On October 21, 2018 FUJIFILM Medical Systems U.S.A., Inc., a leading provider of diagnostic imaging and medical informatics solutions, today introduced the FCT Embrace (Press release, Fujifilm, OCT 21, 2018, View Source [SID1234530089]). Powered by Analogic, the FCT Embrace is the world’s first 85cm wide bore computed tomography (CT) imaging unit with 64 or 128 slice configurations. Optimized for both oncology and radiology applications, the FCT Embrace, combined with other market-leading oncology solutions, offers enhanced and efficient CT Simulation with radiotherapy treatment planning capabilities. The unveiling at booth #3063 during the 2018 American Society for Radiation Oncology (ASTRO) Annual Meeting marks Fujifilm’s entry into the CT market, expanding its end-to-end diagnostic imaging product portfolio which is recognized for exceptional imaging at low dose.

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"Fujifilm is a company of ‘firsts’ in diagnostic imaging. In 1936, we took our first steps in the development of X-ray film; and in 1983, we pioneered the first digitized radiography system in the world," said Johann Fernando, Ph.D., Chief Operating Officer of FUJIFILM Medical Systems U.S.A., Inc. "Once again we are innovating with the launch of the FCT Embrace, a solution that provides the most slices ever seen on an 85cm bore system. Designed to improve radiation oncology care, this advanced solution boosts patient comfort and security by offering the widest tabletop currently available at 49cm, and accommodating bariatric patients of up to 660lbs."

The new, state-of-the-art FCT Embrace provides exceptional imaging capabilities on an easy-to-use, standardized platform for both radiology and oncology. Designed to improve accuracy throughout the entire oncology care cycle, the 85cm bore optimally matches the rotational arc of the linear accelerator—offering easy and precise positioning options for simulation and treatment planning. This unique solution allows oncology patients to be imaged in their optimal treatment position at the full clinical image quality afforded by 64 slice or greater systems for the first time; maintaining the accuracy requirements radiation oncology demands without compromising diagnostic image quality.

With over 80 years of medical imaging experience, Fujifilm’s expertise in brilliant image quality, low dose, and patient comfort is now available to the CT market for oncology, interventional CT and radiology.

For more information on Fujifilm’s solutions, please visit: www.fujimed.com.

On October 21, 2018 Genmab A/S (Nasdaq Copenhagen: GEN) reported the study met its primary endpoint for Part 1 of the Phase III CASSIOPEIA study (MMY3006) of daratumumab in combination with bortezomib, thalidomide and dexamethasone (VTD) versus VTD alone as frontline treatment for patients who are candidates for autologous stem cell transplant (ASCT) (Press release, Genmab, OCT 21, 2018, View Source [SID1234530041]). The first part of the study met the primary endpoint of number of patients that achieved a sCR, which was reported in 28.9% of patients treated with daratumumab in combination with VTD, compared to 20.3% of patients who received VTD alone with an odds ratio of 1.60 (95% CI: 1.21 – 2.12, p ≤ 0.001). In the second part of the study, all responders have been re-randomized to receive either maintenance treatment with daratumumab monotherapy or observation (no treatment).

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Overall, the safety profile of daratumumab in combination with VTD is consistent with the known safety profile of the VTD regimen used in patients receiving ASCT and the known safety profile for daratumumab.

Further analysis of the safety and efficacy data is ongoing and Janssen Biotech, Inc., which licensed daratumumab from Genmab in 2012, will discuss the potential for regulatory submissions for this indication with health authorities and IFM/HOVON plans to submit additional data for presentation at an upcoming medical conference and for publication in a peer-reviewed journal.

"Having previously seen positive data in the ALCYONE trial, for the frontline treatment of patients ineligible for autologous stem cell transplant, we are very pleased to see the results from the CASSIOPEIA study, which presents exciting insights into the potential of daratumumab for newly diagnosed multiple myeloma patients who received an autologous stem cell transplantation (ASCT). We also look forward to the data from the second part of the study, which will provide further data on the impact of daratumumab monotherapy as maintenance treatment," said Jan van de Winkel, Ph.D., Chief Executive Officer of Genmab.

Today’s news does not impact Genmab’s 2018 financial guidance.

About the CASSIOPEIA (MMY3006) study
This Phase III study is a randomized, open-label, multicenter study, run by the French Intergroupe Francophone du Myelome (IFM) in collaboration with the Dutch-Belgian Cooperative Trial Group for Hematology Oncology (HOVON) and Janssen Biotech, Inc., including 1,085 newly diagnosed subjects with previously untreated symptomatic multiple myeloma who are eligible for high dose chemotherapy and stem cell transplant. In the first part of the study, patients were randomized to receive induction and consolidation treatment with daratumumab combined with bortezomib, thalidomide (an immunomodulatory agent) and dexamethasone (a corticosteroid) or bortezomib, thalidomide and dexamethasone alone. The primary endpoint is the number of patients that achieve a sCR. In the second part of the study, patients that achieved a response will undergo a second randomization to either receive maintenance treatment of daratumumab 16 mg/kg every 8 weeks for up to 2 years versus no further treatment (observation). The primary endpoint of this part of the study is progression free survival (PFS).

About multiple myeloma
Multiple myeloma is an incurable blood cancer that starts in the bone marrow and is characterized by an excess proliferation of plasma cells.1 Multiple myeloma is the third most common blood cancer in the U.S., after leukemia and lymphoma.2 Approximately 30,770 new patients are expected to be diagnosed with multiple myeloma and approximately 12,770 people are expected to die from the disease in the U.S. in 2018.3 Globally, it was estimated that 124,225 people would be diagnosed and 87,084 would die from the disease in 2015.4 While some patients with multiple myeloma have no symptoms at all, most patients are diagnosed due to symptoms which can include bone problems, low blood counts, calcium elevation, kidney problems or infections.5

About DARZALEX(daratumumab)
DARZALEX (daratumumab) injection for intravenous infusion is indicated in the United States in combination with bortezomib, melphalan and prednisone for the treatment of patients with newly diagnosed multiple myeloma who are ineligible for autologous stem cell transplant; in combination with lenalidomide and dexamethasone, or bortezomib and dexamethasone, for the treatment of patients with multiple myeloma who have received at least one prior therapy; in combination with pomalidomide and dexamethasone for the treatment of patients with multiple myeloma who have received at least two prior therapies, including lenalidomide and a proteasome inhibitor (PI); and as a monotherapy for the treatment of patients with multiple myeloma who have received at least three prior lines of therapy, including a PI and an immunomodulatory agent, or who are double-refractory to a PI and an immunomodulatory agent.6 DARZALEX is the first monoclonal antibody (mAb) to receive U.S. Food and Drug Administration (U.S. FDA) approval to treat multiple myeloma. DARZALEX is indicated in Europe in combination with bortezomib, melphalan and prednisone for the treatment of adult patients with newly diagnosed multiple myeloma who are ineligible for autologous stem cell transplant; for use in combination with lenalidomide and dexamethasone, or bortezomib and dexamethasone, for the treatment of adult patients with multiple myeloma who have received at least one prior therapy; and as monotherapy for the treatment of adult patients with relapsed and refractory multiple myeloma, whose prior therapy included a PI and an immunomodulatory agent and who have demonstrated disease progression on the last therapy. In Japan, DARZALEX is approved in combination with lenalidomide and dexamethasone, or bortezomib and dexamethasone, for treatment of adults with relapsed or refractory multiple myeloma. DARZALEX is the first human CD38 monoclonal antibody to reach the market. For more information, visit www.DARZALEX.com.

Daratumumab is a human IgG1k monoclonal antibody (mAb) that binds with high affinity to the CD38 molecule, which is highly expressed on the surface of multiple myeloma cells. Daratumumab triggers a person’s own immune system to attack the cancer cells, resulting in rapid tumor cell death through multiple immune-mediated mechanisms of action and through immunomodulatory effects, in addition to direct tumor cell death, via apoptosis (programmed cell death).6,7,8,9,10

Daratumumab is being developed by Janssen Biotech, Inc. under an exclusive worldwide license to develop, manufacture and commercialize daratumumab from Genmab. A comprehensive clinical development program for daratumumab is ongoing, including multiple Phase III studies in smoldering, relapsed and frontline multiple myeloma settings and in amyloidosis. Additional studies are ongoing or planned to assess the potential of daratumumab in other malignant and pre-malignant diseases, such as NKT-cell lymphoma, myelodysplastic syndromes, B and T-ALL. Daratumumab has received two Breakthrough Therapy Designations from the U.S. FDA, for multiple myeloma, as both a monotherapy and in combination with other therapies.

On October 21, 2018 Leap Therapeutics, Inc. (NASDAQ: LPTX) reported its clinical data from its ongoing Phase I/II study of DKN-01 in combination with Keytruda (pembrolizumab) in patients with advanced esophagogastric cancer at the European Society for Molecular Oncology (ESMO) (Free ESMO Whitepaper) 2018 Annual Congress (Press release, Leap Therapeutics, OCT 21, 2018, View Source [SID1234530017]).

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Leap will host a live conference call and webcast on Monday, October 22 at 8:00 AM US Eastern Time / 2:00 PM Central European Time, with Samuel Klempner, MD, Director, Precision Medicine Program, The Angeles Clinic and Research Institute, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center. Dr. Klempner will describe his experience with patients in the study.

Clinical Data Presented at ESMO (Free ESMO Whitepaper)

Midway through the study, the combination of DKN-01 and pembrolizumab has demonstrated promising clinical activity with a 23.5% overall response rate and 58.8% disease control rate in evaluable gastric or gastroesophageal junction cancer patients who have been heavily pretreated and have not had prior anti-PD-1/PD-L1 therapy (PD-1/PD-L1 naïve). The combination has generated durable responses in subgroups less likely to respond to pembrolizumab monotherapy, for example, patients whose tumors are microsatellite stable (MSS) and/or PD-L1 negative. The combination of DKN-01 and pembrolizumab may have additive clinical benefit through the targeting of both innate and adaptive immunity. Data to date suggest that elevated tumor expression of DKK1 may correlate with better patient outcomes. Biomarker analyses are underway to guide future clinical development in gastroesophageal malignancies.

Esophagogastric Cancer Clinical Trial (P102)

The esophagogastric cancer clinical trial (P102) is a multipart study of DKN-01 as a monotherapy and in combination with paclitaxel or pembrolizumab. The arm evaluating DKN- 01 plus pembrolizumab includes both dose escalation and dose confirmation cohorts and is designed to assess the safety, pharmacokinetics and efficacy of the combination. Data from the monotherapy and paclitaxel arms of the study have been presented previously and will be updated later in the year.

As of the September 26, 2018 cut-off date for the presentation, forty-five patients have been enrolled in the DKN-01 plus pembrolizumab study, thirty-eight PD-1/PD-L1 naïve and seven refractory to PD-1/PD-L1 therapy. Two of the patients were enrolled in the 150mg DKN-01 dose, and forty-three patients at the 300mg DKN-01 dose. Leap expects that the PD-1/PD-L1 naïve group will complete enrollment before the end of 2018.

DKN-01 plus Keytruda
Clinical Results as of September 26, 2018

300mg DKN-01
Anti-PD1/PD-L1 Naïve

Patients

Response Rate

Disease
Control
Rate

Partial Response

Stable Disease

Progressive Disease

All responding patients in the study had MSS tumors. The overall response rate for Keytruda monotherapy in gastric or gastroesophageal junction patients with non-microsatellite instability high tumors in the KN-059 (n = 167) and KN-061 (n = 281) studies was 9.0% and 9.3%, respectively.

When this study is complete, Leap expects to choose an indication for a larger, controlled clinical study.

DKN-01 Clinical Perspectives Conference Call and Webcast:

On Monday, October 22, 2018 at 8:00AM ET/2:00PM CET, Leap will be hosting a conference call and webcast for the investment community. To access the conference call, please dial (866) 589-0108 (US/Canada Toll-Free) or (409) 231-2048 (international) and refer to conference ID 1249999. The presentation will also be webcast live and will be available under "Events & Presentations" in the Investor section of Leap’s website, View Source A replay of the webcast will be available on Leap’s website approximately two hours after the event and will be available for a limited time.

On October 21, 2018 Daiichi Sankyo Company, Limited (hereafter, Daiichi Sankyo) reported that updated phase 1 safety and efficacy data for [fam-] trastuzumab deruxtecan, an investigational HER2 targeting antibody drug conjugate (ADC), were presented for a subgroup of patients with heavily pretreated HER2 expressing colorectal cancer at the 2018 European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Congress in Munich, Germany (Press release, Daiichi Sankyo, OCT 21, 2018, https://www.prnewswire.com/news-releases/daiichi-sankyo-presents-updated-results-of-fam–trastuzumab-deruxtecan-ds-8201-in-patients-with-her2-expressing-advanced-colorectal-cancer-at-2018-european-society-for-medical-oncology-esmo-congress-300734400.html [SID1234530016]).

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An updated subgroup analysis in 19 evaluable patients with heavily pretreated HER2 expressing (defined as IHC ≥1+ or amplified) colorectal cancer receiving a recommended expansion dose of 6.4 mg/kg showed that [fam-] trastuzumab deruxtecan demonstrated a confirmed overall response rate of 15.8 percent (3 of 19 patients) and a disease control rate of 84.2 percent (16 of 19 patients). Median duration of response has not been reached and median progression-free survival was 3.9 months (95 percent CI: 2.1, 8.3) for this subgroup of patients. These patients had tumors with varying degrees of HER2 expression based on central IHC assessment of archival tissue, including six patients with HER2 IHC of zero (0). Tumor shrinkage primarily was observed in tumors with higher levels of HER2 IHC.

"We are encouraged by these preliminary results with [fam-] trastuzumab deruxtecan, particularly given the unmet medical need for patients with HER2 expressing colorectal cancer that has progressed on one or more prior therapies," said Takayuki Yoshino, MD, PhD, Director of Gastroenterology and Gastrointestinal Oncology at National Cancer Center Hospital East, Kashiwa, Japan, a study investigator. "These initial findings support further evaluation of [fam-] trastuzumab deruxtecan in this specific type of colorectal cancer."

"There are no therapies specifically approved for patients with HER2 expressing colorectal cancer, and continued study of [fam-] trastuzumab deruxtecan will provide a better understanding of the potential role of a HER2 targeting antibody drug conjugate in these patients," said Gilles Gallant, BPharm, PhD, Vice President, DS-8201 Global Team Leader, Oncology Research and Development, Daiichi Sankyo. "Patient enrollment is underway into our global phase 2 study evaluating safety and efficacy of [fam-] trastuzumab deruxtecan in patients with HER2 expressing advanced colorectal cancer."

Updated overall safety data as of August 10, 2018 across all subgroups of the ongoing phase 1 study with [fam-] trastuzumab deruxtecan in various HER2 expressing cancers were also reported at ESMO (Free ESMO Whitepaper). Among 259 patients who received at least one dose of [fam-] trastuzumab deruxtecan 5.4 or 6.4 mg/kg in Part 1 or Part 2 of the study (regardless of tumor type), the most common adverse events (≥30 percent, any Grade) included nausea (74.1 percent), decreased appetite (56.8 percent;) vomiting (43.6 percent), anemia (37.8 percent), alopecia (37.5 percent), fatigue (34.0 percent), diarrhea (33.6 percent) and constipation (32.8 percent). A total of 54.1 percent of patients experienced a ≥ Grade 3 adverse event and 22.8 percent had a serious adverse event, including 4.6 percent of patients who experienced an adverse event that led to death. As previously presented, five cases of Grade 5 interstitial lung disease (ILD)/pneumonitis were reported by the investigators for the overall population of the phase 1 study, none of which was observed in patients with colorectal cancer. Any reported cases of ILD/pneumonitis in the [fam-] trastuzumab deruxtecan clinical development program are evaluated by an independent adjudication committee.

Unmet Need in Colorectal Cancer
Colorectal cancer is the third most common cancer worldwide. In 2012, there were approximately 1.36 million new cases diagnosed and 690,000 deaths worldwide.1 Approximately 25 percent of patients have metastatic disease at diagnosis, meaning the disease has spread to distant organs, and about 50 percent of patients with colorectal cancer will eventually develop metastases.2 Prognosis for these patients remains poor.3

An increase in the number of approved targeted therapies for advanced colorectal cancer over the past decade has helped improve outcomes for some patients, however efficacy and tolerability of second and third-line treatments remain limited.4,5,6,7,8 Approximately 3 percent of colorectal cancers overexpress the HER2 protein, which is a well-established therapeutic target in breast and gastric cancer.4 In addition, research indicates that HER2 amplification may be associated with resistance to anti-epidermal growth factor receptor (EGFR)-targeted therapy and shorter survival.9,10 Currently, no approved HER2 targeting therapies exist for patients with colorectal cancer.

About the [Fam-] Trastuzumab Deruxtecan Phase 1 Study
An open-label, two-part phase 1 study is currently evaluating [fam-] trastuzumab deruxtecan in patients with advanced/unresectable or metastatic solid tumors that are refractory or intolerant to standard treatment, or for whom no standard treatment is available. The primary objective of the dose escalation phase of this study was to assess the safety and tolerability of [fam-] trastuzumab deruxtecan and determine the maximum tolerated dose. Data from this part of the study were published in the Lancet Oncology.11

In the dose expansion part of the phase 1 study, [fam-] trastuzumab deruxtecan is given in one of two doses (5.4 mg/kg and 6.4 mg/kg) to patients with HER2 positive advanced or metastatic breast cancer and gastric cancer, HER2 low expressing breast cancer and other HER2 expressing solid tumors including colorectal cancer. Overall, 292 patients have been enrolled into this phase 1 study of [fam-] trastuzumab deruxtecan. For more information about the study, visit ClinicalTrials.gov.

About [Fam-] Trastuzumab Deruxtecan
[Fam-] trastuzumab deruxtecan (DS-8201; [fam-] trastuzumab deruxtecan in U.S. only; trastuzumab deruxtecan in other regions of world) is the lead product in the investigational ADC Franchise of the Daiichi Sankyo Cancer Enterprise. ADCs are targeted cancer medicines that deliver cytotoxic chemotherapy ("payload") to cancer cells via a linker attached to a monoclonal antibody that binds to a specific target expressed on cancer cells. Designed using Daiichi Sankyo’s proprietary ADC technology, [fam-] trastuzumab deruxtecan is comprised of a humanized HER2 antibody attached to a novel topoisomerase I inhibitor payload by a tetrapeptide-based linker. It is designed to target and deliver chemotherapy inside cancer cells and reduce systemic exposure to the cytotoxic payload (or chemotherapy) compared to the way chemotherapy is commonly delivered.

A broad and comprehensive development program with [fam-] trastuzumab deruxtecan is underway in North America, Europe and Asia. [Fam-] trastuzumab deruxtecan is in phase 3 development versus ado-trastuzumab emtansine (T-DM1) (DESTINY-Breast03) and versus investigator’s choice post T-DM1 (DESTINY-Breast02) for HER2 positive metastatic breast cancer; pivotal phase 2 clinical development for HER2 positive metastatic breast cancer resistant or refractory to T-DM1 (DESTINY-Breast01); pivotal phase 2 development for HER2 positive advanced gastric cancer resistant or refractory to trastuzumab (DESTINY-Gastric01); phase 2 development for HER2 expressing advanced colorectal cancer; phase 2 development for metastatic non-squamous HER2 overexpressing or HER2 mutated NSCLC; and, phase 1 development in combination with nivolumab for HER2 expressing metastatic breast and bladder cancer.

[Fam-] trastuzumab deruxtecan has been granted Breakthrough Therapy designation for the treatment of patients with HER2 positive, locally advanced or metastatic breast cancer who have been treated with trastuzumab and pertuzumab and have disease progression after T-DM1, and Fast Track designation for the treatment of HER2 positive unresectable and/or metastatic breast cancer in patients who have progressed after prior treatment with HER2 targeted therapies including T-DM1 by the U.S. Food and Drug Administration (FDA). [Fam-] trastuzumab deruxtecan has received SAKIGAKE Designation for the treatment of HER2 positive advanced gastric or gastroesophageal junction cancer by the Japan Ministry of Health, Labour and Welfare (MHLW).

[Fam-] trastuzumab deruxtecan is an investigational agent that has not been approved for any indication in any country. Safety and efficacy have not been established.

On October 21, 2018 Ipsen Biopharmaceuticals, an affiliate of Ipsen (Euronext: IPN; ADR: IPSEY), reported results from a retrospective, observational analysis examining the real-world dosing patterns of patients with metastatic pancreatic cancer (mPC) treated with ONIVYDE (irinotecan liposome injection), at this year’s European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) annual congress taking place in Munich, Germany, Oct. 19-23, 2018 (Press release, Ipsen, OCT 21, 2018, View Source [SID1234530015]).

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Using the Flatiron Health electronic health record (EHR)-derived database, a longitudinal and nationally representative database comprising patient-level structured and unstructured data that is curated via technology-enabled abstraction, researchers identified 257 metastatic pancreatic cancer patients (median age: 67y; IQR: 61–74) who received ONIVYDE + fluorouracil (5-FU) and leucovorin (LV) therapy between November 2015 to August 2017 and analyzed their treatment data to assess dose intensity (DI) over the first 6 weeks of treatment, dose modifications during treatment, and overall duration of exposure (DOE) to ONIVYDE.

The real-world analysis (Poster 735P) describes how ONIVYDE was incorporated in the treatment sequencing that contained prior gemcitabine in the treatment of metastatic pancreatic cancer. In this analysis, the mean dose intensity was 177.8 mg/m2 (SD: 74.9 mg/m2). The median dose at initiation was 69.4 mg/m2 (IQR: 56.7–70.2); the recommended dose for ONIVYDE is 70 mg/m2. In addition, median duration of exposure was 8.9 weeks (IQR: 3.9/19 weeks) in first and second line and 6.3 weeks (IQR: 3.4/12.1 weeks) in third or plus lines.

These results are generally consistent with the NAPOLI-1 trial, however, dose modifications in the real-world analysis were lower (27.2% vs 45% in NAPOLI-1). In the NAPOLI-1 phase 3 trial, dose intensity over 6 weeks and duration of exposure for combination therapy with ONIVYDE was 167.5 mg/m2 (SD 44.8) and 8.7 weeks (IQR: 5.4 – 22.0), respectively. Despite these real-world patients being older, having worse performance status and more prior lines of treatment than patients in NAPOLI-1, more than half (59.1%) of patients started ONIVYDE + 5-FU/LV treatment with the recommended ONIVYDE dose (70 mg/m2).

NAPOLI-1 is the largest global, phase 3, randomized, open-label, multicenter trial in patients (N=417) with metastatic pancreatic cancer whose disease had progressed following gemcitabine-based therapy. Patients in the NAPOLI-1 trial being treated with ONIVYDE in combination with fluorouracil (5-FU) and leucovorin (LV) had improved overall survival (OS; primary endpoint) vs 5-FU/LV (6.1 mos vs 4.2 mos; HR = 0.67, 95% CI 0.49–0.92; P = 0.012). ONIVYDE monotherapy had no effect on OS.

ONIVYDE can cause severe, life-threatening neutropenia and diarrhea (see complete Boxed Warning in full prescribing information). ONIVYDE can also cause severe and fatal Interstitial Lung Disease (ILD) and hypersensitivity reactions. These serious adverse events may require withholding or discontinuing treatment with ONIVYDE, a dose reduction and/or supportive treatment. The most common adverse reactions in NAPOLI-1 (≥20%) were diarrhea (59%), fatigue/asthenia (56%), vomiting (52%), nausea (51%), decreased appetite (44%), stomatitis (32%), and pyrexia (23%).

"Patients are at the heart of what we do, with unmet need guiding our development strategy and driving how we innovate for patient care," said Dr. Sotirios Stergiopoulos, Senior Vice President, Head of Global Medical Affairs and Chief Medical Officer. "This real-world data analysis provides further evidence in support of the dose intensity and duration of exposure of ONIVYDE and 5-FU/LV observed in the NAPOLI-1 phase 3 trial. This retrospective analysis allows us to further understand how patients with pancreatic cancer are receiving and managing their treatment in real-world settings."

Dr. Afsaneh Barzi, Study Investigator, Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, Calif., notes, "As a physician who treats patients with metastatic pancreatic cancer, I find it reassuring and welcome the unique evidence the Flatiron dosing analysis provides in demonstrating the real-world usage of ONIVYDE + 5-FU/LV in a large sample of metastatic pancreatic cancer patients being treated in a clinical oncology setting when compared to a clinical trial setting. Data from our real-world practice for clinical analysis serve to further our knowledge about how to continue to effectively treat our patients."

About Pancreatic Cancer

Pancreatic cancer is a rare and deadly disease with about 55,440 people (29,200 men and 26,240 women) being diagnosed with pancreatic cancer in the United States alone.1 More than half are diagnosed with metastatic disease, which has an overall 5-year survival rate of less than three percent (3%)1, and often rapidly progresses during or shortly after receiving chemotherapy.2 Pancreatic cancer accounts for about 3% of all cancers, and is the third leading cause of cancer-related death in the United States, surpassing breast cancer.1 It is expected to become the second leading cause of cancer-related death in the U.S. by the year 2030, surpassing colorectal cancer.1,3

About ONIVYDE

ONIVYDE is an encapsulated formulation of irinotecan. This long-circulating liposomal form is designed to increase length of tumor exposure to both irinotecan and its active metabolite, SN38. ONIVYDE is approved by the U.S. FDA, EMA and many other countries. In the U.S., ONIVYDE is approved for use 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. ONIVYDE is not indicated as a single agent for the treatment of patients with metastatic adenocarcinoma of the pancreas. Ipsen has gained exclusive commercialization rights for the current and potential future indications for ONIVYDE in the U.S., as well as the current licensing agreements with Servier for commercialization rights ex-U.S. and PharmaEngine for Taiwan.

IMPORTANT SAFETY INFORMATION:

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 fluorouracil (5-FU) and leucovorin (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.

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