Ipsen Announces Withdrawal of Palovarotene NDA, Confirming Intention to Re-submit Following Additional Data Analyses
Disclaimer: Intended for international media and investor audiences only
Ipsen (Euronext: IPN; ADR: IPSEY) today announced, following very recent discussions with the U.S. Food and Drug Administration (FDA), withdrawal of the New Drug Application (NDA) for palovarotene. This follows ongoing dialogue with the FDA following the acceptance of the NDA for Priority Review which was announced on 28 May 2021. During the review and ongoing dialogue between Ipsen and the FDA, it was recognized that additional analyses and evaluation of data collected from Ipsen’s Phase III MOVE and FOP program would be required to progress and complete the review process. It was agreed between Ipsen and the FDA that it would not be possible to complete this within the current NDA review cycle. As a result, Ipsen has therefore confirmed their withdrawal of the NDA for palovarotene. After recent discussion with FDA, Ipsen plans to resubmit to the FDA upon completion of the additional data analyses.
Dr. Howard Mayer, Executive Vice President and Head of Research and Development, Ipsen, said “We remain committed to the FOP community through our clinical programs for Ipsen’s two investigational therapies palovarotene and IPN60130. We recognize the urgency from this community to bring a much-needed treatment option to people living with FOP around the world. Unfortunately, as there is no regulatory mechanism to “pause” the current ongoing review process, we have taken the decision to withdraw the NDA for palovarotene to undertake the additional analyses and evaluation needed, with plans to resubmit the data for palovarotene as soon as possible.”
Palovarotene is an oral, investigational, selective RARγ agonist for the prevention of heterotropic ossification (new bone formation) as a potential treatment for people living with fibrodysplasia ossificans progressiva (FOP). The target regulatory action date assigned by the FDA under a Priority Review status for palovarotene was 30 November 2021.
FOP is an ultra-rare genetic disorder with an estimated prevalence of 1.36 per million individuals globally; however, the number of confirmed cases varies by country.1,2 It is characterized by new bone formation outside of the normal skeletal system, like in soft connective tissues, a process known as heterotopic ossification (HO),3 which can be preceded by painful soft-tissue swelling or “flare-ups”.2 Flare-up episodes are common and are a substantial contributor to the formation of new HO, however HO can form in the absence of a flare-up. HO, once formed, is irreversible and leads to loss of mobility and shortened life expectancy.3
About the palovarotene FOP clinical program
The Phase III MOVE (NCT03312634) trial is an ongoing open-label, single-arm trial evaluating the efficacy and safety of a chronic/flare-up dosing regimen of palovarotene, which comprises a 5mg daily dose that is increased at the start of a flare-up to 20mg for four weeks, followed by 10mg for eight weeks. At the end of the flare-up dosing period, the dose returns to the chronic 5mg daily dose. All dosing is weight-adjusted in skeletally immature participants (those under the age of 18 years with less than 90% skeletal maturity on hand/wrist x-rays performed at screening). The trial is being conducted in Argentina, Australia, Brazil, Canada, France, Italy, Japan, Spain, Sweden, the United Kingdom, and the United States.4 There are two ongoing Phase II (PVO-1A-202 [NCT02279095] and PVO-1A-204 [NCT02979769]) extension trials: 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 trial to evaluate the safety and efficacy of different palovarotene dosing regimens in patients with FOP in France.
In December 2019, a partial clinical hold was applied to participants under the age of 14 years participating in the Phase II (PVO-1A-202/204 and PVO-2A-201) and Phase III (PVO-1A-301) studies at all clinical sites globally. This was due to reports of premature physeal closure (PPC). A decision to pause dosing of palovarotene in all remaining participants 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 January 24, 2020, based on results of a futility analysis as part of the pre-specified interim analysis (Bayesian compound Poisson analysis with square root transformation of the new HO volume data).
*Encouraging therapeutic activity was observed in post hoc analyses of interim data for the Phase III MOVE trial and shared with, and acknowledged by, the Independent Data Monitoring Committee (IDMC). Post hoc analyses included Bayesian compound Poisson analysis without square-root transformation, and weighted linear mixed-effects models (with/without square-root transformation of the new HO volume data). As such, the Company amended the protocol for the Phase III MOVE trial to include updates to the statistical-analysis section, including additional analyses requested by the IDMC, 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 appears to have shifted the statistical conclusion from significant therapeutic benefit to showing futility of the treatment. Dosing for eligible study patients ≥14 years of age has resumed as of March 26, 2020 across the Phase II and Phase III programs for palovarotene in FOP.
Palovarotene is an oral investigational, selective retinoic-acid receptor gamma (RARγ) agonist being developed as a potential treatment for people living with the debilitating ultra-rare genetic disorder fibrodysplasia ossificans progressiva (FOP). Palovarotene, which received rare pediatric disease and breakthrough therapy designations from the FDA for the potential treatment of FOP, was acquired by Ipsen through the acquisition of Clementia Pharmaceuticals in April 2019. The palovarotene NDA was accepted by the U.S. FDA for Priority Review on 28 May 2021.
About fibrodysplasia ossificans progressiva (FOP)
Fibrodysplasia ossificans progressiva (FOP) is an ultra-rare genetic disorder characterized by bone that forms outside the normal skeleton, in muscles, tendons, or soft tissue.3 FOP has an estimated prevalence of 1.36 per million individuals globally; however, the number of confirmed cases varies by country.1,2
Ipsen is a global, mid-sized biopharmaceutical company focused on transformative medicines in Oncology, Rare Disease and Neuroscience; it also has a well-established Consumer Healthcare business. With Total Sales of over €2.5bn in FY 2020, Ipsen sells more than 20 medicines in over 115 countries, with a direct commercial presence in more than 30 countries. 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 c.5,700 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 statements
The 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 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. Ipsen 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 Ipsen 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, Ipsen 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; 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 products; 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 products 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 2020 Registration Document, available on ipsen.com.
1 Lilijesthrom, M & Bogard, B 2016, ‘The global known FOP population’, FOP Drug Development Forum, Boston, MA, 24-25 October.
2 Baujat et al. Prevalence of fibrodysplasia ossificans progressiva (FOP) in France: an estimate based on a record linkage of two national databases. Orphanet Journal of Rare Diseases. 2017; 12:123.
3 Kaplan FS, et al. The medical management of fibrodysplasia ossificans progressiva: current treatment considerations. Proc Intl Clin Council FOP 1:1-111, 2019.
4 ClinicalTrials.gov. An efficacy and safety study of palovarotene for the treatment of fibrodysplasia ossificans progressiva. (MOVE), clinicaltrials.gov, viewed March 2021, <https://clinicaltrials.gov/ct2/show/NCT03312634>.
To view this piece of content from cts.businesswire.com, please give your consent at the top of this page.
Vice President, Investor Relations
+44 7584 349 193
Adrien Dupin de Saint-Cyr
Investor Relations Manager
+33 6 64 26 17 49
Senior Director, Global Communications,
R&D, Business Development and Rare Disease
+44 7557 267 634
Director, US Communications
+001 857 529 1151
About Business Wire
For more than 50 years, Business Wire has been the global leader in press release distribution and regulatory disclosure.
Subscribe to releases from Business Wire
Subscribe to all the latest releases from Business Wire by registering your e-mail address below. You can unsubscribe at any time.
Latest releases from Business Wire
Celltrion’s monoclonal antibody treatment for COVID-19, regdanvimab (CT-P59) becomes the first authorized COVID-19 treatment approved from the Korean Ministry of Food and Drug Safety (MFDS)18.9.2021 16:34:00 EEST | Press release
Celltrion Group announced that the Korean Ministry of Food and Drug Safety (MFDS) approved regdanvimab (CT-P59), a monoclonal antibody treatment for COVID-19 for the extended use in elderly patients aged 50 years and over, or with at least one underlying medical condition (the obese, cardiovascular disease, chronic lung disease, diabetes, chronic kidney disease, chronic liver disease, and patients with immunosuppressive agents) with mild symptoms of COVID-19, and adult patients with moderate symptoms of COVID-19. This marks the first time a monoclonal antibody treatment for COVID-19 has received a full approval to treat patients with COVID-19 from the Korean MFDS. In February, the Korean MFDS granted a Conditional Marketing Authorisation (CMA) for the emergency use of regdanvimab (CT-P59) and allowed the use of CT-P59 in adult patients aged 60 years and over, or with at least one underlying medical condition (cardiovascular, chronic respiratory disease, diabetes, high blood pressure) w
Ipsen: ESMO 2021: Cabometyx® Demonstrates Sustained 78% Reduction in Risk of Disease Progression or Death in People Living With Uncommon Form of Thyroid Cancer18.9.2021 07:30:00 EEST | Press release
Regulatory News: Ipsen (Euronext: IPN; ADR: IPSEY) today announced presentation of new analyses at the European Society for Medical Oncology (ESMO) Congress 2021 across different forms of cancer for people treated with Cabometyx® (cabozantinib). Of note, the final analysis of the pivotal Phase III COSMIC-311 trial (Abstract LBA67) will be presented, with Cabometyx demonstrating a clinically meaningful, sustained efficacy benefit versus placebo in people living with previously treated radioactive iodine-refractory differentiated thyroid cancer (RAI-R DTC). With a median follow-up of 10.1 months, Cabometyx continued to demonstrate superior median progression-free survival (mPFS) with a reduction in the risk of disease progression or death of 78% versus placebo (hazard ratio [HR]: 0.22, 96% confidence interval [CI]: 0.15-0.32; p<0.0001).1 This final analysis is consistent with data from the interim analysis, presented at the American Society of Clinical Oncology (ASCO) Annual Meeting 2021
Unifrax Hosts Groundbreaking Ceremony for SiFAB™ Manufacturing Line17.9.2021 21:46:00 EEST | Press release
Today, Unifrax, a leading manufacturer of high-performance specialty materials, held a ceremonial event celebrating its first large-scale SiFAB™ Silicon Fiber Anode Battery Technology manufacturing line, which is currently under construction at the company’s north central Indiana facility. This press release features multimedia. View the full release here: https://www.businesswire.com/news/home/20210917005495/en/ Unifrax team celebrates SiFAB groundbreaking at New Carlisle plant. (Photo: Business Wire) The event recognized Unifrax’s ongoing partnership with the State of Indiana and St. Joseph County, along with SiFAB’s continued progress. Unifrax executives, along with the SiFAB manufacturing team and local and state government officials, kicked off the ceremony at 10 a.m. EDT at the New Carlisle, IN plant, with remarks by John Dandolph, president and CEO, Unifrax. “Through the support of the State of Indiana and St. Joseph County, we have the ability to leverage our existing New Carli
Prince William announces 15 Finalists for inaugural year of the £50 million Earthshot Prize17.9.2021 20:01:00 EEST | Press release
The Earthshot Prize announces today its first-ever shortlist of 15 Finalists, each with a chance of winning £1million to support their innovative environmental solutions to the greatest challenges facing the planet. Prince William said: "Over half a century ago, President Kennedy’s ‘Moonshot’ programme united millions of people around the goal of reaching the moon. Inspired by this, The Earthshot Prize aims to mobilise collective action around our unique ability to innovate, problem solve and repair our planet. “I am honoured to introduce the 15 innovators, leaders, and visionaries who are the first ever Finalists for The Earthshot Prize. They are working with the urgency required in this decisive decade for life on Earth and will inspire all of us with their optimism in our ability to rise to the greatest challenges in human history.” Launched by Prince William and The Royal Foundation in October 2020, The Earthshot Prize is the most prestigious global environment prize in history. Li
Wipro Announces Co-innovation Space with Google Cloud17.9.2021 16:32:00 EEST | Press release
Wipro Limited (NYSE: WIT, BSE: 507685, NSE: WIPRO), a leading global information technology, consulting and business process services company, today announced the launch of the Wipro-Google Cloud Innovation Arena in Bangalore, India. This cloud collaboration space will provide in-house technical expertise, ensure seamless cloud adoption, and accelerate innovation to drive business transformation for customers. By combining the expertise and resources of Wipro FullStride Cloud Services and Google Cloud, this jointly developed innovation center will offer a unique combination of people, processes, and platforms that will collectively create a futuristic experience for customers globally. This state-of-the-art arena will showcase the talent, tools and best practices required to develop and deploy applications on Google Cloud. Jason Eichenholz, Senior Vice President, Global Head of Ecosystems & Partnerships, Wipro Limited said, “We are excited to strengthen our partnership with Google Clou
Zynga Announces ReVamp, the First Multiplayer Social Deception Game For Snapchat17.9.2021 16:00:00 EEST | Press release
Zynga Inc. (Nasdaq: ZNGA), a global leader in interactive entertainment, announced today that ReVamp, an upcoming multiplayer social deception game, will launch soon in select markets exclusively for Snapchat. The vampire-themed game will be the first social deception title on Snapchat, giving Snapchatters their first chance to sink their teeth into this popular genre. This press release features multimedia. View the full release here: https://www.businesswire.com/news/home/20210917005012/en/ Zynga Announces ReVamp, the First Multiplayer Social Deception Game For Snapchat (Graphic: Business Wire) ReVamp is a real-time multiplayer imposter game where players aim to reveal who the vampire player is among their group of friends while they renovate the rooms of an old mansion. In the game, human players must complete renovation tasks, such as demolition and building, to improve their chances of survival while identifying and defeating the vampire during the voting phase. Vampire players mu
BeiGene Receives Positive CHMP Opinion for BRUKINSA® (Zanubrutinib) for the Treatment of Adults with Waldenström’s Macroglobulinemia17.9.2021 15:00:00 EEST | Press release
BeiGene (NASDAQ: BGNE; HKEX: 06160) today announced the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) has adopted a positive opinion, recommending approval of BRUKINSA (zanubrutinib) for the treatment of adult patients with Waldenström’s macroglobulinemia (WM) who have received at least one prior therapy or first-line treatment for patients unsuitable for chemo-immunotherapy. “Bruton’s tyrosine kinase (BTK) inhibitors have emerged as a promising treatment for WM, yet treatment discontinuation due to lack of response or side effects remains a concern,” said Prof. Christian Buske, Medical Director at the University Hospital Ulm, Germany, and a trial investigator of the ASPEN study. “The ASPEN trial demonstrated that BRUKINSA provided deep and durable responses and offered substantial improvements in safety and tolerability over standard therapy. Patients in Europe with WM may soon have a new treatment option that can offer improved outcomes.
In our pressroom you can read all our latest releases, find our press contacts, images, documents and other relevant information about us.Visit our pressroom