A couple affected by metastatic pancreatic cancer sitting on a porch having coffee

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

FOR CAROL AND BOB,
it could be more morning
coffees together

Actor portrayal

EFFICACY AND SAFETY STUDIED IN A GLOBAL PHASE 3 CLINICAL TRIAL^1,12

NAPOLI-1: a large, phase 3 trial in patients with mPDAC with disease progression after gemcitabine-based therapy^12,13

NAPOLI-1 study design: a large, phase 3, open-label clinical trial of patients randomized across 3 arms: ONIVYDE® (irinotecan liposome injection) + 5-FU/LV, 5-FU/LV alone, and ONIVYDE® (irinotecan liposome injection) alone

Treatment continued until disease progression or unacceptable toxicity¹

Primary endpoint: OS¹

OS was evaluated using 2 pair-wise comparisons: ONIVYDE® (irinotecan liposome injection) vs 5-FU/LV and ONIVYDE + 5-FU/LV vs 5-FU/LV
The comparisons between the ONIVYDE + 5-FU/LV and the 5-FU/LV arms are limited to patients enrolled in the 5-FU/LV arm after the protocol amendment (n=119)

Secondary endpoints: PFS, ORR, and safety^1,13

Tumor status assessments were conducted at baseline and every 6 weeks thereafter or sooner if investigator suspected disease progression

ONIVYDE + 5-FU/LV is the FIRST AND ONLY FDA-approved regimen for mPDAC post-gemcitabine¹

ONIVYDE® (irinotecan liposome injection), FDA approved in 2015, is the #1 prescribed and fastest growing second-line regimen for metastatic pancreatic adenocarcinoma after progression on gemcitabine

*Study was amended to add the ONIVYDE + 5-FU/LV arm once safety data on the combination became available; 63 patients already had been enrolled in the original 2-arm study at the time of amendment.^1,12

^†The disease must have progressed after previous gemcitabine-based therapy given in a neoadjuvant, adjuvant (only if distant metastases occurred within 6 months of completing adjuvant therapy), locally advanced, or metastatic setting.¹²

^‡Based on metastatic pancreatic cancer patients who have had at least 3 cycles of a gemcitabine-based regimen and did not have pancreatic cancer-related activity for 60 days prior to beginning an ONIVYDE treatment regimen. Based on data from Q4 2016 through Q3 2021.²

2L=second line.

SAFETY DATA

INDICATIONS

ONIVYDE® (irinotecan liposome injection) is indicated, in combination with oxaliplatin, fluorouracil, and leucovorin, for the first-line treatment of adult patients with metastatic pancreatic adenocarcinoma.
ONIVYDE is indicated, in combination with fluorouracil and leucovorin, for the treatment of adult patients with metastatic pancreatic adenocarcinoma after disease progression following gemcitabine-based therapy.

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

IMPORTANT SAFETY INFORMATION

WARNING: SEVERE NEUTROPENIA AND SEVERE DIARRHEA

Neutropenia

Severe and life-threatening neutropenia, including fatal neutropenic sepsis and fatal neutropenic fever, has occurred in patients receiving ONIVYDE in combination with oxaliplatin, fluorouracil, and leucovorin and in combination with fluorouracil and leucovorin. Withhold ONIVYDE for absolute neutrophil count below 1500/mm³ or neutropenic fever. Monitor blood cell counts periodically during treatment.

Diarrhea

Severe and life-threatening diarrhea has occurred in patients receiving ONIVYDE in combination with oxaliplatin, fluorouracil, and leucovorin and in combination with fluorouracil and leucovorin. 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.

CONTRAINDICATIONS

ONIVYDE is contraindicated in patients who have experienced a severe hypersensitivity reaction or anaphylaxis to ONIVYDE or irinotecan HCl.

WARNINGS AND PRECAUTIONS

Severe Neutropenia: ONIVYDE can cause severe or life-threatening neutropenia and fatal neutropenic sepsis. In NAPOLI 3, Grade 3 and 4 neutropenia occurred in 26% of patients receiving ONIVYDE in combination with oxaliplatin, ﬂuorouracil, and leucovorin (NALIRIFOX) and fatal neutropenic fever in 0.3% of patients. In NAPOLI 3, the incidence of Grade 3 or 4 neutropenia was similar among Asian patients [6 of 20 (30%)] compared to White patients [76 of 289 (26%)]. Neutropenic fever/neutropenic sepsis was reported in 5% of Asian patients (1 of 20) compared to 2.3% of White patients (7 of 306). In NAPOLI-1, Grade 3 and 4 neutropenia occurred in 20% of patients receiving ONIVYDE in combination with ﬂuorouracil and leucovorin (ONIVYDE/FU/LV). Neutropenic sepsis occurred in 3% and fatal neutropenic sepsis in 0.8%. In NAPOLI-1, the incidence of Grade 3 or 4 neutropenia was higher among Asian patients [18 of 33 (55%)] compared to White patients [13 of 73 (18%)]. Neutropenic fever/neutropenic sepsis was reported in 6% of Asian patients compared to 1% of White patients.

Monitor complete blood cell counts on Days 1 and 8 of every cycle and more frequently if clinically indicated. Withhold ONIVYDE if the absolute neutrophil count (ANC) is below 1500/mm³ or if neutropenic fever occurs. Resume ONIVYDE when the ANC is 1500/mm³ or above. Reduce ONIVYDE dose for Grade 3-4 neutropenia or neutropenic fever following recovery in subsequent cycles.

Severe Diarrhea: In NAPOLI 3, Grade 3 and 4 diarrhea (early-onset [within 24 hours of chemotherapy] and late-onset [more than 24 hours following chemotherapy]) occurred in 20% receiving NALIRIFOX. In NAPOLI-1, Grade 3 or 4 diarrhea occurred in 13% receiving ONIVYDE/FU/LV. The incidence of Grade 3 or 4 late-onset diarrhea was 9% in patients receiving ONIVYDE/FU/LV. The incidence of Grade 3 or 4 early-onset diarrhea was 3% in patients receiving ONIVYDE/FU/LV.

To reduce the risk of severe diarrhea, patients should stop lactose-containing products, eat a low-fat diet, and maintain hydration during treatment with ONIVYDE. Withhold ONIVYDE for Grade 2-4 diarrhea. Local institutional guidelines should be followed for the treatment of diarrhea that does not improve within 48 hours and may include the addition of diphenoxylate hydrochloride plus atropine sulfate or octreotide. Following recovery to Grade 1 diarrhea, resume ONIVYDE at a reduced dose.

Interstitial Lung Disease (ILD): ONIVYDE can cause severe and fatal ILD. Postmarketing cases of severe and fatal ILD have been reported with ONIVYDE. Risk factors include pre-existing lung disease, use of pneumotoxic medicinal products, colony stimulating factors or having previously received radiation therapy. Patients with risk factors should be closely monitored for respiratory symptoms before and during ONIVYDE therapy. 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 Reaction: Irinotecan, including ONIVYDE, can cause severe hypersensitivity reactions, including anaphylactic reactions. Permanently discontinue ONIVYDE in patients who experience a severe hypersensitivity reaction.

Embryo-Fetal Toxicity: Based on animal data with irinotecan HCl and the mechanism of action of ONIVYDE, ONIVYDE can cause fetal harm when administered to a pregnant woman. Advise pregnant women of the potential risk to a fetus. Advise females of reproductive potential to use effective contraception during and for 7 months after the last dose of ONIVYDE treatment.

ADVERSE REACTIONS FOR NALIRIFOX

The most common adverse reactions (≥20%) of NALIRIFOX were diarrhea (72%), fatigue (62%), nausea (59%), vomiting (40%), decreased appetite (37%), abdominal pain (35%), mucosal inflammation (28%), constipation (25%), and weight decreased (22%).
Permanent discontinuation of ONIVYDE due to an adverse reaction occurred in 17% of patients. Adverse reactions that resulted in permanent discontinuation of ONIVYDE in ≥1% of patients included neutropenia, thrombocytopenia, diarrhea, fatigue, infections, and cerebrovascular accident.
Dosage reduction of ONIVYDE due to an adverse reaction occurred in 52% of patients. Adverse reactions that required dosage reduction in ≥1% of patients included anemia, decreased appetite, diarrhea, fatigue, febrile neutropenia, hypokalemia, liver function test abnormalities, nausea, mucosal inflammation, neutropenia, peripheral neuropathy, vomiting, thrombocytopenia, and weight decreased.
Dosage interruptions of ONIVYDE due to an adverse reaction occurred in 1.9% of patients. Adverse reactions which required dosage interruption in ≥0.5% of patients included hypersensitivity and infusion-related reaction.
The most common laboratory abnormalities (≥10% Grade 3 or 4) were decreased neutrophils (26%), decreased potassium (22%), decreased lymphocytes (11%), and decreased hemoglobin (10%).

ADVERSE REACTIONS FOR ONIVYDE/FU/LV

The most common adverse reactions (≥20%) were diarrhea (59%), fatigue/asthenia (56%), vomiting (52%), nausea (51%), decreased appetite (44%), stomatitis (32%), and pyrexia (23%).
Adverse reactions led to permanent discontinuation of ONIVYDE in 11% of patients receiving ONIVYDE/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/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/FU/LV; the most frequent adverse reactions requiring interruption or delays were neutropenia, diarrhea, fatigue, vomiting, and thrombocytopenia.
The most common severe laboratory abnormalities (≥10% Grade 3 or 4) were lymphopenia and neutropenia.

Postmarketing Experience

The following adverse reactions have been identified during post approval use of ONIVYDE:

Hypersensitivity (including anaphylactic reaction and angioedema).

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: Based on animal data with irinotecan HCl and the mechanism of action of ONIVYDE, ONIVYDE can cause fetal harm when administered to a pregnant woman. There are no available data in pregnant women. Advise pregnant women of the potential risk to a fetus.
Lactation: Advise nursing women not to breastfeed during and for 1 month after the last dose of ONIVYDE.

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, for ONIVYDE.

References: 1. ONIVYDE® [package insert]. Cambridge, MA. Ipsen Biopharmaceuticals, Inc.; 2024. 2. Wainberg ZA, Melisi D, Macarulla T, et al. NALIRIFOX versus nab-paclitaxel and gemcitabine in treatment-naive patients with metastatic pancreatic ductal adenocarcinoma (NAPOLI 3): a randomised, open-label, phase 3 trial. Lancet. 2023;402(10409):1272-1281. 3. Zhang H. Onivyde for the therapy of multiple solid tumors. Onco Targets Ther. 2016;9:3001-3007. 4. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Pancreatic Adenocarcinoma V2.2024. © National Comprehensive Cancer Network, Inc. 2024. All rights reserved. Accessed June 27, 2024. To view the most recent and complete version of the guideline, go online to NCCN.org. 5. 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. 6. 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. 7. CAMPTOSAR® [package insert]. New York, NY. Pfizer, Inc.; 2022. 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. Hsueh C-T, Selim JH, Tsai JY, Hsueh C-T. Nanovectors for anti-cancer drug delivery in the treatment of advanced pancreatic adenocarcinoma. World J Gastroenterol. 2016;22(31):7080-7090. 10. Kelly C, Jefferies C, Cryan S-A. Targeted liposomal drug delivery to monocytes and macrophages. J Drug Deliv. 2011;2011:727241. 11. National Cancer Institute. Drugs approved for pancreatic cancer. https://www.cancer.gov/about-cancer/treatment/drugs/pancreatic. Accessed June 27, 2024. 12. Data on file. Cambridge, MA. Ipsen Biopharmaceuticals, Inc. 2023. 13. Conroy T, Desseigne F, Ychou M, et al; Groupe Tumeurs Digestives of Unicancer; PRODIGE Intergroup. FOLFIRINOX versus gemcitabine for metastatic pancreatic cancer. N Engl J Med. 2011;364(19):1817-1825. 14. Ipsen data on file: ASCO advisory board roundtable. 2023. 15. Wang-Gillam A, Li C-P, Bodoky G, et al; NAPOLI-1 Study Group. 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. 16. Data on file #1. Basking Ridge, NJ. Ipsen Biopharmaceuticals, Inc.; 2015. 17. 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. 18. Ipsen data on file: IQVIA medical claims post-gemcitabine usage analysis, Q4 2017–Q1 2023. 19. Department of Health and Human Services. U.S. Food and Drug Administration. ONIVYDE (irinotecan liposome injection) Approval Letter. NDA 207793. October 22, 2015. https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/207793Orig1s000Approv.pdf. Accessed June 27, 2024.

EFFICACY AND SAFETY STUDIED IN A GLOBAL PHASE 3 CLINICAL TRIAL1,12

NAPOLI-1: a large, phase 3 trial in patients with mPDAC with disease progression after gemcitabine-based therapy12,13

ONIVYDE + 5-FU/LV is the FIRST AND ONLY FDA-approved regimen for mPDAC post-gemcitabine1