Ipsen Completes Acquisition Of ONIVYDE (Irinotecan Liposome Injection) And Additional Oncology Assets From Merrimack
- Significantly expands Ipsen’s growing oncology portfolio
- Immediate U.S. commercialization rights for ONIVYDE® for metastatic pancreatic cancer in adult patients1
PARIS--(BUSINESS WIRE)--Regulatory News:
“Together with our experienced commercial and medical teams and the legacy we have gained through the acquisition of ONIVYDE®, we are confident in our ability to meet the growing needs of these patients.”
Ipsen (Euronext: IPN; ADR: IPSEY) announced today that it has completed its acquisition of global oncology assets from Merrimack Pharmaceuticals, in Cambridge, MA., focusing on ONIVYDE® (irinotecan liposome injection) for the treatment of patients with metastatic adenocarcinoma of the pancreas after disease progression following gemcitabine-based therapy, in combination with fluorouracil and leucovorin.1,2 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 Shire for commercialization rights ex-U.S. and PharmaEngine for Taiwan. The acquisition also includes the Merrimack commercial and manufacturing infrastructure for ONIVYDE®, and generic doxorubicin HCl liposome injection.
“The addition of ONIVYDE® to Ipsen's Oncology portfolio is very important, first and foremost for patients with pancreatic cancer across the U.S., as there are limited approved therapies,” said Cynthia Schwalm, Executive Vice President and President, North American Commercial Operations, Ipsen. “Together with our experienced commercial and medical teams and the legacy we have gained through the acquisition of ONIVYDE®, we are confident in our ability to meet the growing needs of these patients.”
Along with this acquisition, Ipsen will continue to advance the clinical development program for ONIVYDE®.
Financial terms of the acquisition include an upfront cash payment of $575 million to Merrimack Pharmaceuticals, and up to $450 million upon the approval of potential additional indications for ONIVYDE® in the U.S.
About Pancreatic Cancer
Pancreatic cancer is a rare and
deadly disease with approximately 338,0003 new patients
diagnosed globally each year, approximately 50,000 of which are
in the United States4. More than half are diagnosed
with metastatic disease, which has an overall 5-year survival rate of
less than three percent4, and often rapidly progresses during
or shortly after receiving chemotherapy5. Pancreatic cancer
is the 3rd leading cause of cancer-related death in the United States,
surpassing breast cancer.4 It is expected to become the 2nd
leading cause of cancer-related death in the U.S. by the year 2030,
surpassing colorectal cancer.4,6
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, SN-38. ONIVYDE® was approved by
the U.S. FDA in combination with fluorouracil and leucovorin for the
treatment of patients with metastatic adenocarcinoma of the pancreas
after disease progression following gemcitabine-based therapy. For full
prescribing information, including Boxed WARNING, please visit www.ONIVYDE.com.
IMPORTANT SAFETY INFORMATION - UNITED STATES
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.
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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
ONIVYDE® can cause severe or life-threatening neutropenia and fatal neutropenic sepsis. In a clinical study, the incidence of fatal neutropenic sepsis was 0.8% among patients receiving ONIVYDE®, occurring in 1/117 patients in the ONIVYDE®/5-FU/LV arm and 1/147 patients receiving ONIVYDE® as a single agent. Severe or life-threatening neutropenia occurred in 20% of patients receiving ONIVYDE®/5-FU/LV vs 2% of patients receiving 5-FU/LV. Grade 3/4 neutropenic fever/neutropenic sepsis occurred in 3% of patients receiving ONIVYDE®/5-FU/LV, and did not occur in patients receiving 5-FU/LV.
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
ONIVYDE® can cause severe and life-threatening diarrhea. Do not administer ONIVYDE® to patients with bowel obstruction. Severe and life-threatening late-onset (onset > 24 hours after chemotherapy) and early-onset diarrhea (onset =24 hours after chemotherapy, sometimes with other symptoms of cholinergic reaction) were observed. An individual patient may experience both early- and late-onset diarrhea.
In a clinical study, Grade 3/4 diarrhea occurred in 13% of patients receiving ONIVYDE®/5-FU/LV vs 4% receiving 5-FU/LV. Grade 3/4 late-onset diarrhea occurred in 9% of patients receiving ONIVYDE®/5-FU/LV vs 4% in patients receiving 5-FU/LV; the incidences of early-onset diarrhea were 3% and no Grade 3/4 incidences, respectively. Of patients receiving ONIVYDE®/5-FU/LV, 34% received loperamide for late-onset diarrhea and 26% received atropine for early-onset diarrhea.
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
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 1 month after ONIVYDE® treatment.
ADVERSE REACTIONS
- The most common (=20%) adverse reactions in which patients receiving ONIVYDE®/5-FU/LV experienced a =5% higher incidence of any Grade vs the 5-FU/LV arm, were diarrhea (any 59%, 26%; severe 13%, 4%) (early diarrhea [any 30%, 15%; severe 3%, 0%], late diarrhea [any 43%, 17%; severe 9%, 4%]), fatigue/asthenia (any 56%, 43%; severe 21%, 10%), vomiting (any 52%, 26%; severe 11%, 3%), nausea (any 51%, 34%; severe 8%, 4%), decreased appetite (any 44%, 32%; severe 4%, 2%), stomatitis (any 32%, 12%; severe 4%, 1%), pyrexia (any 23%, 11%; severe 2%, 1%).
- Of less common (< 20%) adverse reactions, patients receiving ONIVYDE®/5-FU/LV who experienced Grade 3/4 adverse reactions at a =2% higher incidence of Grade 3/4 toxicity vs the 5-FU/LV arm, respectively, were sepsis (3%, 1%), neutropenic fever/neutropenic sepsis (3%, 0%), gastroenteritis (3%, 0%), intravenous catheter-related infection (3%, 0%), weight loss (2%, 0%), and dehydration (4%, 2%).
- The laboratory abnormalities in which patients receiving ONIVYDE®/5-FU/LV experienced a =5% higher incidence vs the 5-FU/LV arm, were anemia (any 97%, 86%; severe 6%, 5%), lymphopenia (any 81%, 75%; severe 27%, 17%), neutropenia (any 52%, 6%; severe 20%, 2%), thrombocytopenia (any 41%, 33%; severe 2%, 0%), increased alanine aminotransferase (any 51%, 37%; severe 6%, 1%), hypoalbuminemia (any 43%, 30%; severe 2%, 0%), hypomagnesemia (any 35%, 21%; severe 0%, 0%), hypokalemia (any 32%, 19%; severe 2%, 2%), hypocalcemia (any 32%, 20%; severe 1%, 0%), hypophosphatemia (any 29%, 18%; severe 4%, 1%), hyponatremia (any 27%, 12%; severe 5%, 3%), increased creatinine (any 18%, 13%; severe 0%, 0%).
- ONIVYDE® can cause cholinergic reactions manifesting as rhinitis, increased salivation, flushing, bradycardia, miosis, lacrimation, diaphoresis, and intestinal hyperperistalsis with abdominal cramping and early-onset diarrhea. Grade 1/2 cholinergic symptoms other than early diarrhea occurred in 12 (4.5%) ONIVYDE®-treated patients.
- Infusion reactions, consisting of rash, urticaria, periorbital edema, or pruritus, occurring on the day of ONIVYDE® administration were reported in 3% of patients receiving ONIVYDE® or ONIVYDE®/5-FU/LV.
- The most common serious adverse reactions (=2%) of ONIVYDE® were diarrhea, vomiting, neutropenic fever or neutropenic sepsis, nausea, pyrexia, sepsis, dehydration, septic shock, pneumonia, acute renal failure, and thrombocytopenia.
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
Advise pregnant women of the potential risk to a fetus. Advise males with female partners of reproductive potential to use effective contraception during and for 4 months after ONIVYDE® treatment.
Lactation
Advise nursing women not to breastfeed during and
for 1 month after ONIVYDE® treatment.
Pediatric
Safety and effectiveness of ONIVYDE®
have not been established in pediatric patients.
DOSAGE AND ADMINISTRATION
The recommended dose of ONIVYDE® is 70 mg/m2 intravenous (IV) infusion over 90 minutes every 2 weeks, administered prior to LV and 5-FU. The recommended starting dose of ONIVYDE® in patients known to be homozygous for the UGT1A1*28 allele is 50 mg/m2 administered by IV infusion over 90 minutes. There is no recommended dose of ONIVYDE® for patients with serum bilirubin above the upper limit of normal. Premedicate with a corticosteroid and an anti-emetic 30 minutes prior to ONIVYDE®. Withhold ONIVYDE® for Grade 3/4 adverse reactions. Resume ONIVYDE® with reduced dose once adverse reaction recovered to =Grade 1. Discontinue ONIVYDE® in patients who experience a severe hypersensitivity reaction and in patients with a confirmed diagnosis of ILD.
Do not substitute ONIVYDE® for other drugs containing irinotecan HCl.
Please see full U.S. Prescribing Information for ONIVYDE®.
About Generic Doxorubicin HCl Liposome Injection
Generic
doxorubicin HCl Liposome Injection is currently being evaluated by the
U.S. Food and Drug Administration (FDA) for the potential treatment of
ovarian cancer, multiple myeloma and Kaposi's sarcoma. Teva retains the
worldwide commercial rights for this product, and Ipsen will be eligible
to receive milestones and shared profits from potential sales.
About Ipsen in North America
Ipsen Biopharmaceuticals, Inc.
is the US affiliate of Ipsen, a global specialty driven pharmaceutical
group. The US head office is located in Basking Ridge, New Jersey. Ipsen
Biopharmaceuticals Canada, Inc. is an integrated business unit within
North America and has its head office located in Mississauga, Ontario.
Ipsen Bioscience, Inc., the Ipsen US research and development center
focused on peptide research in oncology and endocrinology, is located in
Cambridge, Massachusetts. At Ipsen Bioscience, we focus on creating a
highly cooperative and passionate R&D organization through partnerships,
innovation, and continuous learning to effectively deliver new
treatments for patients. At Ipsen Biopharmaceuticals, we focus our
resources, investments, and energy on discovering, developing, and
commercializing new therapeutic options for oncologic, neurologic, and
endocrine diseases. For more information on Ipsen in North America,
please visit www.ipsenus.com
or www.ipsen.ca.