{"id":26401,"date":"2022-09-28T09:00:00","date_gmt":"2022-09-28T07:00:00","guid":{"rendered":"https:\/\/d36deud6t4mnhi.cloudfront.net\/press-releases\/ipsens-global-natural-history-study-of-fibrodysplasia-ossificans-progressiva-shows-debilitating-impact-of-the-disease-over-an-individuals-lifetime\/"},"modified":"2024-07-22T12:06:13","modified_gmt":"2024-07-22T10:06:13","slug":"ipsens-global-natural-history-study-of-fibrodysplasia-ossificans-progressiva-shows-debilitating-impact-of-the-disease-over-an-individuals-lifetime","status":"publish","type":"press_release","link":"https:\/\/www.ipsen.com\/press-releases\/ipsens-global-natural-history-study-of-fibrodysplasia-ossificans-progressiva-shows-debilitating-impact-of-the-disease-over-an-individuals-lifetime\/","title":{"rendered":"Ipsen\u2019s global Natural History Study of Fibrodysplasia Ossificans Progressiva shows debilitating impact of the disease over an individual\u2019s lifetime"},"content":{"rendered":"\n

First prospective study to assess the association of fibrodysplasia ossificans progressive (FOP) flare-ups and extra-skeletal bone growth (heterotopic ossification or HO) with functional impairment<\/em><\/p>\n\n\n\n

PARIS, France, 28 September 2022 \u2013 <\/strong>Ipsen (Euronext: IPN; ADR: IPSEY) today announced the publication of its Natural History Study (NHS) of FOP in Genetics in Medicine, <\/em>the official journal of the American College of Medical Genetics and Genomics (ACMG)<\/em>. This is the first time a global, prospective, longitudinal evaluation of FOP has been carried out, with data collected over a period of 36 months. Findings demonstrated the debilitating impact and progressive nature of the disease, with the greatest progression of new heterotopic ossification (HO; or bone growth that takes place outside of the normal skeletal system in joints and soft connective tissues), occurring during childhood and early adulthood.1<\/sup><\/p>\n\n\n\n

\u201cNatural history studies are essential to understanding ultra-rare diseases with high unmet need like FOP, increasing our knowledge around the natural course of disease, diagnoses, monitoring techniques, potential biomarkers and new outcome measures,\u201d said Dr. Robert Pignolo, Professor of Geriatric Medicine, Mayo Clinic, USA. \u201cThis is the first study of its kind following the progression of FOP over three years. These results demonstrate the significant impact of the disease on people living with FOP. Furthermore, it will facilitate the evaluation of meaningful endpoints in the development of new therapies, which are critically needed for individuals with FOP.\u201d<\/p>\n\n\n\n

Results from the NHS demonstrated at month 36, across the whole study population, a mean of 2.6 body regions with new HO; this was highest (3.9) in those aged between two and eight years and lowest (1.5) in those aged 25 \u2013 65 years. However, although individuals aged 25 \u2013 65 years had the lowest new HO volume at annual visits, approximately 70% continued to accumulate new HO across the duration of the study. These data confirmed the progressive nature of FOP with characteristic patterns of growth, starting in younger individuals initially across the upper and mid-torso, progressing into hip and lower-leg regions, and with accumulation of HO occurring over time and following disease flare-ups.1<\/sup><\/p>\n\n\n\n

The assessment of flare-ups showed, 82 (71.9%) individuals experienced a total of 229 flare-ups, most commonly in the upper back (17.9%), hip (14.8%) and shoulder (10.9%). Individuals between the ages of two and eight years, were most likely to report more than one flare-up throughout the study duration. For those who experienced flare-ups, the most common symptoms were pain and soft tissue swelling. Imaging at the site of the flare-up revealed HO occurring at the time of the flare-up, with many individuals going on to experience new HO in the following 12 weeks.1<\/sup><\/p>\n\n\n\n

In addition, the study assessed functional impairment, changes in joint function in association with HO, need for aids, assistive devices and adaptations (AADA), and medical events. Across the population studied, total HO volume and new AADAs increased during the study, with more than 9 in every 10 individuals using at least one new AADA during the study, suggesting the use of AADA could be a real-world indicator of decreased mobility in FOP. In comparison, there were only limited changes in functional and patient-reported outcomes, possibly due to the study duration being too short to detect substantial changes in joint function.1<\/sup> The WBCT data from the NHS confirmed new annualized HO volume as a clinically meaningful endpoint that can be used in interventional clinical trials.1<\/sup>  <\/strong><\/p>\n\n\n\n

\u201cAs an ultra-rare disease there is still a lot we have to understand about the nature and progression of FOP, said Dr Howard Mayer, Head of Research and Development, Ipsen. \u201cThis first prospective study carried out over a 3-year period, has helped to advance our knowledge of important characteristics of the disease, including when in a persons\u2019 lifetime new HO is most likely to form and how it progresses over time, in addition to better understanding the relationship between use of AADA and mobility. We are grateful to the significant number of individuals with FOP who participated in this important study.\u201d<\/p>\n\n\n\n

FOP is an ultra-rare genetic disorder with an estimated prevalence of 1.36 per million individuals2<\/sup>. The median age at time of FOP diagnosis is five years old.3<\/sup> It is characterized by HO,4<\/sup> which can be preceded by painful soft-tissue swellings or \u2019flare-ups\u2019.3<\/sup> Flare-up episodes are a substantial contributor to the formation of new HO, which once formed is irreversible.4<\/sup> Disability is therefore cumulative and most patients need to use a wheelchair by their 20\u2019s and require assistance to perform activities of daily living.5,6<\/sup> This loss of mobility, in addition to numerous life-limiting complications of FOP, leads to markedly shortened life expectancy.7<\/sup><\/p>\n\n\n\n

Previous Natural History Studies in FOP have used retrospective3,7,8,9,10,11 <\/sup>or patient-reported12,13 <\/sup>data to provide insights into disease characteristics and changes in joint mobility. In this prospective NHS, HO progression was evaluated using whole-body computed tomography (WBCT) scans at baseline and months 12, 24, and 36. Flare-ups were assessed using computed tomography (CT) scans or X-rays on the day the individual presented with the flare-up and at week 12, to evaluate the extent of HO at the flare-up site.1<\/sup><\/p>\n\n\n\n

It is estimated that 15% of all known individuals with FOP were included in the NHS at the time of the study.2<\/sup> Given the size of the dataset relative to the known world-wide population of people with FOP, this represents the largest, international, most comprehensive, prospective natural history study of FOP to date.1<\/sup><\/p>\n\n\n\n

About the FOP Natural History Study<\/strong><\/p>\n\n\n\n

The study was conducted across eight international sites. Median age was 15 years and there were more males than females. Median time since the last flare-up prior to enrollment was 0.5 years. Two thirds of participants (66.7%) reported having \u22651 flare-up, with an overall mean of 2.5 flare-ups per individual, in the 12 months prior to enrollment. All participants had great toe malformations, and approximately half had thumb malformations. Overall, 114 individuals 4 to 56 years old participated in the study; of these, 33 individuals completed the study. All participants were genetically diagnosed with FOP carrying the activin receptor type-1 (ACVR1)<\/em>R<\/sup>206H<\/sup> pathogenic variant, the five most common clinical signs present at baseline were restricted chest expansion, hearing loss (sensorineural and\/or conductive), locked jaw, fractures and reduced vital capacity. Over 36 months, new-onset medical history was reported across all categories; the musculoskeletal and cardiopulmonary systems were most affected.1<\/sup><\/p>\n\n\n\n

\nhttps:\/\/www.gimjournal.org\/article\/S1098-3600(22)00904-2\/fulltext\n<\/div><\/figure>\n\n\n\n

About Ipsen<\/strong><\/p>\n\n\n\n

Ipsen is a global, mid-sized biopharmaceutical company focused on transformative medicines in Oncology, Rare Disease and Neuroscience. With Specialty Care sales of \u20ac2.6bn in 2021, Ipsen sells medicines in over 100 countries (35 with a direct presence). Alongside its external-innovation strategy, the Company\u2019s 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<\/strong><\/a><\/p>\n\n\n\n

Ipsen\u2019s forward looking statements<\/strong><\/p>\n\n\n\n

The forward-looking statements, objectives and targets contained herein are based on Ipsen\u2019s 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\u2019s future ability to achieve its financial targets, which were set assuming reasonable macroeconomic conditions based on the information available today. Use of the words \u2018believes\u2019, \u2018anticipates\u2019 and \u2018expects\u2019 and similar expressions are intended to identify forward-looking statements, including Ipsen\u2019s 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\u2019s 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\u2019s 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\u2019s 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\u2019s partners could generate lower revenues than expected. Such situations could have a negative impact on Ipsen\u2019s 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\u2019s business is subject to the risk factors outlined in its registration documents filed with the French Autorit\u00e9 des March\u00e9s Financiers. The risks and uncertainties set out are not exhaustive and the reader is advised to refer to Ipsen\u2019s 2021 Universal Registration Document, available on <\/strong>ipsen.com<\/strong><\/a>.<\/strong><\/p>\n\n\n\n

For further information:<\/u><\/strong><\/p>\n\n\n\n

Investors<\/u><\/strong><\/td> <\/td><\/tr>
Craig Marks<\/strong>
Vice President, Investor Relations
+44 7584 349 193<\/td>		Adrien Dupin de Saint-Cyr<\/strong>
Investor Relations Manager
+33 6 64 26 17 49<\/td><\/tr>
Media<\/u><\/strong><\/td> <\/td><\/tr>
Anna Gibbins<\/strong>\n

 <\/p>\n

Global Head Franchise Communications, Rare Diseases
+44 7717 801900<\/p>\n<\/td>

 <\/td><\/tr>
 <\/td> <\/td><\/tr><\/tbody><\/table><\/figure>\n\n\n\n
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  1. Pignolo RJ, Baujat G, Brown M, et al. The natural history of fibrodysplasia ossificans progressiva: A prospective 36-month study. Genetics in Medicine<\/em> 2022,ISSN 1098-3600,https:\/\/doi.org\/10.1016\/j.gim.2022.08.013.<\/li>\n\n\n\n
  2. Liljesthr\u00f6m M, Pignolo R, Kaplan F. Epidemiology of the global fibrodysplasia ossificans progressiva (FOP) community. J Rare Dis Res Treat. <\/em>2020;5(2):31\u201336.<\/li>\n\n\n\n
  3. Pignolo RJ et al. The Natural History of Flare-Ups in Fibrodysplasia Ossificans Progressiva (FOP): A Comprehensive Global Assessment. J Bone Miner Res<\/em>. 2016;31(3):650-656.<\/li>\n\n\n\n
  4. Kaplan, FS, et al. The medical management of fibrodysplasia ossificans progressiva: current treatment considerations. Proc Intl Clin Council FOP.<\/em> 2019; 1:1-111.<\/li>\n\n\n\n
  5. Pignolo RJ, Shore EM, Kaplan FS. Fibrodysplasia ossificans progressiva: diagnosis, management, and therapeutic horizons. Pediatr Endocrinol Rev.<\/em> 2013;10 Suppl 2:437-448.<\/li>\n\n\n\n
  6. Ortiz-Agapito F, Colmenares-Bonilla D. Quality of life of patients with fibrodysplasia ossificans progressiva. J Child Orthop. <\/em>2015;9(6):489-493.<\/li>\n\n\n\n
  7. Kaplan FS, Zasloff MA, Kitterman JA, et al. Early mortality and cardiorespiratory failure in patients with fibrodysplasia ossificans progressiva. J Bone Joint Surg Am.<\/em> 2010;92(3):686-691.<\/li>\n\n\n\n
  8. Connor JM, Evans DA. Fibrodysplasia ossificans progressiva. The clinical features and natural history of 34 patients. J Bone Joint Surg Br.<\/em> 1982;64(1):76-83.<\/li>\n\n\n\n
  9. Morales-Piga A, Bachiller-Corral J, Trujillo-Tiebas MJ, et al. Fibrodysplasia ossificans progressiva in Spain: epidemiological, clinical, and genetic aspects. Bone<\/em>. 2012;51(4):748-755.<\/li>\n\n\n\n
  10. Smith R, Athanasou NA, Vipond SE. Fibrodysplasia (myositis) ossificans progressiva: clinicopathological features and natural history. QJM<\/em>. 1996;89(6):445-446.<\/li>\n\n\n\n
  11. Zhang W, Zhang K, Song L, et al. The phenotype and genotype of fibrodysplasia ossificans progressiva in China: a report of 72 cases. Bone<\/em>. 2013;57(2):386-391.<\/li>\n\n\n\n
  12. Cohen RB, Hahn GV, Tabas JA, et al. The natural history of heterotopic ossification in patients who have fibrodysplasia ossificans progressiva. A study of forty-four patients. J Bone Joint Surg Am.<\/em> 1993;75(2):215-219.<\/li>\n\n\n\n
  13. Kaplan FS, Al Mukaddam M, Pignolo RJ. Longitudinal patient-reported mobility assessment in fibrodysplasia ossificans progressiva (FOP). Bone<\/em>. 2018;109:158-161.<\/li>\n<\/ol>\n\n\n\n

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