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Press Release


Posted on: 18 Oct 16

[Dublin, Ireland] – October 18, , 2016 – Shire plc (LSE: SHP, NASDAQ: SHPG) announced that the European Commission (EC) has granted Marketing Authorization of ONIVYDE® (pegylated liposomal irinotecan hydrochloride trihydrate) also known as nal-IRI or MM-398, for the treatment of metastatic adenocarcinoma of the pancreas, in combination with 5-fluorouracil (5-FU) and leucovorin (LV), in adult patients who have progressed following gemcitabine-based therapy. ONIVYDE is the first and only approved treatment option for this patient population.


With this approval, Shire is authorized to market ONIVYDE in the 28 Member States of the European Union (EU), as well as in Iceland, Liechtenstein and Norway. ONIVYDE was previously approved in the U.S. by the Food and Drug Administration (FDA), in October 2015.


“As the only treatment for metastatic pancreatic cancer following gemcitabine-based therapy that may improve patient survival, ONIVYDE is the first innovation that offers the potential to improve outcomes for this challenging patient population,” said Philip J. Vickers, Ph.D., Global Head of Research and Development at Shire. “The approval of ONIVYDE marks a significant step forward in Shire's focus to develop and commercialize treatments that represent the most promising science in oncology."


Pancreatic cancer is the fourth leading cause of cancer death in the region[[iii] Malvezzi M, Bertuccio P, Levi F, et al. European cancer mortality predictions for the year. Ann Oncol. 2014; 25:1650–1656.

 iii] and there are limited treatment options available.[[iv] Sclafani F, Iyer R, Cunningham D, Starling N. Management of metastatic pancreatic cancer: Current treatment options and potential new therapeutic targets. Critical Reviews in Oncology/Hematology. 2015; (95) 318–336.

 iv] In September 2015, the European Society of Medical Oncology (ESMO) stated that use of MM-398 (ONIVYDE) when available in all countries, may be the best option for patients following gemcitabine-based therapy.[[v] Ducreux M, Cuhna A, Caramella C, et al. Cancer of the pancreas: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2015; 26(5): 56-68.

 v] Gemcitabine-based therapy is commonly used as a first-line treatment for patients with metastatic disease or locally advanced disease that cannot be treated with surgery, or as adjuvant


“The burden of pancreatic cancer for patients, their families and healthcare providers is profound and the treatment options available, especially to those with metastatic disease, have not substantially evolved for decades,” said Alfredo Carrato, M.D., Professor of Medical Oncology at Alcala University and Director of the Medical Oncology Department at Ramon y Cajal University Hospital in Madrid, Spain. “With the approval of ONIVYDE, we have the first and only treatment approved for metastatic adenocarcinoma following gemcitabine-based therapy, and an option that may improve patient survival. This is an important advance for the field of oncology and the lives of those impacted by pancreatic cancer.”


The Marketing Authorization is based on the data from the pivotal, Phase 3 NAPOLI-1 study that demonstrated ONIVYDE combined with 5-FU/LV significantly improved overall survival (OS) (primary endpoint), as well as progression-free survival (PFS) and objective response rate (ORR) relative to the 5-FU/LV control arm (secondary endpoints). In the trial, the most common Grade 3 or higher adverse events with greater than five percent difference in patients receiving ONIVYDE and 5-FU/LV, versus 5-FU/LV alone, were neutropenia, fatigue, diarrhoea, and vomiting.ii


About Pancreatic Cancer

Pancreatic cancer is a significantly underserved disease in Europe and is almost always fatal.[[vi] Carrato A, Falcone A, Ducreux M, et al. A Systematic Review of the Burden of Pancreatic Cancer in Europe: Real-World Impact on Survival, Quality of Life and Costs. J Gastrointest Canc. 2015; 46: 201–211.

 vi] At the time of diagnosis, more than 80 percent of people diagnosed with pancreatic cancer have metastatic disease or locally advanced disease that cannot be removed with surgery.[[vii] Walker EJ and Ko AH. Beyond first-line chemotherapy for advanced pancreatic cancer: An expanding array of therapeutic options? World J Gastroenterol, 2014; 20(9): 2224-36.

 vii] The disease has a median five-year survival rate of about 5 percent,v and an overall median survival of typically less than a year, as supported by real-world European systematic The only curative treatment for pancreatic cancer is surgical resection in the primary stage, which can improve five-year survival to 10 percent.[[viii] Jones OP, Melling JD, and Ghaneh P. Adjuvant therapy in pancreatic cancer. World J Gastroenterol, 2014; 20: 14733-46.



The signs and symptoms of pancreatic cancer are non-specific (common presenting symptoms include jaundice, abdominal pain, weight loss, steatorrhoea, and new-onset diabetes)v and may not appear until the disease has spread locally or metastasized.vii Therefore, most patients are not candidates for surgery upon diagnosis.vii


Even though it accounts for less than three percent of all cancer cases,[[ix] Worldwide data. World Cancer Research Fund Website. Accessed March 8, 2016.

 ix] pancreatic cancer is the seventh leading cause of cancer death worldwide,[[x] Pancreatic cancer statistics. World Cancer Research Fund International. . Accessed March 8, 2016

 x] and the fourth in Europe.iv  Worldwide, pancreatic cancer prognosis is typically poor, with an estimated 337,900 new cases and 330,400 deaths each year.[[xi] Ferlay J, Soerjomataram I, Ervik M, Dikshit R, Eser S, Mathers C, Rebelo M, Parkin DM, Forman D, Bray, F. GLOBOCAN 2012 v1.1, Cancer Incidence and Mortality Worldwide: IARC CancerBase No. 11 [Internet]. Lyon, France: International Agency for Research on Cancer; 2014. Available from:, accessed on 10/17/2016.



About ONIVYDE (nal-IRI)

ONIVYDE is a first-of-its-kind formulation (encapsulation) of irinotecan in a long-circulating liposomal form designed to improve delivery of length of tumor exposure to irinotecan and its active metabolite SN-38. Studies have suggested that encapsulation helps to improve delivery of irinotecan to tumors, such as metastatic pancreatic cancer.[[xii] Ko AH, et al. A multinational phase 2 study of nanoliposomal irinotecan sucrosofate (PEP02, MM-398) for patients with gemcitabine-refractory metastatic pancreatic cancer. British Journal of Cancer. 2013; 109, 920–925



In the pivotal Phase 3 NAPOLI-1 study, ONIVYDE demonstrated significantly improved overall survival in adult patients with metastatic ADENOCARCINOMA of the pancreas who have progressed following gemcitabine-based therapy.ii Gemcitabine, both as monotherapy as well as in combination, is commonly used in the first-line treatment of locally advanced and/or metastatic pancreatic adenocarcinoma, as well as in the adjuvant (treatment after surgery) and neo-adjuvant (treatment before surgery) settings.ii


Shire is responsible for the development and commercialization of ONIVYDE outside of the United States and Taiwan under an exclusive licensing agreement with Merrimack Pharmaceuticals, Inc. (NASDAQ: MACK). Merrimack markets ONIVYDE in the United States after having received US Food and Drug Administration (FDA) approval in October 2015 for the treatment of patients with metastatic adenocarcinoma of the pancreas who have progressed following treatment with gemcitabine-based therapy. ONIVYDE product license was granted in Taiwan in March 2016, where PharmaEngine holds the commercialization rights.


About NAPOLI-1ii

NAPOLI-1 is the first global, randomized open-label Phase 3 trial to show extended overall survival in metastatic pancreatic adenocarcinoma after gemcitabine-based therapy through treatment with ONIVYDE combined with 5-FU and LV. NAPOLI-1 is the largest Phase 3 study in this setting to date showing overall survival benefit. Patients were enrolled at 76 sites in 14 countries across North America, Europe, Asia, South America, and Australia. The study evaluated ONIVYDE (80mg/m2) in combination with 5-FU/LV administered intravenously every two weeks and as a monotherapy (120 mg/m2) administered every three weeks. Each ONIVYDE containing arm was compared to a control arm of 5-FU/LV.


NAPOLI-1 met the following primary and secondary endpoints by demonstrating that ONIVYDE combined with 5-FU/LV significantly improved OS, progression-free survival (PFS) and objective response (OR) compared to 5-FU/LV alone in patients with metastatic pancreatic cancer.i ONIVYDE plus 5-FU/LV demonstrated a significant increase in median overall survival versus 5-FU/LV alone: 6.1 months vs 4.2 months (based on a non-stratified hazard ratio [HR] of 0.67; 95% CI 0.49-0.92, p=0.012).i, ii 


Grade 3 or 4 adverse events that occurred most frequently in the 117 patients assigned ONIVYDE plus 5-FU/LV were neutropenia (32 [27%]), diarrhoea (15 [13%]), vomiting (13 [11%]), and fatigue (16 [14%]).

Editor's Details

Mike Wood

Last updated on: 18/10/2016

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