Ipsen to reinitiate palovarotene dosing in
patients 14 years of age and older with fibrodysplasia ossificans
progressiva
Ipsen to terminate MO-Ped trial (PVO-2A-201)
in patients with multiple osteochondromas to analyze accumulated
data and assess the future of palovarotene in this
indication
Regulatory News:
Ipsen (Euronext: IPN; ADR: IPSEY) announced today it will begin
to reinitiate palovarotene dosing in patients 14 years of age and
older currently participating in its fibrodysplasia ossificans
progressiva (FOP) clinical program. The Food and Drug
Administration (FDA) in the U.S. has confirmed they have no safety
concerns with restarting dosing in patients 14 years of age and
older. Clearance to reinitiate dosing in these patients has also
been received to date from the Medicines and Healthcare Products
Regulatory Agency (MHRA) in the UK, the National Agency for the
Safety of Medicines and Health Products Safety (ANSM) in France,
the Medical Products Agency (MPA) in Sweden, the Italian Medicines
Agency (AIFA), the National Administration of Drugs, Foods, and
Medical Devices (ANMAT) in Argentina, the Spanish Agency of
Medicines and Medical Devices (AEMPS), and Health Canada (HC).
The decision to pause dosing of palovarotene in the global Phase
III MOVE trial (PVO-1A-301), as well as the ongoing Phase II
(PVO-1A-202/204) extension studies in FOP was made by Ipsen on 24
January 2020, based on results of a futility analysis as part of
the pre-specified interim analysis.
Encouraging therapeutic activity was observed in preliminary
post-hoc analyses of interim data for the Phase III MOVE trial and
shared with, and acknowledged by, the Independent Data Monitoring
Committee (IDMC). As such, the company amended the protocol for the
Phase III MOVE trial to include updates to the statistical analysis
section as recommended by the IDMC to allow for additional analyses
to be performed in addition to the primary pre-specified analysis.
The protocol amendments are based on the IDMC’s observation that
the protocol pre-specified statistical model may have negatively
affected the efficacy analysis and shifted the statistical
conclusion from significant therapeutic benefit to showing futility
of the treatment.
“We are pleased that Ipsen has received the approval to
reinitiate dosing in patients 14 years of age and older in the
Phase III MOVE trial from several regulatory agencies to date
following review of the additional data. After consultation with
patient groups and investigators, we have been working diligently
with all relevant stakeholders to restart the trial as quickly as
possible,” said Dr. Howard Mayer, Executive Vice President and Head
of Research and Development at Ipsen. “We remain committed to
bringing palovarotene to patients living with this devastating
disease and will continue our conversations with the health
authorities to determine the most appropriate regulatory path
forward.”
Ipsen is now working to obtain the approvals from the ethics
committee (EC) of each clinical site and, upon receipt of both
regulatory approval where required and EC approval, the
reinitiation of dosing may begin. At this point, physicians or
trial coordinators will contact eligible patients to share more
details and advise on appropriate steps for the reinitiation of
treatment. Appropriate measures will also be taken to ensure the
safety of FOP patients who restart dosing in light of the ongoing
COVID-19 pandemic, taking into consideration local regulatory and
health authority guidance, as well as the ability of individual
investigators and sites to adequately monitor patient safety.
The FDA partial clinical hold issued on 4 December 2019 for the
pediatric population under the age of 14 for FOP and multiple
osteochondroma (MO) studies remains in effect. In relation to this,
Ipsen is currently addressing the questions from the FDA and other
health authorities to expeditiously establish a course of action
for FOP studies for the pediatric population under the age of
14.
Ipsen is also addressing the partial clinical hold questions
from the FDA related to the MO program. However, Ipsen has taken
the decision to terminate its MO-Ped trial (PVO-2A-201) conducted
under IND135403 to analyze the accumulated data to better inform on
the efficacy, safety and future of palovarotene in MO, and to
potentially establish a path forward for palovarotene in this
indication, including an assessment as to the potential for an NDA
submission to the FDA. Ipsen believes however that an NDA
submission for the treatment of MO based on the MO-Ped trial
(PVO-2A-201) conducted under IND135403 is highly unlikely. The
reasons for Ipsen’s decision include the time that the partial
clinical hold has been in place leading to a significant gap in
dosing which may compromise the integrity of the data, that the
trial was not fully enrolled at the time the partial clinical hold
was instituted (as such, very few patients had reached the trial
midpoint), and there is no efficacy data available in this patient
population currently to further inform a benefit/risk
assessment.
About the FOP clinical program The Phase III MOVE
(PVO-1A-301) trial is an open-label, single-arm, efficacy and
safety trial evaluating a chronic/episodic dosing regimen of
palovarotene which includes a 5 mg daily dose of palovarotene in
addition to the episodic 20/10 mg dosing regimen following any
flare-ups (note that doses are weight-adjusted). The trial is being
conducted in the U.S., Argentina, Australia, Brazil, Canada,
France, Italy, Japan, Spain, Sweden and the United Kingdom. There
are two ongoing Phase II (PVO-1A-202/204) extension studies; 1)
Study 202 an open-label extension of Study 201, the initial Phase
II randomized, double-blind, multi-center trial, and 2) Study 204
an open-label study corresponding to PVO-1A-202 to evaluate the
safety and efficacy of different palovarotene dosing regimens in
subjects with FOP in France.
About palovarotene Palovarotene is a RARγ agonist being
developed as a potential treatment for patients with ultra-rare and
debilitating bone diseases, including fibrodysplasia ossificans
progressiva (FOP) and multiple osteochondromas (MO), as well as
other conditions including dry eye disease. Palovarotene, which had
rare pediatric disease and breakthrough therapy designations for
the treatment of an ultra-rare bone disorder, was acquired by Ipsen
through the acquisition in April 2019 of Clementia
Pharmaceuticals.
About fibrodysplasia ossificans progressiva (FOP)
Fibrodysplasia ossificans progressiva (FOP) is an ultra-rare,
severely disabling disorder characterized by bone that forms
outside the normal skeleton, in muscles, tendons or soft tissue.1
FOP is among the rarest of human diseases, and while there are
approximately 1,000 confirmed cases globally, the prevalence of FOP
is estimated at approximately 1.36 per million individuals.2,3
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 €2.5 billion in 2019, 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 5,800
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.
Ipsen—Cautionary Note Regarding Forward-Looking
Statements 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. 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 and also taking into
consideration assessment delays of certain clinical trials in light
of the ongoing COVID-19 pandemic. 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
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The Group also depends on third parties to develop and market some
of its products which could potentially generate substantial
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Group cannot be certain that its partners will fulfil their
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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).
References
- The Medical Management of Fibrodysplasia Ossificans
Progressiva: Current Treatment Considerations, IFOPA. Accessed:
March 2020. Available:
http://fundacionfop.org.ar/wp-content/uploads/2019/05/GUIDELINES-May-2019.pdf
- Lilijesthrom M & Bogard B. FOP Drug Development Forum.
Boston, MA; 2016.
- Baujat et al. Orphanet Journal of Rare Diseases (2017)
12:123.
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version on businesswire.com: https://www.businesswire.com/news/home/20200325005667/en/
Media Christian Marcoux, M.Sc. Senior Vice President,
Global Communications +33 (0)1 58 33 67 94
christian.marcoux@ipsen.com
Fanny Allaire Senior Director, France Hub, Global Communications
+33 (0) 1 58 33 58 96 fanny.allaire@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
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