KP. Pancreatic cancer: why is it so hard to treat? Ther Adv Gastroenterol. 2013;6(4):321-337. 8. Sercombe L, Veerati T, Moheimani F, Wu SY, Sood AK, Hua S. Advances and Challenges of Liposome Assisted Drug Delivery. Front Pharmacol. 2015;6:286. 9. Kalra AV, Kim J, Klinz SG, et al. Preclinical activity of nanoliposomal irinotecan is governed by tumor deposition and intratumor prodrug conversion. Cancer Res. 2014;74(23):7003-7013. 10. Data on file #3. Basking Ridge, NJ. Ipsen Biopharmaceuticals, Inc.; 2015. 11. Wang-Gillam A, Hubner RA, Siveke JT, et al. NAPOLI-1 phase 3 study of liposomal irinotecan in metastatic pancreatic cancer: Final overall survival analysis and characteristics of long-term survivors. Eur J Cancer. 2019;108:78-87. 12. Wang-Gillam A, Li C-P, Bodoky G, et al. Nanoliposomal irinotecan with fluorouracil and folinic acid in metastatic pancreatic cancer after previous gemcitabine-based therapy (NAPOLI-1): a global, randomised, open-label, phase 3 trial. Lancet. 2016;387(10018):545-557. 13. Data on file #1. Basking Ridge, NJ. Ipsen Biopharmaceuticals, Inc.; 2015. 14. Department of Health and Human Services. U.S. Food and Drug Administration. ONIVYDE (irinotecan liposome injection) Approval Letter. NDA 207793. October 22, 2015. Available at: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/207793Orig1s000Approv.pdf. Accessed March 28, 2022. 15. Ipsen data on file: Breakaway Partners dashboard.