Ipsen Receives CHMP Negative Opinion for Palovarotene as a Treatment for Fibrodysplasia Ossificans Progressiva in E.U.

Ipsen to request re-examination of CHMP opinion on palovarotene as a potential treatment for fibrodysplasia ossificans progressiva in E.U.

FOP is an ultra-rare disease that continuously and permanently causes abnormal bone formation.1 There are currently no disease-modifying treatment options available in E.U.

Regulatory processes are continuing in other countries including the U.S.

PARIS–(BUSINESS WIRE)–Regulatory News:

Ipsen (Euronext: IPN; ADR: IPSEY) announced today that the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) has recommended not to grant marketing authorization for investigational palovarotene as a treatment for the ultra-rare bone disease, fibrodysplasia ossificans progressiva (FOP). In the E.U. there are currently only symptomatic treatments for FOP, which do not reduce the formation of extra-skeletal bone in patients with the condition. Ipsen will be requesting a re-examination of the CHMP opinion, based on scientific data available from the existing palovarotene clinical trial program.

FOP causes permanent and continuous new bone formation in soft and connective tissues, like muscles, tendons and ligaments, a process known as heterotopic ossification (HO).1 Once formed, it is irreversible.1 The average age of diagnosis is 5 years old2 and ultimately FOP shortens the median life expectancy to 56 years as untimely death is caused by bone formation around the ribcage leading to breathing problems and cardiorespiratory failure.3 FOP has an estimated prevalence of 1.36 per million individuals and about 900 people are diagnosed worldwide; however, the number of confirmed cases varies by country.4,5,6

“We are disappointed with this outcome and will be requesting a re-examination of the CHMP opinion,” said Howard Mayer, Executive Vice President and Head of Research and Development for Ipsen. “We continue to work closely with the EMA to address the outstanding concerns that led to the decision today, with the goal of making this investigational medicine available to appropriate patients, living with this debilitating disease, where no other treatment option exists. Ipsen remains committed to bringing new therapeutic options to the FOP community, which has been instrumental in the development of investigational palovarotene through their involvement in clinical trials. We are enormously grateful for their continued support.”

The CHMP opinion is based on its review of data from MOVE, the first and largest Phase III efficacy and safety trial conducted in FOP. The primary objectives of MOVE were to evaluate the efficacy of palovarotene in reducing new HO volume, as assessed using whole-body computed tomography, compared with patients untreated beyond standard of care from Ipsen’s global FOP natural history study, and to evaluate the safety of investigational palovarotene in adult and pediatric patients with FOP.7,8

“There is a significant need for a treatment specifically developed to help manage the progression of this disease. The data from MOVE have helped us to understand the potential for treatments that reduce HO progression to be used in the management of FOP.” Said Dr. Genevieve Baujat, Clinical Geneticist Consultant at Necker-Enfants Malades Hospital, Paris, France. “Currently, the only therapeutic options available to us are for treating symptoms. We in the FOP community have been waiting a long time for innovations to treat this disabling disease.”

ENDS

About palovarotene

Palovarotene is an investigational oral medicine that selectively targets the retinoic-acid receptor gamma (RARγ), 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 (HO). 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. 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 in Canada and provisionally in the U.A.E. where it is marketed as SohonosTM (palovarotene capsules).9,10

About the MOVE trial

MOVE (NCT03312634) is 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.7

About Ipsen

Ipsen is a global, mid-sized biopharmaceutical company focused on transformative medicines in Oncology, Rare Disease and Neuroscience. With Specialty Care sales of €2.6bn in FY 2021, 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 5,000 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

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1 Kaplan FS et al. The medical management of fibrodysplasia ossificans progressiva: current treatment considerations. Proc Intl Clin Council FOP. 2019;1:1-111.
2 Pignolo RJ et al. The Natural History of Flare-Ups in Fibrodysplasia Ossificans Progressiva (FOP): A Comprehensive Global Assessment. J Bone Miner Res. 2016;31(3):650-656.
3 Kaplan FS, Zasloff MA, Kitterman JA et al. Early mortality and cardiorespiratory failure in patients with fibrodysplasia ossificans progressiva, J Bone Joint Surg Am. 2010;92(3):686-691.
4 Baujat et al. Prevalence of fibrodysplasia ossificans progressiva (FOP) in France: an estimate based on a record linkage of two national databases. Orphanet J Rare Dis. 2017;12:123.
5 IFOPA, What is FOP?, IFOPA. Viewed 30 November 2022. <https://www.ifopa.org/what_is_fop>.
6 Lilijesthrom M, Pignolo RJ, Kaplan FS. Epidemiology of the global fibrodysplasia ossificans progressiva (FOP) community. J Rare Dis Res Treat. 2020;5(2):31-36.
7 Pignolo RJ, Hsiao E, Al Mukaddam M et al. Reduction of New HO in the Open-Label, Phase 3 MOVE Trial of Palovarotene for Fibrodysplasia Ossificans Progressiva (FOP). J Bone Miner Res. 2022.
8 Pignolo RJ, Baujat G, Brown M et al. The natural history of fibrodysplasia ossificans progressiva: A prospective 36-month study. Gen Med. 2022,ISSN 1098-3600,https://doi.org/10.1016/j.gim.2022.08.013.
9 Government of Canada, Notice: Multiple Additions to the Prescription Drug List (PDL). Viewed 30 November 2022, <https://www.canada.ca/en/health-canada/services/drugs-health-products/drug-products/prescription-drug-list/notices-changes/multiple-additions-2022-01-24.html>.
10 Ipsen data on file.

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