Lists of medicinal products for rare diseases in Europe*

1 August 2021. Lists of medicinal products for rare diseases in Europe*. the General Table of contents PART 1: 3. 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 Annex 1: Orphan medicinal products withdrawn from the European Community Register of orphan medicinal products 23. Annex 2: Orphan medicinal products withdrawn from use in the European Union 32. Classificationby date of MA in descending order 34. Classification by ATC category 35. Classification by MA holder 36. PART 2 : 38. List of medicinal products intended for rare diseases in Europe with European marketing authorization without an orphan designation in Europe 38. Table of contents 38. Methodology 38. Classification by tradename 39. Classification by date of MA in descending order 107. Classification by ATC category 109. Classification by MA holder 111. For any questions or comments, please contact us: Orphanet Report Series - Lists of medicinal products for rare diseases in 2021.

2 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 Annex 1: Orphan medicinal products removed or withdrawn from the European Community Register of orphan medicinal products 23. Annex 2: Orphan medicinal products withdrawn from use in the European Union 32. Classificationby date of MA in descending order 34. Classification by ATC category 35. Classification by MA holder 36. 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 ( Authorisation (MA) at the date stated in the document. These eu/health/documents/community-register/h tml/. medicinal products may now be accessible in some, though ).

3 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.)

4 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 ( designation in Europe );. register/ ). *European Community marketing authorisation under the centralised procedure Orphanet Report Series - Lists of medicinal products for rare diseases in 2021. 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 or on the EMA website (European information on http://www. Medicines Agency) The EMA listing covers all medicinal products with Three additional Lists propose another classification by: marketing authorisation, not just orphan medicinal products .

5 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: Orphanet Report Series - Lists of medicinal products for rare diseases in 2021. 4. Classification by tradename TRADENAME ACTIVE SUBSTANCE MARKETING AUTHORISATION INDICATION MARKETING MARKETING. AUTHORISATION AUTHORISATION. DATE (DD/MM/YYYY) HOLDER. ABECMA idecabtagene Indicated for the treatment of adult patients 18/08/2021 Celgene Europe BV. vicleucel with relapsed and refractory multiple myeloma who have received at least three prior therapies, including an immunomodulatory agent, a proteasome inhibitor and an anti-CD38 antibody and have demonstrated disease progression on the last therapy 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.

6 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.

7 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 . Orphanet Report Series - Lists of medicinal products for rare diseases in 2021. 5. TRADENAME ACTIVE SUBSTANCE MARKETING AUTHORISATION INDICATION MARKETING MARKETING. AUTHORISATION AUTHORISATION. DATE (DD/MM/YYYY) HOLDER. 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 .

8 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. 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 -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 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) gastrointestinal stromal tumours (GIST).

9 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 anti-CD38. monoclonal antibody, and who have demonstrated disease progression on the last therapy Orphanet Report Series - Lists of medicinal products for rare diseases in 2021. 6. TRADENAME ACTIVE SUBSTANCE MARKETING AUTHORISATION INDICATION MARKETING MARKETING.

10 AUTHORISATION AUTHORISATION. DATE (DD/MM/YYYY) HOLDER. BLINCYTO blinatumomab Treatment of adults with Philadelphia 23/11/2015 Amgen Europe chromosome negative relapsed or refractory B -precursor acute lymphoblastic leukaemia (ALL). As monotherapy for the treatment of adults with Philadelphia chromosome negative CD19. positive B-precursor ALL in first or second complete remission with minimal residual disease (MRD) greater than or equal to As monotherapy for the treatment of paediatric patients aged 1 year or older with Philadelphia chromosome negative CD19. positive B cell precursor ALL which is refractory or in relapse after receiving at least two prior therapies or in relapse after receiving prior allogeneic hematopoietic stem cell transplantation. BRINEURA cerliponase alfa Treatment of neuronal ceroid lipofuscinosis 30/05/2017 BioMarin International type 2 (CLN2) disease , also known as Limited tripeptidyl peptidase 1 (TPP1) deficiency. BRONCHITOL mannitol Treatment of cystic fibrosis (CF) in adults 13/04/2012 Pharmaxis Europe aged 18 years and above as an add-on Limited therapy to best standard of care.