March 2021 Lists of medicinal products for rare diseases in Europe* the www.orpha.net www.orphadata.org General Table of contents PART 1: List of orphan medicinal products in Europe with European orphan designation and European marketing authorization 3 Table of contents 3 Methodology 3 Classification by tradename 5 Annex 1: Orphan medicinal products withdrawn from the European Community Register of orphan medicinal products 22 Annex 2: Orphan medicinal products withdrawn from use in the European Union 31 Classification by date of MA in descending order 33 Classification by ATC category 34 Classification by MA holder 35 PART 2 : 37 List of medicinal products intended for rare diseases in Europe with European marketing authorization without an orphan designation in Europe 37 Table of contents 37 Methodology 37 Classification by tradename 38 Classification by date of MA in descending order 104 Classification by ATC category 106 Classification by MA holder 108 For any questions or comments, please contact us: [email protected] Orphanet Report Series - Lists of medicinal products for rare diseases in Europe. March 2021 http://www.orpha.net/orphacom/cahiers/docs/GB/list_of_orphan_drugs_in_europe.pdf 2 PART 1: List of orphan medicinal products in Europe with European orphan designation and European marketing authorization* Table of contents List of orphan medicinal products in Europe with European orphan designation and European marketing authorisation* 3 Methodology 3 Classification by tradename 5 Annex 1: Orphan medicinal products removed or withdrawn from the European Community Register of orphan medicinal products 22 Annex 2: Orphan medicinal products withdrawn from use in the European Union 31 Classification by date of MA in descending order 33 Classification by ATC category 34 Classification by MA holder 35 Methodology This part of the document provides the list of all orphan with the list of medicinal products that have been granted a medicinal products that have received a European Marketing marketing authorization (http://ec.europa. Authorisation (MA) at the date stated in the document. These eu/health/documents/community-register/html/ medicinal products may now be accessible in some, though alfregister.htm). Both lists are available on the website of the not necessarily all, European countries. In reality, the DG Health and Food Safety (DG SANTE) of the European accessibility of a certain orphan medicinal product in a certain Commission. country depends on the strategy of the laboratory and the The first classification by tradename provides the name of decision taken by national health authorities concerning active substance, the marketing authorisation (MA) indication, reimbursement. Orphan medicinal products in Europe are the date of MA and the MA holder. This is followed by two medicinal products that have been granted a European annex tables providing: orphan designation (according to the Regulation (EC) No - list of orphan medicinal products withdrawn from the 141/2000), and then that have been granted a European Community Register of orphan medicinal products (see market authorisation and - if applicable - a positive evaluation Annex 1 - “Orphan medicinal products withdrawn from the of significant benefit. European Community Register of orphan medicinal The orphan medicinal products list in Europe, with orphan products”; their indications are detailed in Part II, “List of designation and European marketing authorisations, is medicinal products intended for rare diseases in Europe with determined by cross-referencing the list of medicinal European marketing authorisation without orphan products that have an orphan designation (http://ec.europa.eu/health/documents/community- designation in Europe”); register/html/alforphreg.htm) *European Community marketing authorisation under the centralised procedure Orphanet Report Series - Lists of medicinal products for rare diseases in Europe. March 2021 http://www.orpha.net/orphacom/cahiers/docs/GB/list_of_orphan_drugs_in_europe.pdf 3 - list of orphan medicinal products withdrawn from use in the Additional information can be found on each product in European Union (see Annex 2- “Orphan medicinal products the tab “Orphan drugs” on the Orphanet website withdrawn from use in the European Union”). More www.orpha.net or on the EMA website (European information on http://www. ema.europa.eu. Medicines Agency) http://www.ema.europa.eu. The EMA listing covers all medicinal products with Three additional lists propose another classification by: marketing authorisation, not just orphan medicinal products. Orphan medicinal products that have been - date of MA in descending order; granted a European orphan designation are indicated by - ATC category; the logo - MA holder. All the tradenames are presented in alphabetical order. Official and up to date information about orphan medicinal products is available in the Community Register of orphan medicinal products for human use: http://ec.europa.eu/health/documents/community-register/html/alforphreg.htm Orphanet Report Series - Lists of medicinal products for rare diseases in Europe. March 2021 http://www.orpha.net/orphacom/cahiers/docs/GB/list_of_orphan_drugs_in_europe.pdf 4 Classification by tradename TRADENAME ACTIVE SUBSTANCE MARKETING AUTHORISATION INDICATION MARKETING MARKETING AUTHORISATION AUTHORISATION DATE (DD/MM/YYYY) HOLDER ADAKVEO crizanlizumab Indicated for the prevention of recurrent vaso- 28/10/2020 Novartis Europharm occlusive crises (VOCs) in sickle cell disease Limited patients aged 16 years and older. It can be given as an add-on therapy to hydroxyurea /hydroxycarbamide (HU/HC) or as monotherapy in patients for whom HU/HC is inappropriate or inadequate. ADCETRIS brentuximab vedotin Indicated for adult patients with previously 25/10/2012 Takeda Pharma A/S untreated CD30+ Stage IV Hodgkin lymphoma (HL) in combination with doxorubicin, vinblastine and dacarbazine (AVD). Treatment of adult patients with relapsed or refractory CD30+ Hodgkin lymphoma (HL): -following autologous stem cell transplant (ASCT) or -following at least two prior therapies when ASCT or multi-agent chemotherapy is not a treatment option. Treatment of adult patients with CD30+ HL at increased risk of relapse or progression following ASCT Treatment of adult patients with relapsed or refractory systemic anaplastic large cell lymphoma (sALCL). Treatment of adult patients with CD30+ cutaneous T-cell lymphoma (CTCL) after at least 1 prior systemic therapy. ADEMPAS riociguat Treatment of adult patients with WHO 27/03/2014 Bayer AG Functional Class (FC) II to III with inoperable Chronic thromboembolic pulmonary hypertension (CTEPH), persistent or recurrent CTEPH after surgical treatment, to improve exercise capacity. As monotherapy or in combination with endothelin receptor antagonists, for the treatment of adult patients with pulmonary arterial hypertension (PAH) with WHO Functional Class (FC) II to III to improve exercise capacity. Efficacy has been shown in a PAH population including etiologies of idiopathic or heritable PAH or PAH associated with connective tissue disease. ALOFISEL darvadstrocel Treatment of complex perianal fistulas in adult 23/03/2018 Takeda Pharma A/S patients with non-active/mildly active luminal Crohn’s disease, when fistulas have shown an inadequate response to at least one conventional or biologic therapy. Alofisel should be used after conditioning of fistula. ALPROLIX eftrenonacog alfa Treatment and prophylaxis of bleeding in 12/05/2016 Swedish Orphan patients with haemophilia B (congenital Biovitrum AB (publ) factor IX deficiency). ALPROLIX can be used for all age groups. Orphanet Report Series - Lists of medicinal products for rare diseases in Europe. March 2021 http://www.orpha.net/orphacom/cahiers/docs/GB/list_of_orphan_drugs_in_europe.pdf 5 TRADENAME ACTIVE SUBSTANCE MARKETING AUTHORISATION INDICATION MARKETING MARKETING AUTHORISATION AUTHORISATION DATE (DD/MM/YYYY) HOLDER AMGLIDIA glibenclamide Treatment of neonatal diabetes mellitus, for 24/05/2018 Ammtek use in newborns, infants and children. Sulphonylureas like Amglidia have been shown to be effective in patients with mutations in the genes coding for the β-cell ATP-sensitive potassium channel and chromosome 6q24-related transient neonatal diabetes mellitus. ARIKAYCE amikacin indicated for the treatment of non- 27/10/2020 Insmed Netherlands B.V. LIPOSOMAL tuberculous mycobacterial (NTM) lung infections caused by Mycobacterium avium Complex (MAC) in adults with limited treatment options who do not have cystic fibrosis AYVAKYT avapritinib As monotherapy for the treatment of adult 24/09/2020 Blueprint Medicines patients with unresectable or metastatic (Netherlands) B.V. gastrointestinal stromal tumours (GIST) harbouring the platelet-derived growth factor receptor alpha (PDGFRA) D842V mutation BESPONSA inotuzumab As monotherapy for the treatment of adults 29/06/2017 Pfizer Europe MA EEIG ozogamicin with relapsed or refractory CD22-positive B cell precursor acute lymphoblastic leukaemia (ALL). Adult patients with Philadelphia chromosome positive (Ph+) relapsed or refractory B cell precursor ALL should have failed treatment with at least 1 tyrosine kinase inhibitor (TKI). BLENREP belantamab As monotherapy for the treatment of 25/08/2020 GlaxoSmithKline mafodotin multiple myeloma in adult patients, who (Ireland) Limited have received at least four prior therapies and whose disease is refractory to at least one proteasome inhibitor, one immunomodulatory agent, and an