– 44% of patients achieved a response and
nearly half (48%) maintained disease control at week 12 (efficacy
as secondary endpoint) –
– Treatment emergent adverse events Grade 3 or
higher were reported by 10 of 25 patients (safety as primary
endpoint) –
Regulatory News:
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the full release here:
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Ipsen (Euronext: IPN; ADR: IPSEY) and Servier
announced today initial safety and efficacy data from Part 1 of the
Phase II/III RESILIENT study of investigational liposomal
irinotecan (ONIVYDE®) in patients with small cell lung cancer
(SCLC) who progressed following a first-line platinum-based
regimen. The results, which included preliminary safety and
efficacy data, were presented as an oral presentation at the IASLC
2019 World Conference on Lung Cancer hosted by the International
Association for the Study of Lung Cancer in Barcelona, 7-10
September 2019.
The RESILIENT (NCT03088813) trial is a randomized, open-label
two-part Phase II/III study assessing the safety, tolerability and
efficacy of investigational liposomal irinotecan as a monotherapy
for SCLC patients who have progressed on or after a first-line
platinum-based regimen. The trial is being conducted in two parts.
Part 1 includes dose-finding and dose-escalation analyses to
determine the appropriate dose of study drug where the primary
endpoints are safety and tolerability. Part 2 has just been
initiated with the first patients randomized and will focus on
efficacy assessments versus the current standard of care,
topotecan, including progression-free survival (PFS) and overall
survival (OS).
“Immunotherapies and combination therapies have proven
beneficial in the first-line setting, but despite these advances,
many small cell lung cancer patients rapidly relapse due to the
aggressive nature of the disease,” said Luis G. Paz-Ares, M.D.,
Ph.D., lead investigator and chief physician, Hospital
Universitario 12 de Octubre, Madrid. “While the current standard of
care in the second-line setting can extend survival, treatment
toxicity has prevented some patients from receiving the full
recommended dose. There is a clear need for more treatment options
that may give more patients the chance to remain on therapy. It is
positive that the RESILIENT trial will continue to investigate
this.”
ONIVYDE® (liposomal irinotecan) is a topoisomerase inhibitor
featuring a liposomal formulation of irinotecan that is designed to
prolong its circulation before conversion to its active form. This
unique mechanism of delivery was evaluated in the NAPOLI-1 Phase
III study, which led to the U.S. Food and Drug Administration (FDA)
and European Medicines Agency (EMA) approval of ONIVYDE® in
combination with fluorouracil (5-FU) and leucovorin (LV) for the
treatment of metastatic pancreatic cancer following
gemcitabine-based therapy. ONIVYDE® is not indicated as a single
agent for the treatment of patients with metastatic adenocarcinoma
of the pancreas.
“ONIVYDE® has been proven to help many metastatic pancreatic
cancer patients whose disease has progressed following
gemcitabine-based therapy to live longer,” said Yan Moore, M.D.,
Ipsen’s Senior Vice President, Head of Oncology Therapeutic Area.
“By applying this research to other hard-to-treat-cancers, like
small cell lung cancer, we aim to evaluate the potential benefit
investigational ONIVYDE® may bring to patients who otherwise would
have limited treatment options.”
“The data presented today shows that further research is
warranted, and we look forward to working with Ipsen and our
investigators to understand the full potential of bringing new
treatment options to small cell lung cancer patients,” said Patrick
Therasse, M.D., Ph.D., Head of Servier Research and Development
Oncology.
Part 1 of the study enrolled 30 patients (median age = 60
(48-73) years) who were treated every two weeks for >12 weeks,
with tumor assessments taking place every six weeks. During the
dose-finding phase, five patients received liposomal irinotecan
85mg/m2. This dose was deemed not tolerable due to dose limiting
toxicity. An additional 12 patients received liposomal irinotecan
70mg/m2, which was deemed tolerable. Thirteen more patients were
enrolled in the dose expansion phase of the study at this dose. As
of the May 8, 2019 data cut off, a total of 25 patients had
received liposomal irinotecan 70mg/m2.
Safety Results:
- Liposomal irinotecan 70mg/m2 was generally well-tolerated with
Grade 3 or higher treatment emergent adverse events (TEAEs)
reported by 10 out of 25 patients.
- Diarrhea was the most common Grade 3 gastrointestinal TEAE
(n=5).
- Hematologic Grade 3 or higher TEAEs included neutropenia (n=4)
anemia (n=2) and thrombocytopenia (n=2).
- One reported instance of Grade 3 or higher fatigue.
Efficacy Results:
- Best overall response (partial response plus stable disease)
was 72% with an objective response rate of 44%.
- 44% (11/25) of patients achieved a partial response with 68% of
patients (17/25) experiencing tumor shrinkage.
- 48% of patients maintained disease control at 12-weeks
(DCR12wks PR+SD).
- Data for OS and PFS are still maturing.
ABOUT ONIVYDE® (irinotecan liposome injection)
Ipsen has exclusive commercialization rights for the current and
potential future indications for ONIVYDE® in the U.S. 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 RESILIENT Study
The Phase II/III, randomized, open-label, RESILIENT study is
designed to assess the safety, tolerability and efficacy of
investigational ONIVYDE® versus topotecan in patients with small
cell lung cancer who have progressed on or after platinum-based
first-line therapy. The study is enrolling up to 486 patients at 34
sites across the United States, Spain, Germany, France, Taiwan and
Australia.
The study is being conducted in two parts:
- Part 1: Open-label dose-finding study of ONIVYDE®; 30 patients
have been enrolled in Part 1 of the study.
- Part 2: A randomized, efficacy study of ONIVYDE® versus IV
topotecan; approximately 450 patients will be enrolled in Part
2.
The study’s primary endpoint is overall survival defined as the
time from randomization to date of death. Secondary assessments
include progression-free survival, objective response rate,
proportion of patients with symptom improvement and incidence of
treatment-emergent adverse events, serious adverse events and
laboratory abnormalities. The rate of development of CNS
metastases, and biomarkers associated with efficacy and toxicity
will be explored. For more information visit clinicaltrials.gov and
use identifier NCT03088813.
About Ipsen
Ipsen is a global specialty-driven biopharmaceutical company
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
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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
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Use of the words "believes", "anticipates" and "expects" and
similar expressions are intended to identify forward-looking
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events, including regulatory filings and determinations, and the
outcome of this study or other studies. Moreover, the targets
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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
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The Group expressly disclaims any obligation or undertaking to
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Document available on its website (www.ipsen.com).
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version on businesswire.com: https://www.businesswire.com/news/home/20190908005027/en/
Ipsen Media Relations Christian Marcoux, M.Sc. SVP,
Global Communications +33 (0) 1 58 33 67 94
christian.marcoux@ipsen.com
Kelly Blaney Vice President, Global 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
+33 (0)1 55 72 40 21 / + 33 (0)7 84 28 76 13
Jean-Clément VERGEAU media@servier.com +33 (0)1 55 72 46 16 /
+33 (0)6 79 56 75 96
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