- Supplemental New Drug Application
(sNDA) submission based on the NAPOLI 3 Phase III trial1
- Approval would represent expansion
of treatment options in an aggressive and difficult-to-treat cancer
with few treatment options currently available
PARIS, FRANCE,
14 June 2023 – Ipsen (Euronext:
IPN; ADR: IPSEY) today announced that the U.S. Food and Drug
Administration (FDA) has accepted its supplemental new drug
application (sNDA) Onivyde® (irinotecan liposome
injection) plus 5 fluorouracil/leucovorin and oxaliplatin
(NALIRIFOX regimen) as a potential first-line treatment for
metastatic pancreatic ductal adenocarcinoma (mPDAC). The review is
based on positive results from the pivotal Phase III NAPOLI 3
trial, in which the Onivyde regimen demonstrated a statistically
significant improvement in overall survival (OS) and
progression-free survival (PFS), compared to nab-paclitaxel plus
gemcitabine, with a safety profile consistent with the profiles of
the treatment components. These results were presented at the
January 2023 American Society of Clinical Oncology Gastrointestinal
Cancers Symposium (ASCO GI).
“PDAC is a devastating disease in need of
additional treatment options. The FDA’s decision to accept the sNDA
for this Onivyde-based regimen in treatment-naïve patients with
metastatic disease represents an important milestone in the
potential treatment of this complex form of cancer,” said Howard
Mayer, Executive Vice President and Head of Research and
Development at Ipsen. “We’re committed to developing therapies
which have the potential to make a meaningful difference to the
lives of people living with cancer and look forward to working with
FDA as they review this application.”
The FDA provided a Prescription Drug User Fee
Act goal date of 13 February 2024 for review of Ipsen’s
application. In 2020, the FDA granted Ipsen Fast Track designation
for Onivyde as a first-line combination treatment for mPDAC. The
FDA’s Fast Track program facilitates the development and expedites
the review of medicines that treat serious conditions and have the
potential to address an unmet medical need.
NAPOLI 3 data, as presented
at ASCO GI
2023
- Trial met its primary endpoint of
OS, showing patients in the NALIRIFOX group had a statistically
significant improvement in median OS of 11.1 months, versus 9.2
months in the nab-paclitaxel and gemcitabine group (HR 0.83 [95% CI
0.70–0.99]; p=0.04). At 12 months, the OS rate for the NALIRIFOX
group was 45.6%, and for the nab-paclitaxel and gemcitabine group
it was 39.5%. At 18 months, the OS rate was 26.2% for the NALIRIFOX
group, and 19.3% for the nab-paclitaxel and gemcitabine
group.1
- Trial met its secondary endpoint
showing patients treated with NALIRIFOX had a statistically
significant improvement in median PFS of 7.4 months versus 5.6
months for nab-paclitaxel and gemcitabine (HR 0.69 [95% CI
0.58–0.83]; p=0.0001).1
- The objective response rate was
41.8% (36.8%-46.9%; 95% CI) for patients treated with the NALIRIFOX
regimen versus 36.2% (31.4%-41.2%; 95% CI) for patients treated
with nab-paclitaxel and gemcitabine.1
- The safety profile of NALIRIFOX was
consistent with the profiles of the treatment components. The most
common Grade 3/4 treatment-emergent adverse events with more than
10% frequency in patients receiving NALIRIFOX versus nab-paclitaxel
and gemcitabine included diarrhea (20.3% vs 4.5%), nausea (11.9% vs
2.6%), hypokalemia (15.1% vs 4.0%), anemia (10.5% vs 17.4%) and
neutropenia (14.1% vs 24.5%).1
- ENDS –
About the
NAPOLI 3 trialError! Bookmark not
defined.NAPOLI 3 is a randomized, open-label Phase III trial of an
investigational Onivyde treatment regimen (NALIRIFOX) in patients
who have not previously received chemotherapy for mPDAC. NAPOLI 3
enrolled 770 patients across 205 trial site locations in 18
countries. Patients were randomized to receive Onivyde plus 5
fluorouracil/leucovorin and oxaliplatin (NALIRIFOX regimen; n=383)
twice in a month (days 1 and 15 of 28-day cycle) compared to an
injection of nab-paclitaxel and gemcitabine (n=387) administered
three times a month (days 1, 8, 15 of a 28-day cycle).
About
OnivydeOnivyde is a cancer medicine that blocks an
enzyme called topoisomerase I, which is involved in copying cell
DNA needed to make new cells. By blocking the enzyme, cancer cells
are prevented from multiplying and eventually die. In Onivyde,
irinotecan is enclosed in tiny fat particles called liposomes,
which accumulate in the tumor and release slowly over time.
Onivyde is currently approved in most major
markets including the U.S., the E.U. and Asia in combination with
fluorouracil (5-FU) and leucovorin (LV) for the treatment of
patients with mPDAC after disease progression following
gemcitabine-based therapy. Onivyde is not indicated as a single
agent for the treatment of patients with mPDAC.
Ipsen has exclusive commercialization rights for
the current and potential future indications for Onivyde in the
U.S. Servier, an independent pharmaceutical company with an
international presence in 150 countries, is responsible for the
commercialization of Onivyde outside of the U.S. and Taiwan.
PharmaEngine is a commercial stage oncology company headquartered
in Taipei and is responsible for the commercialization of Onivyde
in Taiwan.
About PDACPDAC
is the most common type of cancer that forms in the pancreas with
approximately 60,000 people diagnosed in the U.S. each year and
nearly 500,000 people globally.2,3 Since there are no specific
symptoms in the early stages, PDAC is often detected late and after
the disease has spread to other parts of the body (metastatic or
stage IV).4 Even in later stages, weight loss, abdominal pain and
jaundice are the most common symptoms making PDAC difficult to
detect.5 Despite significant advances in cancer treatments
since the 1970s, no treatment options for PDAC significantly extend
life.4 Currently, fewer than 20% of people diagnosed with PDAC
survive longer than one year and, overall, pancreatic cancer has
the lowest five-year survival rate of all cancer types globally and
in the U.S.2,3
U.S. IMPORTANT SAFETY
INFORMATION
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.
CONTRAINDICATIONOnivyde is
contraindicated in patients who have experienced a severe
hypersensitivity reaction to Onivyde or irinotecan
hydrochloride.
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 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 including Boxed WARNING for Onivyde.
About Ipsen Ipsen is a
global, mid-sized biopharmaceutical company focused on
transformative medicines in Oncology, Rare Disease and
Neuroscience. With total sales of €3.0bn in FY 2022, Ipsen sells
medicines in over 100 countries. Alongside its external-innovation
strategy, the Company’s research and development efforts are
focused on its innovative and differentiated technological
platforms located in the heart of leading biotechnological and
life-science hubs: Paris-Saclay, France; Oxford, U.K.; Cambridge,
U.S.; Shanghai, China. Ipsen has around 5,400 colleagues worldwide
and is listed in Paris (Euronext: IPN) and in the U.S. through a
Sponsored Level I American Depositary Receipt program (ADR: IPSEY).
For more information, visit ipsen.com
Ipsen’s
forward-looking
statementsThe forward-looking
statements, objectives and targets contained herein are based on
Ipsen’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 Ipsen’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 Ipsen’s expectations regarding future events, including
regulatory filings and determinations. 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 Ipsen.
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
medicine 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. Ipsen must
face or might face competition from generic medicine 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 Ipsen may fail to achieve its
objectives and be forced to abandon its efforts with regards to a
medicine in which it has invested significant sums. Therefore,
Ipsen cannot be certain that favorable results obtained during
preclinical 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 medicine
concerned. There can be no guarantees a medicine will receive the
necessary regulatory approvals or that the medicine 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 healthcare legislation; global trends toward healthcare cost
containment; technological advances, new medicine and patents
attained by competitors; challenges inherent in new-medicine
development, including obtaining regulatory approval; Ipsen’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 Ipsen’s patents and other protections for
innovative medicines; and the exposure to litigation, including
patent litigation, and/or regulatory actions. Ipsen also depends on
third parties to develop and market some of its medicines which
could potentially generate substantial royalties; these partners
could behave in such ways which could cause damage to Ipsen’s
activities and financial results. Ipsen 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
Ipsen’s partners could generate lower revenues than expected. Such
situations could have a negative impact on Ipsen’s business,
financial position or performance. Ipsen 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. Ipsen’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 Ipsen’s Universal Registration Document, available
on ipsen.com
For further information:
Contacts |
|
Investors |
|
Craig
MarksVice President, Investor Relations+44 7584 349 193
|
|
Media |
|
Joanna
ParishGlobal Head of Franchise Communications, Oncology+44
7840 023 741 Elizabeth
Kalina (U.S. media)Vice
President, Communications & Patient Advocacy+1 857 331
0060 |
|
1 Wainberg, Z.A et al. NAPOLI-3: A Randomized, Open-label
Phase 3 Study of Liposomal Irinotecan + 5-fluorouracil/leucovorin +
Oxaliplatin (NALIRIFOX) versus Nab-paclitaxel + Gemcitabine in
Treatment-naïve Patients with Metastatic Pancreatic Ductal
Adenocarcinoma (mPDAC). Presented at ASCO Gastrointestinal Cancers
Symposium, 2023 January 19-21; San Francisco, California.
2 https://seer.cancer.gov/statfacts/html/pancreas.html3
https://www.cancer.net/cancer-types/pancreatic-cancer/statistics4
Orth, M., Metzger, P., Gerum, S. et al. Pancreatic ductal
adenocarcinoma: biological hallmarks, current status, and future
perspectives of combined modality treatment approaches. Radiat
Oncol 14, 141 (2019). https://doi.org/10.1186/s13014-019-1345-65
https://www.cancer.org/cancer/pancreatic-cancer/detection-diagnosis-staging/signs-and-symptoms.html
- Onivyde 1L Filing Acceptance Press Release ENG
Ipsen (EU:IPN)
Graphique Historique de l'Action
De Sept 2024 à Oct 2024
Ipsen (EU:IPN)
Graphique Historique de l'Action
De Oct 2023 à Oct 2024