ONIVYDE® (irinotecan liposome for injection) has Received Approval in Canada for the Treatment of Metastatic Adenocarcinoma of the Pancreas in the Post-Gemcitabine Setting(1)

ONIVYDE, in combination with 5-fluorouracil (5-FU) and leucovorin (LV), is the first and only treatment shown to increase median overall survival by up to two months for adult pancreatic cancer patients who have disease progression following gemcitabine-based therapy.²

TORONTO, Aug. 11, 2017 /CNW/ - Shire Pharma Canada ULC (Shire Canada) today announced that ONIVYDE (irinotecan liposome for injection) has been approved for the treatment of metastatic adenocarcinoma of the pancreas, in combination with 5-fluorouracil (5-FU) and leucovorin (LV), in adult patients who have disease progression following gemcitabine-based therapy.³ ONIVYDE is the first and only approved treatment option for this patient population who have no universally accepted standard of treatment until now.⁴ Based on the NAPOLI-1 trial, ONIVYDE has been shown to extend patients' overall survival by two additional months.⁵

"At Shire, we have a clear goal to develop and deliver innovative therapies for underserved cancer patients in need of breakthrough therapies," said Eric Tse, General Manager of Shire Canada. "We are proud to launch ONIVYDE in Canada and continue our mission of making a real difference in the lives of people living with cancer."

Pancreatic cancer is the fourth leading cause of cancer-related death in Canada. Yet little progress has been made in preventing, detecting and treating the disease relative to other leading cancer killers.⁶ Survival rates for pancreatic cancer remain the lowest among other types of cancer. If recent trends continue, the disease is expected to surpass breast cancer as the third leading cause of cancer deaths in the country.⁷ 

With the pancreas so deep in the abdomen, about 60 per cent of pancreatic cancers are detected at a late stage, which significantly contributes to its poor prognosis.⁸ It is estimated that 5,500 Canadians will be diagnosed with pancreatic cancer in 2017, but only 50 per cent of those are expected to survive beyond about four months after diagnosis.⁹ While first-line treatments are available to patients, disease progression after initial therapy is common, leaving patients with no options for further treatment.¹⁰ About 4,800 Canadians are predicted to succumb to pancreatic cancer this year.¹¹

"There have been very few treatment advancements for metastatic pancreatic cancer over the years.  Until now, when patients failed on their first line drug, they would be left without any good options," says Dr. Jeff Rothenstein, medical oncologist at the R.S. McLaughlin Durham Regional Cancer Center in Oshawa. "The approval of ONIVYDE means pancreatic cancer patients have another treatment option that could help them continue their fight against the disease."

ONIVYDE was evaluated in NAPOLI-1, the first global, phase III trial to demonstrate a positive outcome in patients with disease progression following gemcitabine-based therapy.¹² Patients who received ONIVYDE in combination with 5-FU/LV saw significant improvements in median overall survival (45 per cent increase), progression-free survival (100 per cent increase) and objective response rate (16.2 per cent) relative to those who received 5-FU/LV alone (0.8 per cent).¹³

"Treating pancreatic cancer is challenging, especially given the disease's vague symptoms which are often mistaken for benign conditions. This frequent misdiagnosis means many patients are diagnosed with pancreatic cancer at a late stage," says Stefanie Condon-Oldreive, Founder and Director of Craig's Cause Pancreatic Cancer Society. "This new treatment is exciting news because it means patients have a new option to turn to, one that could improve their quality of life and provide them with meaningful time with those they love. For pancreatic cancer patients, that time is of the utmost importance."

"We lose thousands of Canadians to pancreatic cancer every year and yet we don't see quite as much advancement in the treatment of this disease compared to other types of cancer," says Michelle Capobianco, Executive Director of Pancreatic Cancer Canada. "This new treatment option is a step in the right direction and is the kind of progress we want to see for years to come."

About ONIVYDE

ONIVYDE is indicated for the treatment of metastatic adenocarcinoma of the pancreas, in combination with 5-fluorouracil (5-FU) and leucovorin (LV), in adult patients who have disease progression following gemcitabine-based therapy.¹⁴

ONIVYDE's active ingredient irinotecan is encapsulated in a long-circulating liposomal form.¹⁵ Through this unique delivery system, ONIVYDE prolongs drug circulation and may lead to increased accumulation of the drug and its active metabolite (SN-38) in the tumor.¹⁶ Studies have suggested that encapsulation helps to improve delivery of irinotecan to tumors, such as metastatic pancreatic cancer.¹⁷

Do not substitute ONIVYDE for or with other drug products containing irinotecan. ONIVYDE is not indicated as a single agent for the treatment of patients with metastatic adenocarcinoma of the pancreas and should only be administered under the supervision of a physician who is experienced in the use of cancer chemotherapeutic agents.¹⁸

ONIVYDE should not be taken by patients who have experienced severe hypersensitivity reactions to ONIVYDE, other non-liposomal irinotecan or any other ingredient in the formulation or component of the container. It should also not be taken while breastfeeding.¹⁹

Patients may experience diarrhea while on ONIVYDE and should be monitored closely, and given fluids and electrolytes as needed. Early onset diarrhea can occur with cholinergic symptoms, but happen infrequently and can be treated with atropine. Late onset diarrhea can be life threatening and must be treated promptly with loperamide or equivalent medications. Antibiotic therapy should be administered if patients develop ileus (a lack of movement in the intestines), fever or severe neutropenia (abnormally low levels of white blood cells that helps fight infection²⁰).²¹

ONIVYDE is a registered trademark used under license from Ipsen Biopharm Ltd.

About NAPOLI-1

NAPOLI-1 is a randomized, open-label, multicentre, global, phase III trial in 417 patients with metastatic adenocarcinoma of the pancreas who had progressed following gemcitabine-based therapy.²² Patients were enrolled in 76 sites in 14 across North America, South America, Europe, Asia and Australia.²³

The study evaluated three regimens: 5-fluorouracil (5-FU) and leucovorin (LV), ONIVYDE in combination with 5-FU/LV and ONIVYDE as a monotherapy.²⁴ Patients randomized to ONIVYDE+5-FU/LV arm received ONIVYDE 70 mg/m² as an intravenous infusion over 90 minutes, followed by LV 400 mg/m² intravenously over 30 minutes, followed by 5-FU 2400 mg/m² intravenously over 46 hours, every 2 weeks. The ONIVYDE dose of 70 mg/m2 is based on irinotecan anhydrous free base (equivalent to 80 mg/m² of irinotecan as the hydrochloride trihydrate).²⁵

NAPOLI-1 demonstrated that ONIVYDE combined with 5-FU/LV improved overall survival by 45 per cent and progression-free survival by 100 per cent as well as displayed an objective response rate of 16.2 per cent compared to 0.8 per cent with 5-FU/LV alone.²⁶ 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).²⁷

The following adverse events occurred at a higher incidence in the ONIVYDE+5-FU/LV arm or ONIVYDE arm than in the 5-FU/LV arm (arm difference of ≥5%, Grade 1-4): diarrhea (59 per cent), vomiting (52 per cent), nausea (51 per cent), decreased appetite (44 per cent), fatigue (40 per cent), neutropenia or a decrease in neutrophil white blood cells (39 per cent), anemia (38 per cent) and hypokalemia or decreased potassium level (12 per cent).²⁸ Grade 3 or 4 adverse events that occurred most frequently in patients assigned ONIVYDE plus 5-FU/LV were neutropenia (27 per cent), diarrhea (13 per cent), vomiting (11 per cent), and fatigue (14 per cent).²⁹

About Pancreatic Cancer

Most pancreatic cancers start in exocrine cells which produce enzymes that help the body digest food and absorb nutrients.³⁰ As the pancreas is located so deep in the abdomen, pancreatic cancer often develop for weeks or months without presenting symptoms.³¹ As tumors grow, they begin to put pressure on nearby organs causing pain, nausea, weight loss, jaundice and itching.³²

Most cases of pancreatic cancer are discovered at a late stage when curative surgery is no longer an option. It is also relatively unresponsive to chemotherapy and radiation. As a result, prognosis for the disease is often poor.³³

About Shire

Shire is the leading global biotechnology company focused on serving people with rare diseases and other highly specialized conditions. We strive to develop best-in-class products, many of which are available in more than 100 countries, across core therapeutic areas including Hematology, Immunology, Neuroscience, Ophthalmics, Lysosomal Storage Disorders, Gastrointestinal / Internal Medicine / Endocrine and Hereditary Angioedema; and a growing franchise in Oncology.

Our employees come to work every day with a shared mission: to develop and deliver breakthrough therapies for the hundreds of millions of people in the world affected by rare diseases and other high-need conditions, and who lack effective therapies to live their lives to the fullest.

About Shire Pharma Canada ULC

Shire Pharma Canada ULC is a subsidiary of Shire. Our Canadian office is located in Toronto, Ontario. For more information, please visit: www.shirecanada.com.

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^1	Onivyde Product Monograph. August 8, 2017.
^2	Onivyde Product Monograph. August 8, 2017.
^3	Onivyde Product Monograph. August 8, 2017.
^4	Wang-Gillam A, 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. The Lancet. 2016; 387(10018):545-557.
^5	Onivyde Product Monograph. August 8, 2017.
^6	Canadian Cancer Society. Canadian Cancer Statistics 2017 – Special topic: Pancreatic cancer.
^7	Canadian Cancer Society. Canadian Cancer Statistics 2017 – Special topic: Pancreatic cancer.
^8	Canadian Cancer Society. Canadian Cancer Statistics 2017 – Special topic: Pancreatic cancer.
^9	Canadian Cancer Society. Canadian Cancer Statistics 2017 – Special topic: Pancreatic cancer.
^10	Wang-Gillam A, 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. The Lancet. 2016; 387(10018):545-557.
^11	Canadian Cancer Society. Canadian Cancer Statistics 2017 – Special topic: Pancreatic cancer.
^12	Onivyde Product Monograph. August 8, 2017.
^13	Onivyde Product Monograph. August 8, 2017.
^14	Onivyde Product Monograph. August 8, 2017.
^15	Onivyde Product Monograph. August 8, 2017.
^16	Onivyde Product Monograph. August 8, 2017.
^17	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
^18	Onivyde Product Monograph. August 8, 2017.
^19	Onivyde Product Monograph. August 8, 2017.
^20	Mayo Foundation for Medical Education and Research. Neutropenia (low neutrophil count). http://www.mayoclinic.org/symptoms/neutropenia/basics/definition/sym-20050854. Last accessed August 9, 2017.
^21	Onivyde Product Monograph. August 8, 2017.
^22	Wang-Gillam A, 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. The Lancet. 2016; 387(10018):545-557.
^23	Wang-Gillam A, 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. The Lancet. 2016; 387(10018):545-557.
^24	Wang-Gillam A, 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. The Lancet. 2016; 387(10018):545-557.
^25	Wang-Gillam A, 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. The Lancet. 2016; 387(10018):545-557.
^26	Wang-Gillam A, 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. The Lancet. 2016; 387(10018):545-557.
^27	Wang-Gillam A, 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. The Lancet. 2016; 387(10018):545-557.
^28	Wang-Gillam A, 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. The Lancet. 2016; 387(10018):545-557.
^29	Wang-Gillam A, 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. The Lancet. 2016; 387(10018):545-557.
^30	Canadian Cancer Society. Canadian Cancer Statistics 2017 – Special topic: Pancreatic cancer.
^31	Canadian Cancer Society. Canadian Cancer Statistics 2017 – Special topic: Pancreatic cancer.
^32	Canadian Cancer Society. Canadian Cancer Statistics 2017 – Special topic: Pancreatic cancer.
^33	Canadian Cancer Society. Canadian Cancer Statistics 2017 – Special topic: Pancreatic cancer.

SOURCE Shire Pharma Canada ULC

Amanda Jacobs, Communications, Shire Canada, [email protected], [phone]