PARIS–(BUSINESS WIRE)–Regulatory News:
Ipsen (Euronext: IPN; ADR: IPSEY) today announced that new data from
clinical studies on investigational uses of cancer medicines
cabozantinib (Cabometyx®), liposomal irinotecan (Onivyde®),
and lanreotide autogel (Somatuline®, marketed as Somatuline
Depot® in the United States) will be presented at the 2019
American Society of Clinical Oncology (ASCO) Annual Meeting. The meeting
takes place in Chicago, Illinois, U.S., 31 May–4 June 2019; data
featuring Ipsen medicines includes:
-
New data from the Phase 3 CELESTIAL trial on the association of
adverse events with efficacy outcomes for cabozantinib in patients
with advanced hepatocellular carcinoma -
Overview of the Phase 3 COSMIC-312 trial of cabozantinib in
combination with atezolizumab vs sorafenib in patients with advanced
hepatocellular carcinoma who have not received previous systemic
anticancer therapy -
First Phase 2 data from the CaboGIST study (trial 1317) from
the European Organization for Research and Treatment of Cancer on the
activity and safety of cabozantinib in patients with metastatic
gastrointestinal stromal tumor after failure of imatinib and sunitinib -
Preliminary results from the RESILIENT study of liposomal
irinotecan injection in patients with small cell lung cancer -
Results from a Phase 2 multicenter study of lanreotide autogel
in the treatment of clinical symptoms associated with inoperable
malignant intestinal obstruction
“At Ipsen, patients inspire and drive us to tackle some of the most
difficult-to-treat cancers, particularly where few effective options
exist. ASCO gives us the opportunity to share the progress we have made
in our mission of developing and delivering therapeutic solutions that
meet the real needs of patients and may help improve their lives,” said
Dr. Alexandre Lebeaut, Ipsen’s Executive Vice President, R&D, and Chief
Scientific Officer. “With our continued clinical programs and
collaborations, we are making strides in renal, liver and small cell
lung cancers and other cancers with high unmet need, and we look forward
to continuing to advance these programs.”
Follow Ipsen on Twitter via @IpsenGroup and @IpsenUS and keep up to date
with ASCO 2019 congress news and updates by using the hashtag #ASCO19.
Overview of key Ipsen presentations at ASCO 2019:
| Medicine | Abstract title |
Abstract number/timing |
||||
|
Cabometyx® (cabozantinib) |
Phase 3 (COSMIC-311) randomized, double-blind, placebo- controlled |
Abstract TPS6097 Poster 82a – Category: Head and Neck Cancer;
|
||||
|
Association of adverse events (AEs) with efficacy outcomes for |
Abstract 4088 Poster 193 – Category: Gastrointestinal |
|||||
|
Phase 3 (COSMIC-312) study of cabozantinib (C) in combination with |
Abstract TPS4157 Poster 254a – Category: Gastrointestinal
|
|||||
|
Onivyde® (nal- |
RESILIENT: Study of Irinotecan Liposome Injection (nal-IRI) in |
Abstract 8562 Poster 318 – Category: Lung Cancer—Non-Small Cell |
||||
|
Somatuline® Autogel® |
Efficacy and Safety of Lanreotide Autogel (LAN) 120 mg in |
Abstract 4118 Poster 223 – Category: Gastrointestinal |
Overview of key investigator sponsored study presentations featuring
Ipsen medicines at ASCO 2019:
| Medicine | Abstract title |
Abstract number/timing |
||||
|
Cabometyx® (cabozantinib) |
Activity and safety of cabozantinib in patients with metastatic
|
Abstract 11006 Oral: Category: Sarcoma; Monday, 3 June, 10:00 AM – |
||||
|
PDIGREE: An adaptive Phase 3 trial of PD-inhibitor nivolumab and
|
Abstract TPS4596 Poster 417a – Category: Genitourinary |
|||||
|
Prognostic value of sequential 18F- FDG + Na18F PET/CT (NaF+FDG
|
Abstract 4544 Poster 370 – Category: Genitourinary (Nonprostate) |
|||||
|
Circulating tumor cell (CTC) enumeration in patients (pts) with |
Abstract 4555 Poster 381 – Category: Genitourinary (Nonprostate) |
|||||
|
Correlates of overall survival (OS) in metastatic vs. primary
|
Abstract 9506 – Oral: Category: Melanoma/Skin Cancers; Poster – |
|||||
|
Onivyde® (nal- |
A multicenter phase Ib/II study of nalirinotecan, 5fluouracil and |
Abstract TPS4154 Poster 252b – Category: Gastrointestinal |
ABOUT IPSEN PRODUCTS
This press release mentions
investigational uses of Ipsen products. Product indications and
approvals for use vary by jurisdiction; please see SmPC/PI for full
indications and safety information.
ABOUT ONIVYDE® (irinotecan liposome
injection)
ONIVYDE is an encapsulated formulation of irinotecan
available as a 43 mg/10 mL single dose vial. This liposomal form is
designed to increase length of tumor exposure to both irinotecan and its
active metabolite, SN- 38.
On April 3, 2017, Ipsen completed the acquisition from Merrimack
Pharmaceuticals of ONIVYDE and gained exclusive commercialization rights
for the current and potential future indications for ONIVYDE in the US.
Servier1 is responsible for the development and
commercialization of ONIVYDE outside of the U.S. and Taiwan under an
exclusive licensing agreement with Ipsen Biopharm Ltd.
ONIVYDE is approved by the U.S. FDA 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.
1 Servier is an international pharmaceutical company,
governed by a non-profit foundation, with headquarters in the Paris
metropolitan area.
IMPORTANT SAFETY INFORMATION – UNITED STATES
BOXED
WARNINGS: 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 5-FU and 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 I 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
Special Populations
-
Pregnancy and Reproductive Potential: See WARNINGS & PRECAUTIONS.
Advise males with female partners of reproductive potential to use
condoms during and for 4 months after ONIVYDE treatment -
Lactation: Advise nursing women not to breastfeed during and for 1
month after ONIVYDE treatment
Please see full U.S. Prescribing Information for ONIVYDE®.
ABOUT CABOMETYX® (cabozantinib)
CABOMETYX® is not marketed by Ipsen in the U.S.
CABOMETYX® 20mg, 40mg and 60mg film-coated unscored tablets
Active ingredient: Cabozantinib (S)-malate 20mg, 40mg and 60mg
Other components: Lactose
Indications: In the U.S., CABOMETYX tablets are approved for the
treatment of patients with advanced RCC and for the treatment of
patients with hepatocellular carcinoma (HCC) who have been previously
treated with sorafenib.
CABOMETYX tablets are also approved in: the European Union, Norway,
Iceland, Australia, Switzerland, South Korea, Canada, Brazil and Taiwan
for the treatment of advanced RCC in adults who have received prior
VEGF-targeted therapy; in the European Union for previously untreated
intermediate- or poor-risk advanced RCC; in Canada for adult patients
with advanced RCC who have received prior VEGF targeted therapy; and in
the European Union, Norway and Iceland for HCC in adults who have
previously been treated with sorafenib.
CABOMETYX is not indicated for previously untreated advanced HCC.
Dosage and Administration: The recommended dose of CABOMETYX®
is 60 mg once daily. Treatment should continue until the patient is no
longer clinically benefiting from therapy or until unacceptable toxicity
occurs. Management of suspected adverse drug reactions may require
temporary interruption and/or dose reduction of CABOMETYX®
therapy. For dose modification, please refer to full SmPC. CABOMETYX®
is for oral use. The tablets should be swallowed whole and not crushed.
Patients should be instructed to not eat anything for at least 2 hours
before through 1 hour after taking CABOMETYX®.
Contraindications: Hypersensitivity to the active substance or to
any of the excipients listed in the SmPC.
Special Warnings and Precautions For Use:
Monitor closely
for toxicity during first 8 weeks of therapy. Events that generally have
early onset include hypocalcemia, hypokalemia, thrombocytopenia,
hypertension, palmar-plantar erythrodysaesthesia syndrome (PPES),
proteinuria, and gastrointestinal (GI) events.
Perforations and fistulas: serious gastrointestinal perforations
and fistulas, sometimes fatal, have been observed with cabozantinib.
Patients with inflammatory bowel disease, GI tumor infiltration or
complications from prior GI surgery should be evaluated prior to therapy
and monitored; if perforation and unmanageable fistula occur,
discontinue cabozantinib.
Thromboembolic events: use with caution in patients with a
history of or risk factors for thromboembolism; discontinue if acute
myocardial infarction (MI) or other significant arterial thromboembolic
complication occurs.
Hemorrhage: not recommended for patients that have or are at risk
of severe hemorrhage.
Wound complications: treatment should be stopped at least 28 days
prior to scheduled surgery (including dental).
Hypertension: monitor blood pressure (BP); reduce with persistent
hypertension and discontinue should uncontrolled hypertension or
hypertensive crisis occur.
Palmar-plantar erythrodysesthesia (PPES): interrupt treatment if
severe PPES occurs.
Proteinuria: discontinue in patients with nephrotic syndrome.
Reversible posterior leukoencephalopathy syndrome (RPLS):
discontinue in patients with RPLS.
QT interval prolongation: use with caution in patients with a
history of QT prolongation, those on antiarrhythmics or with
pre-existing cardiac disease.
Excipients: do not use in patients with hereditary problems of
galactose intolerance, Lapp lactase deficiency or glucose-galactose
malabsorption.
Drug Interactions: Cabozantinib is a CYP3A4 substrate. Potent
CYP3A4 inhibitors may result in an increase in cabozantinib plasma
exposure (e.g. ritonavir, itraconazole, erythromycin, clarithromycin,
grapefruit juice). Coadministration with CYP3A4 inducers may result in
decreased cabozantinib plasma exposure (e.g. rifampicin, phenytoin,
carbamazepine, phenobarbital, St John’s Wort). Cabozantinib may increase
the plasma concentration of P-glycoprotein substrates (e.g.
fexofenadine, aliskiren, ambrisentan, dabigatran etexilate, digoxin,
colchicine, maraviroc, posaconazole, ranolazine, saxagliptin,
sitagliptin, talinolol, tolvaptan). MRP2 inhibitors may increase
cabozantinib plasma concentrations (e.g. cyclosporine, efavirenz,
emtricitabine). Bile salt sequestering agents may impact absorption or
reabsorption resulting in potentially decreased cabozantinib exposure.
No dose adjustment when co-administered with gastric pH modifying
agents. A plasma protein displacement interaction may be possible with
warfarin. INR values should be monitored in such a combination.
Women of childbearing potential/contraception in males and females:
Ensure effective measures of contraception (oral contraceptive plus a
barrier method) in male and female patients and their partners during
therapy and for at least 4 months after treatment.
Pregnancy and lactation: CABOMETYX should not be used during pregnancy
unless the clinical condition of the woman requires treatment. Lactation
– discontinue breast-feeding during and for at least 4 months after
completing treatment. Drive and use machines: Caution is recommended
Adverse Reactions:
The most common serious adverse reactions
are hypertension, diarrhea, PPES, pulmonary embolism, fatigue and
hypomagnesaemia. Very common (>1/10): anemia, lymphopenia neutropenia,
thrombocytopenia, hypothyroidism, dehydration, decreased appetite,
hyperglycemia, hypoglycemia, hypophosphatasemia, hypoalbuminemia,
hypomagnesaemia, hyponatremia, hypokalemia, hyperkalemia, hypocalcemia,
hyperbilirubinemia, peripheral sensory neuropathy, dysgeusia, headache,
dizziness, hypertension, dysphonia, dyspnea, cough, diarrhea, nausea,
vomiting, stomatitis, constipation, abdominal pain, dyspepsia, oral
pain, dry mouth, PPES, dermatitis acneiform, rash, rash maculopapular,
dry skin, alopecia, hair color change, pain in extremity, muscle spasms,
arthralgia, proteinuria, fatigue, mucosal inflammation, asthenia, weight
decreased, serum ALT, AST, and ALP increased, blood bilirubin increased,
creatinine increased, triglycerides increased, white blood cell
decreased, GGT increased, amylase increased, blood cholesterol
increased, lipase increased. Common (>1/100 to <1/10): abscess,
tinnitus, pulmonary embolism, pancreatitis, abdominal pain upper,
gastro-esophageal reflux disease, hemorrhoids, pruritus, peripheral
edema, wound complications. Uncommon (>1/1000 to <1/100): convulsion,
anal fistula, hepatitis cholestatic, osteonecrosis of the jaw. Selected
adverse events: GI perforation, fistulas, hemorrhage, RPLS.
Prescribers should consult the SPC in relation to other adverse
reactions.
For more information, see the regularly updated registered product
information on the European Medicine Agency www.ema.europa.eu
ONIVYDE is a registered trademark of Ipsen Biopharm Limited.
XERMELO® is not marketed by Ipsen in the United States. The
approved indications may vary by country. CABOMETYX® is
marketed by Exelixis, Inc. in the United States. Ipsen has exclusive
rights for the commercialization and further clinical development of
CABOMETYX® outside of the United States and Japan.
ABOUT SOMATULINE® (lanreotide)
Indications
SOMATULINE®
DEPOT (lanreotide) is a somatostatin analog indicated for:
-
the treatment of adult patients with unresectable, well- or
moderately-differentiated, locally advanced or metastatic
gastroenteropancreatic neuroendocrine tumors (GEP-NETs) to improve
progression-free survival; and -
the treatment of adults with carcinoid syndrome; when used, it reduces
the frequency of short acting somatostatin analog rescue therapy.
IMPORTANT SAFETY INFORMATION
Contraindications
-
SOMATULINE DEPOT is contraindicated in patients with hypersensitivity
to lanreotide. Allergic reactions (including angioedema and
anaphylaxis) have been reported following administration of lanreotide.
Warnings and Precautions
-
Cholelithiasis and Gallbladder Sludge
-
SOMATULINE DEPOT may reduce gallbladder motility and lead to
gallstone formation. - Periodic monitoring may be needed.
-
If complications of cholelithiasis are suspected, discontinue
SOMATULINE DEPOT and treat appropriately
-
SOMATULINE DEPOT may reduce gallbladder motility and lead to
-
Hypoglycemia or Hyperglycemia
-
Patients treated with SOMATULINE DEPOT may experience hypoglycemia
or hyperglycemia. -
Blood glucose levels should be monitored when SOMATULINE DEPOT
treatment is initiated, or when the dose is altered, and
antidiabetic treatment should be adjusted accordingly.
-
Patients treated with SOMATULINE DEPOT may experience hypoglycemia
-
Cardiovascular Abnormalities
- SOMATULINE DEPOT may decrease heart rate.
-
In patients without underlying cardiac disease, SOMATULINE DEPOT
may lead to a decrease in heart rate without necessarily reaching
the threshold of bradycardia. -
In patients suffering from cardiac disorders prior to treatment,
sinus bradycardia may occur. Care should be taken when initiating
treatment in patients with bradycardia.
Most Common Adverse Reactions
-
GEP-NETs: Adverse reactions in >10% of patients who received
SOMATULINE DEPOT were abdominal pain (34%), musculoskeletal pain
(19%), vomiting (19%), headache (16%), injection site reaction (15%),
hyperglycemia (14%), hypertension (14%), and cholelithiasis (14%).
-
Carcinoid Syndrome: Adverse reactions occurring in the
carcinoid syndrome trial were generally similar to those in the
GEP-NET trial. Adverse reactions in ≥5% of patients who received
SOMATULINE DEPOT and at least 5% greater than placebo were headache
(12%), dizziness (7%) and muscle spasm (5%).
Drug Interactions: SOMATULINE DEPOT may decrease the absorption
of cyclosporine (dosage adjustment may be needed); increase the
absorption of bromocriptine; and require dosage adjustment for
bradycardia-inducing drugs (e.g., beta-blockers).
Special Populations
-
Lactation: Advise women not to breastfeed during treatment and for 6
months after the last dose. -
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 click here for the full Prescribing Information and Patient
Information.
About Ipsen
Ipsen is a global specialty-driven
biopharmaceutical group focused on innovation and specialty care. The
group develops and commercializes innovative medicines in three key
therapeutic areas – Oncology, Neuroscience and Rare Diseases. Its
commitment to Oncology is exemplified through its growing portfolio of
key therapies for prostate cancer, neuroendocrine tumors, renal cell
carcinoma and pancreatic cancer. Ipsen also has a well-established
Consumer Healthcare business. With total sales over €2.2 billion in
2018, Ipsen sells more than 20 drugs in over 115 countries, with a
direct commercial presence in more than 30 countries. Ipsen’s R&D is
focused on its innovative and differentiated technological platforms
located in the heart of the leading biotechnological and life sciences
hubs (Paris-Saclay, France; Oxford, UK; Cambridge, US). The Group has
about 5,700 employees worldwide. Ipsen is listed in Paris (Euronext:
IPN) and in the United States through a Sponsored Level I American
Depositary Receipt program (ADR: IPSEY). For more information on Ipsen,
visit www.ipsen.com.
Forward Looking Statement
The forward-looking statements,
objectives and targets contained herein are based on the Group’s
management strategy, current views and assumptions.
Contacts
Christian Marcoux
Corporate Communications
+33 (0) 1 58 33 67
94
christian.marcoux@ipsen.com
Kelly Blaney
Corporate Communications
+44 (0) 7903 402275
kelly.blaney@ipsen.com
Financial Community
Eugenia Litz
Vice President, Investor
Relations
+44 (0) 1753 627721
eugenia.litz@ipsen.com
Myriam Koutchinsky
Investor Relations Manager
+33 (0)1 58 33
51 04
myriam.koutchinsky@ipsen.com