– Treatment emergent adverse events Grade 3 or
higher were reported by 20 of 32 patients from the 50/60 dose
pooled patient analysis; no patient reported Grade 3 or higher
fatigue or peripheral neuropathy (primary endpoint) –
– Approximately three quarters of patients
(71.9%) achieved disease control at week 16, while 34% had a
response (secondary endpoint) –
Regulatory News:
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Ipsen (Euronext: IPN; ADR: IPSEY) and Servier announced today
preliminary data from the Phase 1/2 study of the investigational
use of liposomal irinotecan (ONIVYDE®) in combination with 5-
fluorouracil/leucovorin (5-FU/LV) and oxaliplatin (OX) in study
patients with previously untreated metastatic pancreatic ductal
adenocarcinoma cancer (PDAC) at the ESMO 21st World Congress on
Gastrointestinal Cancer in Barcelona, Spain, 3–6 July 2019. The
results, which were presented as a short oral presentation,
included preliminary safety and efficacy data from an ongoing
multicenter, open-label, dose-escalation study, which aims to
determine the maximum tolerated dose and the recommended dose to be
used in future clinical studies.
“Pancreatic cancer is aggressive and difficult to treat. With
most patients going undiagnosed until the disease has spread and
the prognosis is poor, some physicians may be reluctant to consider
novel treatment options,” said Zev Wainberg, M.D., lead
investigator and associate professor of medicine, University of
California Los Angeles. “It’s critical that physicians have more
treatment options for their patients, particularly in the first
line of therapy.”
“ONIVYDE® is the first and only FDA and EMA approved second-line
treatment for metastatic pancreatic cancer following
gemcitabine-based therapy, and the initial data presented today
provides a first look into the use of this investigational therapy
earlier in the treatment sequence,” said Yan Moore, M.D., Ipsen’s
Senior Vice President, Head of Oncology Therapeutic Area. “We look
forward to further analyses of these early data, with the aim of
evolving the standard of care in metastatic pancreatic cancer.”
“It is vitally important to advance the research of new
treatment approaches for pancreatic cancer patients, a goal Servier
shares with Ipsen,” said Patrick Therasse, Head of Servier Research
and Development Oncology.
ONIVYDE® is a topoisomerase inhibitor indicated in combination
with 5-FU/LV for metastatic pancreatic cancer after disease
progression following gemcitabine-based therapy. The ongoing Phase
1/2, open-label trial (NCT02551991) was designed to assess the
safety, tolerability and dose-limiting toxicities (DLTs) of the
study drug, liposomal irinotecan, in combination with 5-FU/LV and
OX, known as NAPOX, for the first-line treatment of study
participants with metastatic pancreatic cancer. Secondary
objectives were to assess clinical efficacy, defined by overall
response rate (ORR), disease control rate (DCR) and best overall
response (BOR). Preliminary analyses of median progression-free
survival and median overall survival were not mature enough for
evaluation.
As of the 19 February 2019 data cut off, a total of 56 study
patients (median age = 58 (39-76) years) were enrolled and dosed at
15 sites across the US, Spain and Australia. The interim analysis
was conducted after all study participants in the four dose
exploration cohorts had completed their second scheduled tumor
evaluation at 16 weeks. Study participants from the Part 1A–cohort
B (n=7) dose exploration phase and study participants from the Part
1B–dose expansion phase (n=25) received the selected dose level of
liposomal irinotecan 50 mg/m2 [free-base equivalent; FBE], LV 400
mg/m2, 5-FU 2400 mg/m2, and OX 60 mg/m2. These 32 patients made up
the pooled population (PP) analysis (n=29 mPDAC; n=3 locally
advanced pancreatic PDAC).
Safety Results:
- No reported Grade 3 or higher fatigue or peripheral
neuropathy.
- One study participant in the Part 1A–cohort B dose exploration
phase reported a DLT (febrile neutropenia).
- Treatment emergent adverse events (TEAEs) Grade 3 or higher
were reported by 20 of 32 study patients in the 50/60 PP and
included: neutropenia (n=9); febrile neutropenia (n=4); hypokalemia
(n=4); diarrhea (n=3); nausea (n=3); anemia (n=2); vomiting
(n=2).
- Four study patients in the 50/60 PP reported TEAEs leading to
discontinuation (n=4/32), with 23 study patients requiring dose
adjustment due to AEs.
- At data cut-off, 15/32 study patients in the 50/60 PP remained
on treatment.
Efficacy Results:
- BOR (Best Overall Response) was: one complete response (CR;
study participant diagnosed with locally advanced Stage III
disease), 10 partial responses (PR) in 31.3% (10/32) and 15 stable
diseases (SD) in 46.9% (15/32) (sum of CR+PR+SD = 81.3%).
- 71.9% (23/32) of study patients in the 50/60 PP achieved
disease control at 16 weeks.
- Overall, 34% of study patients had a response.
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.
Ipsen has exclusive commercialization rights for the current and
potential future indications for ONIVYDE® in the US. Servier is
responsible for the development and commercialization of ONIVYDE®
outside of the U.S. and Taiwan under an exclusive licensing
agreement with Ipsen.
ONIVYDE® is approved by the FDA and the EMA 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.
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 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
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 the Phase 1/2 Study The Phase 1/2, open-label,
comparative trial is designed to assess the safety, tolerability
and dose-limiting toxicities of irinotecan liposomal injection
(ONIVYDE®) in combination with 5- fluorouracil/leucovorin (5-FU/LV)
and oxaliplatin (OX) as a first-line treatment for metastatic
pancreatic ductal adenocarcinoma cancer patients. The study has
enrolled 56 patients at 15 sites across the United States, Spain
and Australia. It is being conducted in two parts:
- Part 1a: a safety run-in as initial dose exploration
- Part 1b: dose expansion of the nal-IRI + 5FU/LV + oxaliplatin
regimen
The study’s primary endpoint is safety and tolerability.
Secondary assessments of clinical efficacy include overall response
rate, disease control rate and best overall response. For more
information visit clinicaltrials.gov and use identifier
NCT02551991.
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.
About Servier Servier is an international pharmaceutical
company governed by a non-profit foundation, with its headquarters
in France (Suresnes). With a strong international presence in 149
countries and a turnover of 4.2 billion euros in 2018, Servier
employs 22,000 people worldwide. Entirely independent, the Group
reinvests 25% of its turnover (excluding generics) in research and
development and uses all its profits for development. Corporate
growth is driven by Servier’s constant search for innovation in
five areas of excellence: cardiovascular, immune-inflammatory and
neurodegenerative diseases, cancer and diabetes, as well as by its
activities in high-quality generic drugs. Servier also offers
eHealth solutions beyond drug development. Becoming a key player in
oncology is part of Servier’s long-term strategy. Currently, there
are twelve molecular entities in clinical development in this area,
targeting gastro-intestinal and lung cancers and other solid
tumors, as well as different types of leukemia and lymphomas. This
portfolio of innovative cancer treatments is being developed with
partners worldwide, and covers different cancer hallmarks and
modalities, including cytotoxics, proapoptotics, immune targeted
therapies, to deliver life-changing medicines to patients.
More information: www.servier.com
Find us on Social Media: https://fr.linkedin.com/company/servier
https://fr-fr.facebook.com/Servier/
https://twitter.com/servier?lang=fr
Ipsen’s Forward Looking Statement The forward-looking
statements, objectives and targets contained herein are based on
the Group’s management strategy, current views and assumptions.
Such statements involve known and unknown risks and uncertainties
that may cause actual results, performance or events to differ
materially from those anticipated herein. All of the above risks
could affect the Group’s future ability to achieve its financial
targets, which were set assuming reasonable macroeconomic
conditions based on the information available today. Use of the
words "believes", "anticipates" and "expects" and similar
expressions are intended to identify forward-looking statements,
including the Group’s expectations regarding future events,
including regulatory filings and determinations, and the outcome of
this study or other studies. Moreover, the targets described in
this document were prepared without taking into account external
growth assumptions and potential future acquisitions, which may
alter these parameters. These objectives are based on data and
assumptions regarded as reasonable by the Group. These targets
depend on conditions or facts likely to happen in the future, and
not exclusively on historical data. Actual results may depart
significantly from these targets given the occurrence of certain
risks and uncertainties, notably the fact that a promising product
in early development phase or clinical trial may end up never being
launched on the market or reaching its commercial targets, notably
for regulatory or competition reasons. The Group must face or might
face competition from generic products that might translate into a
loss of market share. Furthermore, the Research and Development
process involves several stages each of which involves the
substantial risk that the Group may fail to achieve its objectives
and be forced to abandon its efforts with regards to a product in
which it has invested significant sums. Therefore, the Group cannot
be certain that favorable results obtained during pre-clinical
trials will be confirmed subsequently during clinical trials, or
that the results of clinical trials will be sufficient to
demonstrate the safe and effective nature of the product concerned.
There can be no guarantees a product will receive the necessary
regulatory approvals or that the product will prove to be
commercially successful. If underlying assumptions prove inaccurate
or risks or uncertainties materialize, actual results may differ
materially from those set forth in the forward-looking statements.
Other risks and uncertainties include but are not limited to,
general industry conditions and competition; general economic
factors, including interest rate and currency exchange rate
fluctuations; the impact of pharmaceutical industry regulation and
health care legislation; global trends toward health care cost
containment; technological advances, new products and patents
attained by competitors; challenges inherent in new product
development, including obtaining regulatory approval; the Group's
ability to accurately predict future market conditions;
manufacturing difficulties or delays; financial instability of
international economies and sovereign risk; dependence on the
effectiveness of the Group’s patents and other protections for
innovative products; and the exposure to litigation, including
patent litigation, and/or regulatory actions. The Group also
depends on third parties to develop and market some of its products
which could potentially generate substantial royalties; these
partners could behave in such ways which could cause damage to the
Group’s activities and financial results. The Group cannot be
certain that its partners will fulfil their obligations. It might
be unable to obtain any benefit from those agreements. A default by
any of the Group’s partners could generate lower revenues than
expected. Such situations could have a negative impact on the
Group’s business, financial position or performance. The Group
expressly disclaims any obligation or undertaking to update or
revise any forward-looking statements, targets or estimates
contained in this press release to reflect any change in events,
conditions, assumptions or circumstances on which any such
statements are based, unless so required by applicable law. The
Group’s business is subject to the risk factors outlined in its
registration documents filed with the French Autorité des Marchés
Financiers. The risks and uncertainties set out are not exhaustive
and the reader is advised to refer to the Group’s 2018 Registration
Document available on its website (www.ipsen.com).
View source
version on businesswire.com: https://www.businesswire.com/news/home/20190705005053/en/
Christian Marcoux, M.Sc. Global Corporate Communications +33 (0)
1 58 33 67 94 christian.marcoux@ipsen.com
Kelly Blaney Global Corporate Communications +44 (0) 7903 402275
kelly.blaney@ipsen.com
Maryann Quinn Director, Product Communications +1-857-529-1151
maryann.quinn@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
Servier media relations Sonia MARQUES: media@servier.com – Tel.:
+33 (0)1 55 72 40 21 / + 33 (0)7 84 28 76 13 Jean-Clément VERGEAU:
media@servier.com – Tel.: +33 (0)1 55 72 46 16 / +33 (0)6 79 56 75
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