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4 March 2015 EMA/COMP/662962/2010 Rev.1 Committee for Orphan Medicinal Products Lentiviral vector carrying the Fanconi anaemia-a (FANCA) gene for the treatment of Fanconi anaemia type A First publication 18 January 2011 Rev.1: sponsor s name and address change 4 March 2015 Disclaimer Please note that revisions to the Public Summary of Opinion are purely administrative updates. Therefore, the scientific content of the document reflects the outcome of the Committee for Orphan Medicinal Products (COMP) at the time of designation and is not updated after first publication. On 17 December 2010, orphan designation (EU/3/10/822) was granted by the European Commission to the Centre for Biomedical Network Research on Rare Diseases (CIBERER), Spain, for lentiviral vector carrying the Fanconi anaemia-a (FANCA) gene for the treatment of Fanconi anaemia type A. In July 2014, Centre for Biomedical Network Research on Rare Diseases (CIBERER) changed name to Centro de Investigación Biomédica en Red (CIBER). What is Fanconi anaemia type A? Fanconi anaemia is an inherited genetic disorder. Type A is the most common form of Fanconi anaemia. Patients with Fanconi anaemia type A have a defect in the Fanconi-A (FANCA) gene normally involved in the recognition and repair of damaged cell DNA. The defect prevents cells from replicating normally. Patients with Fanconi anaemia are generally born with physical malformations, and over the years, they develop a wide range of complications such as bone marrow failure (the body s inability to produce new blood cells) and cancers such as acute myeloid leukaemia (a cancer of the white blood cells). Bone marrow failure normally occurs during childhood. Fanconi anaemia is a severely debilitating and life-threatening condition because of the bone marrow failure which leads to shortened life expectancy. 30 Churchill Place Canary Wharf London E14 5EU United Kingdom Telephone +44 (0)20 3660 6000 Facsimile +44 (0)20 3660 5555 Send a question via our website www.ema.europa.eu/contact An agency of the European Union European Medicines Agency, 2015. Reproduction is authorised provided the source is acknowledged.

What is the estimated number of patients affected by the condition? At the time of designation, Fanconi anaemia type A affected between 0.01 and 0.05 in 10,000 people in the European Union (EU). This was equivalent to a total of between 500 and 2,500 people *, and is below the ceiling for orphan designation, which is 5 people in 10,000. This is based on the information provided by the sponsor and the knowledge of the Committee for Orphan Medicinal Products (COMP). What treatments are available? At the time of designation, while different medicines were authorised to treat specific complications resulting from the disease, there were no satisfactory treatments authorised in the EU for Fanconi anaemia. The only treatment available was allogeneic haematopoietic (blood) stem cell transplantation (a complex procedure where the patient receives stem cells from a matched donor to help restore the bone marrow), but the availability of suitable donors was limited. How is this medicine expected to work? Lentiviral vector carrying the FANCA gene is a gene therapy product. This is a medicine that works by delivering genes into the body. The medicine is made up of a virus that contains normal copies of the FANCA gene. Haematopoietic stem cells (cells that can develop into different types of blood cells) are first taken from the patient and then infected with the virus so that the healthy FANCA gene is carried into the cells. These modified cells are transplanted back into the patient where they are expected to start producing healthy blood cells thus altering or halting the disease. The type of virus used in this medicine (lentivirus) is modified so that it does not cause disease in humans. What is the stage of development of this medicine? The effects of lentiviral vector carrying the FANCA gene have been evaluated in experimental models. At the time of submission of the application for orphan designation, no clinical trials with the medicine had been started. At the time of submission, the medicine was not authorised anywhere in the EU for Fanconi anaemia type A or designated as an orphan medicinal product elsewhere for this condition. In accordance with Regulation (EC) No 141/2000 of 16 December 1999, the COMP adopted a positive opinion on 7 October 2010 recommending the granting of this designation. Opinions on orphan medicinal product designations are based on the following three criteria: the seriousness of the condition; the existence of alternative methods of diagnosis, prevention or treatment; either the rarity of the condition (affecting not more than 5 in 10,000 people in the EU) or insufficient returns on investment. * Disclaimer: For the purpose of the designation, the number of patients affected by the condition is estimated and assessed on the basis of data from the European Union (EU 27), Norway, Iceland and Liechtenstein. At the time of designation, this represented a population of 506,300,000 (Eurostat 2010). EMA/COMP/662962/2010 Page 2/5

Designated orphan medicinal products are products that are still under investigation and are considered for orphan designation on the basis of potential activity. An orphan designation is not a marketing authorisation. As a consequence, demonstration of quality, safety and efficacy is necessary before a product can be granted a marketing authorisation. For more information Sponsor s contact details: Centro de Investigación Biomédica en Red (CIBER) Instituto de Salud Carlos III Pabellón 11, Planta 0 C/ Monforte de Lemos 3-5 28029 Madrid Spain Tel. +34 918 22 25 79 Fax +34 915 57 08 12 E-mail: gestores@ciber.es For contact details of patients organisations whose activities are targeted at rare diseases see: Orphanet, a database containing information on rare diseases which includes a directory of patients organisations registered in Europe. European Organisation for Rare Diseases (EURORDIS), a non-governmental alliance of patient organisations and individuals active in the field of rare diseases. EMA/COMP/662962/2010 Page 3/5

Translations of the active ingredient and indication in all official EU languages 1, Norwegian and Icelandic Language Active ingredient Indication English Bulgarian Czech Danish Dutch Estonian Finnish French German Greek Hungarian Italian Latvian Lithuanian Maltese Polish Portuguese Romanian Slovak Slovenian Spanish Lentiviral vector carrying the Fanconi anaemia-a (FANCA) gene Лентивирусен вектор, носещ ген на анемията на Фанкони A (FANCA) Lentivirový nosič přenášející Fanconiho anémii A (FANCA) gen Lentivirus-vektor bærende Fanconis anæmi A (FANCA) genet Lentivirale vector dewelke het Fanconianemie A (FANCA) gen draagt Lentiviraalne vektor, mis sisaldab Fanconi aneemia A (FANCA) geeni Fanconin anemian A (FANCA) -geenin sisältävä lentivirusvektori Vector lentiviral portant le gène de l anémie de Fanconi A (FANCA) Lentiviraler Vektor der das Fanconi-Anämie A (FANCA) Gen beinhaltet Λεντι-ιικοί φορείς που περιέχουν το γονίδιο της αναιμίας Fanconi A (FANCA) Lentivirális vektor mely a Fanconi-anémia A (FANCA) gént tartalmazza Vettore lentivirale contenente il gene dell anemia di Fanconi A (FANCA) Lentivīrusa vektors ar Fanconi anēmijas A (FANCA) gēnu Lentivirusinis vektorius, turintis Fankonio (Fanconi) anemijos A (FANCA) geną Vettur lentivirali li fih il-gene tal-anemija ta Fanconi A (FANCA) Wektor lentiwirusowy zawierający gen niedokrwistości A Fanconiego (FANCA) Vector lentiviral contendo o gene da anemia de Fanconi A (FANCA) Vector lentiviral ce conţine gena anemiei Fanconi A (FANCA) Lentivírusový vektor obsahujúci gén Fanconiho anémie A (FANCA) Lentivirusni vektor, ki vsebuje gen Fanconijeve anemije A (FANCA) Vector lentiviral conteniendo el gen de la anemia de Fanconi A (FANCA) Treatment of Fanconi anaemia type A Лечение на пациенти с подтип А на анемията на Фанкони Léčba Fanconiho anémie typu A Behandling af Fanconis anæmi type A Behandeling van Fanconi-anemie type A Fanconi aneemia tüübi A ravi Fanconin anemian tyypin A hoito Traitement de l anémie de Fanconi type A Behandlung der Fanconi-Anämie Gruppe A Θεραπεία ασθενών με αναιμία Fanconi τύπου Α A Fanconi-anémia A altípus kezelése Trattamento dell anemia di Fanconi tipo A Fankoni A tipa anēmijas ārstēšana Fanconi anemijos A tipo gydymas Kura tal-anemija ta Fanconi tat-tip A Leczenie niedokrwistości Fanconiego typu A Tratamento da anemia de Fanconi tipo A Tratamentul anemiei Fanconi tip A Liečba Fanconiho anémie typu A Zdravljenje Fanconijeve anemije tipa A Tratamiento de la anemia de Fanconi variante A 1 At the time of designation EMA/COMP/662962/2010 Page 4/5

Swedish Norwegian Icelandic Lentiviral vektor innehållande Fanconi anemi A (FANCA) -genen Lentiviral vektor som inneholder Fanconianemi A (FANCA)-genet Lentiveiru ferja sem inniheldur Fanconi blóðleysi A (FANCA) erfðavísi Behandling av Fanconis anemi typ A Behandling av Fanconis anemi type A Meðferð á Fanconi blóðleysi, gerð A EMA/COMP/662962/2010 Page 5/5