Ipsen announces European Commission decision on palovarotene for the treatment of FOP

• European Commission determines not to grant marketing authorization approval for palovarotene for fibrodysplasia ossificans progressiva (FOP)
• Decision follows negative opinion by the Committee for Medicinal Products for Human Use, in May
• No currently approved options available in the E.U. for the treatment of FOP, an ultra-rare condition, that continuously and permanently causes abnormal bone formation, leading to progressive mobility loss and shortened life expectancy
• Ipsen to continue seeking regulatory approvals in other countries and regions

PARIS, FRANCE, 19 July 2023 – Ipsen (Euronext: IPN; ADR: IPSEY) announced today that the European Commission has followed guidance provided by the Committee for Medicinal Products for Human Use (CHMP) in May this year, and has not granted marketing authorization for palovarotene, an investigational treatment for fibrodysplasia ossificans progressiva (FOP). Palovarotene is the first treatment to be submitted anywhere in the world for regulatory approval for FOP, an ultra-rare disease with approximately 900 known cases worldwide.

"We worked tirelessly to bring a greatly needed treatment option to patients living with FOP in the E.U.,” said Howard Mayer, Executive Vice President and Head of Research and Development for Ipsen. "We believe that our clinical data provide evidence supporting the effect of palovarotene on the reduction of new, abnormal bone formation, known as heterotopic ossification, which characterizes the disease. We are therefore disappointed that the European Commission decided not to approve this treatment for patients with FOP in Europe. We have learned through this experience, and we have been motivated by the support of the FOP community, including those living with the condition and the doctors and healthcare providers managing their care. This has encouraged us as we continue to progress with other regulatory submissions.”

Palovarotene was studied in a comprehensive clinical program over 15 years. This included MOVE, the first and largest Phase III clinical trial for FOP, a condition that causes abnormal bone growth. The average age of diagnosis for FOP is five years old and the average life expectancy is 56 years old. FOP is a chronic and progressive condition, where flare-ups occur that can lead to the development of new, abnormal bone formulation, accumulating outside of the skeleton in muscles, joints, and other areas of the body. As a result, most people living with FOP eventually lose the ability to eat and drink on their own. By the age of 30 years old, many will need a wheelchair to get around and full-time care. Life expectancy is shortened, as untimely death can be caused by bone formation around the ribcage, leading to breathing problems and cardiorespiratory failure.

"It is devastating to hear that the wait for an innovative treatment for people living with FOP, and their families and caregivers will continue, as this negative decision from the European Commission means that this treatment will not be made available to patients.” said Dr. Genevieve Baujat, Clinical Geneticist Consultant at Necker-Enfants Malades Hospital, Paris, France. "Many of the clinicians that manage patients with this disease in Europe will have participated in the MOVE clinical trial and have seen the potential for palovarotene.”

ENDS

About palovarotene

Palovarotene is an investigational oral medicine that selectively targets the retinoic-acid receptor gamma (RAR?), which is an important regulator of skeletal development and ectopic bone in the retinoid signaling pathway. Palovarotene is designed to mediate the interactions between the receptors, growth factors and proteins within the retinoid signaling pathway to reduce new abnormal bone formation. Palovarotene received Orphan Drug and Breakthrough Therapy Designations from the U.S. Food and Drug Administration (FDA) for the potential treatment of FOP and was granted Priority Review. It remains under FDA review, with a Prescription Drug User Fee Act goal date of 16 August 2023. Palovarotene was also granted orphan medicine designation by the European Medicines Agency (EMA). Palovarotene is in review processes with a number of regulatory authorities including the FDA and the EMA. Palovarotene is currently authorized for use in appropriate patients only in Canada and provisionally in the U.A.E. where it is marketed as Sohonos^TM (palovarotene capsules).

About the MOVE trial
MOVE (NCT03312634) was a Phase III, multicenter, single-arm, open-label trial to assess the efficacy and safety of palovarotene. 107 study participants with FOP received oral palovarotene as a chronic (5mg once daily) and episodic (20mg once daily for 4 weeks, followed by 10mg for =8 weeks for flare-ups and trauma) regimen. The primary endpoint was annualized change in new HO volume measured by low-dose whole-body computed tomography. Efficacy data from participants enrolled in MOVE were compared with data from FOP Natural History Study (NHS) participants untreated beyond standard of care; individuals =65 years of age with clinically diagnosed FOP and a verified ACVR1R206H pathogenic variant were eligible for inclusion in the NHS.

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

For further information:

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 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 latest Universal Registration Document, available on ipsen.com.

Attachment

• Ipsen PR_EC decision Palovarotene_19072023