Pierre Fabre and the EspeRare Foundation start the EDELIFE clinical trial of a prenatal treatment for a rare genetic disease, XLHED
15 November 2021
Geneva, Switzerland, Castres, France (November 15, 2021) – The EspeRare Foundation and the Pierre Fabre group announced today the start of the EDELIFE clinical trial aimed at confirming the safety and efficacy of ER004, a prenatal treatment for XLHED (X-linked Hypohidrotic Ectodermal Dysplasia), a rare and debilitating congenital disease. If positive, the study could lead to the first approved treatment for XLHED by 2026.
XLHED is a rare disease which affects approximately 4/100,000 live male births every year. This genetic disorder is a dermatologic-related condition which leads to abnormal development of the skin, sweat glands, sebaceous glands, hair, oral cavity and respiratory mucosal glands resulting in serious clinical manifestations such as hyperthermia, craniofacial anomalies and recurrent respiratory infections.
Starting patient enrolment in the EDELIFE clinical trial is a huge milestone for the Hypohidrotic Ectodermal Dysplasia community. Administered during the second and third trimesters of pregnancy, ER004 has the potential to become a ‘single-course treatment’, which significantly improves the symptoms of this debilitating disease throughout the lives of patients. If successful, ER004 could fundamentally change the lives of these patients and may also pave the way for other prenatal therapies to correct genetic diseases before birth.
The EDELIFE clinical trial will investigate the efficacy and safety of intra-amniotic ER004 as a prenatal treatment for male foetuses who have been confirmed to have XLHED. In the main study phase, efficacy and safety of approximately 15 treated children will be assessed up to 6 months of age and safety of the mothers will be assessed up to 1 month after delivery. In the long-term follow-up phase, efficacy and safety of the treated children will be assessed up to 5 years of age. Treated children’s sweating ability will be compared to that of an untreated affected relative, when available, or to that of a genotype-matched control subject coming from disease natural history data. The main phase of the clinical study is expected to last until 2025.
The study starts first in Germany, at the University Hospital of Erlangen, with Pr Schneider as the study coordinating investigator. Additional study centers will be progressively opened in France, Italy, Spain, United Kingdom and the USA.
The EDELIFE study truly exemplifies Pierre Fabre’s commitment to supporting those with rare dermatologic diseases as we have already done in infantile hemangiomas; Our priority is to enrol 20 pregnant women with a confirmed diagnosis of XLHED in the foetus. As this is a very rare condition, together with the patient community, we are doing everything we can to support these women participate in the study, including helping them travel to a nearby country if there is no open investigational site in their own country.
The treatment ER004 has received the “breakthrough therapy” designation in 2020 by the US Federal Drug Administration (FDA). Its clinical development also benefits from the European Medical Agency’s (EMA) PRIME (PRIority MEdicines) program.
A dedicated web site (www.EDELIFEclinicaltrial.com) is being made available for interested families, providing details on the clinical trial and the conditions for enrolment. Details are also available on www.clinicaltrial.gov.
XLHED is a severe genetic disorder that affects the structure of the ectoderm, the most exterior part of the three primary germ layers formed during early embryonic life, from which the skin and its appendages are derived. XLHED is caused by mutations in EDA, a gene that encodes an important developmental signaling protein, EDA1. The absence of functional EDA1 in the ectoderm results in abnormal development of the skin, sweat glands, sebaceous glands, hair, oral cavity, and respiratory mucosal glands.
ER004 is a pioneering in-utero therapy designed to replace the function of endogenous Ectodysplasin A1 (EDA1), a protein key to the normal development of ectodermal structures in the foetus. ER-004 is a recombinant, soluble, and humanized form of EDA1 that is given as a single course treatment and delivered through intra-amniotic injections during the late stage of pregnancy. This approach has already demonstrated a significant potential in humans where it normalized sweat gland function in three patients treated in this fashion by Prof. Holm Schneider at the University Hospital Erlangen in Germany. First results were published in the New England Journal of Medicine1 and in the British Journal of Clinical Pharmacology2 as well as featured in Nature Medicine's Research Highlights3.
About the EspeRare foundation
EspeRare is a Swiss non-profit organization founded in 2013 that is committed to improve the lives of children with life-threatening rare diseases. EspeRare addresses the unmet medical needs of these children by uncovering the potential of existing treatments. EspeRare's innovative model combines pharmaceutical know-how with philanthropic, public and private investments to develop and bring to life these discontinued therapies. With its unique patient-centred approach to drug development, EspeRare engages the patient community at each step of the process, with the intent of giving children and their families fair access to these therapies and a new hope for the future.
For more information, please visit www.esperare.org
About Pierre Fabre
Pierre Fabre is the 2nd largest dermo-cosmetics laboratory in the world, the 2nd largest private French pharmaceutical group and the market leader in France for products sold over the counter in pharmacies. Its portfolio ranges across several medical franchises and international brands, including Pierre Fabre Oncology, Pierre Fabre Dermatology, Eau Thermale Avène, Klorane, Ducray, René Furterer, A-Derma, Naturactive and Pierre Fabre Oral Care.
In 2020, Pierre Fabre generated €2.3 billion in revenues, 65% of which came from international sales. Established in the Occitanie region since its creation, and manufacturing over 95% of its products in France, the Group employs some 10,000 people worldwide. Its products are distributed in about 130 countries.
Pierre Fabre is 86%-owned by the Pierre Fabre Foundation, a government-recognised public-interest foundation, and secondarily by its own employees through an international employee stock ownership plan.
In 2020, Ecocert Environment assessed the Group’s corporate social and environmental responsibility approach in accordance with the ISO 26000 sustainable development standard for the 2nd consecutive year and confirmed its “Excellence” level.
1. Prenatal Correction of X-Linked Hypohidrotic Ectodermal Dysplasia. Schneider H, Faschingbauer F, Schuepbach-Mallepell S, Körber I, Wohlfart S, Dick A, Wahlbuhl M, Kowalczyk-Quintas C, Vigolo M, Kirby N, Tannert C, Rompel O, Rascher W, Beckmann MW, Schneider P. N Engl J Med 2018; 378: 1604-1610
2. Safety and immunogenicity of Fc-EDA, a recombinant ectodysplasin A1 replacement protein, in human subjects. Körber I, Klein OD, Morhart P, Faschingbauer F, Grange DK, Clarke A, Bodemer C, Maitz S, Huttner K, Kirby N, Durand C, Schneider H. Br J Clin Pharmacol. 2020;86(10):2063-2069
3. In utero correction of a genetic disorder. Stower H. Nature Medicine 2018; 24: 702