Public summary of opinion on orphan designation

Transcription

1 27 April 2016 EMA/COMP/164905/2016 Committee for Orphan Medicinal Products Adeno-associated viral vector serotype 8 encoding human ornithine transcarbamylase for the treatment of ornithine transcarbamylase deficiency On 21 March 2016, orphan designation (EU/3/16/1623) was granted by the European Commission to Pharma Gateway AB, Sweden, for adeno-associated viral vector serotype 8 encoding human ornithine transcarbamylase (also called DTX301) for the treatment of ornithine transcarbamylase deficiency. What is ornithine transcarbamylase deficiency? Ornithine transcarbamylase deficiency is one of the inherited disorders known as urea-cycle disorders, which cause ammonia to accumulate in the blood. Patients with ornithine transcarbamylase deficiency lack ornithine transcarbamylase, one of the liver enzymes needed to get rid of excess nitrogen. In the absence of this enzyme, excess nitrogen accumulates in the body in the form of ammonia, which can be harmful at high levels, especially to the brain. Symptoms of the disease usually appear in the first few days of life and include lethargy (lack of energy), vomiting, loss of appetite, seizures (fits) and coma. Ornithine transcarbamylase deficiency is a long-term debilitating and life-threatening disease that leads to altered brain function and is associated with poor overall survival. What is the estimated number of patients affected by the condition? At the time of designation, ornithine transcarbamylase deficiency affected approximately 0.1 in 10,000 people in the European Union (EU). This was equivalent to a total of around 5,000 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, sodium phenylbutyrate (Ammonaps) and glycerol phenylbutyrate (Ravicti) were authorised in the EU for the treatment of some urea-cycle disorders, including ornithine * 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 28), Norway, Iceland and Liechtenstein. This represents a population of 513,700,000 (Eurostat 2016). 30 Churchill Place Canary Wharf London E14 5EU United Kingdom Telephone +44 (0) Facsimile +44 (0) Send a question via our website An agency of the European Union European Medicines Agency, Reproduction is authorised provided the source is acknowledged.

2 transcarbamylase deficiency. In addition, patients were advised to control their dietary intake of proteins, which are rich in nitrogen, to reduce the amount of ammonia formed in the body. Liver transplantation was used to manage the condition in some people. The sponsor has provided sufficient information to show that a single dose of this medicine might be of significant benefit for patients with ornithine transcarbamylase deficiency because early laboratory studies showed a reduction in the production of ammonia. This assumption will need to be confirmed at the time of marketing authorisation, in order to maintain the orphan status. How is this medicine expected to work? This medicine is made of a virus that has been modified to contain the gene for the enzyme ornithine transcarbamylase, which is lacking in patients with ornithine transcarbamylase deficiency. When given by infusion (drip) to the patient, the virus is expected to carry the gene for ornithine transcarbamylase into the liver cells, enabling them to produce the missing enzyme for a long period. This is expected to reduce production of ammonia and prevent development of symptoms. The type of virus used in this medicine ( adeno-associated virus ) does not cause disease in humans. What is the stage of development of this medicine? At the time of submission of the application for orphan designation, the evaluation of the effects of this medicine in experimental models was ongoing. At the time of submission, no clinical trials with the medicine in patients with ornithine transcarbamylase deficiency had been started. At the time of submission, the medicine was not authorised anywhere in the EU for ornithine transcarbamylase deficiency 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 18 February 2016 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. 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. EMA/COMP/164905/2016 Page 2/5

3 For more information Sponsor s contact details: Contact details of the current sponsor for this orphan designation can be found on EMA website, on the medicine s rare disease designations page. 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/164905/2016 Page 3/5

4 Translations of the active ingredient and indication in all official EU languages 1, Norwegian and Icelandic Language Active ingredient Indication English Adeno-associated viral vector serotype 8 encoding human ornithine transcarbamylase Bulgarian Адено-свързан вирусен вектор серотип 8, кодиращ човешка орнитин транскарбамилаза Croatian Adeno-asocirani virusni vektor serotipa 8, kodiran za humanu ornitin-transkarbamilazu Czech Adeno-asociovaný virový vektor sérotypu 8 kódující lidskou ornitin transkarbamylázu Danish Adeno-associeret virus serotype 8 vektor, som koder for human ornithin transcarbamylase Dutch Adeno-geassocieerd virus serotype 8 vector die codeert voor humane ornithine transcarbamylase Estonian Adeno-assotsieerunud viirusvektor serotüüp 8, mis sisaldab inimese ornitiintranskarbamülaasi Finnish Adenoassosioitu virusvektori, serotyyppi 8, joka koodaa ihmisen ornitiinitranskarbamylaasia French Vecteur viral adéno-associé de sérotype 8 codant l ornithine transcarbamylase humaine German Adeno-assoziierter Viraler Vektor vom Serotyp 8, der für die humane Ornithin-Transcarbamylase codiert Greek Αδενο-σχετιζόμενος ιικός φορέας οροτύπου 8 που κωδικοποιεί την ανθρώπινη τρανσκαρβαμυλάση της ορνιθίνης Hungarian Humán ornitin transzkarbamilázt kódoló, 8-as szerotípusú, adeno-asszociált vírusvektor Italian Vettore virale adeno-associato di sierotipo 8 che codifica per l'ornitina-transcarbamilasi umana Latvian Adeno-asociētā vīrusa 8. serotipa vektors, kas kodē cilvēka ornitīna transkarbamilāzi Lithuanian Adenoasocijuoto viruso vektoriaus 8 serotipas, koduojantis žmogaus ornitintranskarbamoilazę Maltese Vettur imnissel mill-adenovirus tas-serotip 8 li jikkodifika ornithine transcarbamylase uman Polish Wektor wirusów zależnych od adenowirusów serotypu 8, kodujący ludzką transkarbamylazę ornitynową Portuguese Vector viral adeno-associado de serotipo 8 que codifica a ornitina-transcarbamilase humana Romanian Vector viral adeno-asociat de serotip 8, care codifică ornitin-transcarbamilaza umană Treatment of ornithine transcarbamylase deficiency Лечение на дефицит на орнитин транскарбамилаза Liječenje nedostatka ornitintranskarbamilaze Léčba nedostatku transkarbamylázy ornithine Behandling af ornithin transcarbamylase defect Behandeling van ornithine transcarbamylase deficiëntie Ornitiintranskarbamülaasi puudulikkuse ravi Ornitiinitranskarbamylaasin puutoksen hoito Traitement du déficit en ornithine transcarbamylase Behandlung des Ornithintranscarbamylase-Mangels Αγωγή για την έλλειψη της τρανσκαρβαμυλάσης της ορνιθίνης Ornitin transzkarbamiláz hiány kezelése Trattamento del deficit di ornitinatranscarbamilasi Ornitīna transkarbamilāzes nepietiekamības ārstēšana Ornitintranskarbamilazės stokos gydymas Kura ta' defiċjenza ta l-ornithine Transcarbamylase Leczenie pacjentów z niedoborem transkarbamylazy ornitynowej Tratamento da deficiência de ornitina-transcarbamilase Tratamentul deficitului de ornitintranscarbamilază 1 At the time of designation EMA/COMP/164905/2016 Page 4/5

5 Language Active ingredient Indication Slovak Adenovirusom pridruženi virusni vektor serotipa 8, ki kodira človeško ornitin-transkarbamilazo Slovenian Vektor adeno-pridruženega virusa serotipa 8, ki kodira človeško ornitin transkarbamilazo Spanish Vector viral adenoasociado del serotipo 8 que codifica la ornitinina transcarbamilasa humana Swedish Adenoassocierad virusvektor serotyp 8 som kodar för humant ornitintranskarbamylas Norwegian Adenoassosiert virus serotype 8 vektor, kodet for human ornitintranskarbamylase Icelandic Adenótengd veirugenaferja af sermisgerð 8 sem felur í sér manna ornitín transkarbamýlasa Liečba nedostatku transkarbamylázy ornitínu Zdravljenje pomanjkanja ornitintranskarbamilaze Tratamiento de la deficiencia de ornitina transcarbamilasa Behandling av brist på ornitintranskarbamylas Behandling av ornitintranskarbamylase-mangel Meðferð við skorti á ornitín transkarbamýlasa EMA/COMP/164905/2016 Page 5/5