Orphan medicinal products with marketing authorisation http://ec.europa.eu/health/documents/community-register/html/index_en.htm

List of Orphan Medicinal Products with Marketing Authorisation (as of 15 February 2021) N° CHMP + N° Medicinal New MA Sponsor Authorised Therapeutic Indication opinionsa productsb Product indic

2001

Fabrazyme (agalsidase Long-term replacement therapy in 1 1 Genzyme BV patients with a confirmed diagnosis of Fabry beta) disease (α-galactosidase A deficiency). EXPIRED

Replagal Shire Human (agalsidase Long-term enzyme replacement therapy in 2 2 Genetic patients with a confirmed diagnosis of Fabry alpha) Therapies AB disease (α-galactosidase A deficiency). EXPIRED

Treatment of adult and paediatric patients with newly diagnosed Philadelphia chromosome (bcrabl) positive (Ph+) chronic myeloid leukaemia (CML) for whom bone marrow transplantation is not considered as Glivec Novartis the first line of treatment. Glivec is also 3 3 (imatinib) Europharm indicated for the treatment of adult and EXPIRED Limited paediatric patients with Ph+ CML in chronic phase after failure of interferon-alpha therapy, or in accelerated phase or blast crisis. The effect of Glivec on the outcome of bone marrow transplantation has not been determined.

Glivec Novartis Glivec is also indicated for the treatment of adult patients with Kit (CD 117) positive 4 (imatinib) Europharm 2002 unresectable and/or metastatic malignant WITHDRAWN Limited gastrointestinal stromal tumours (GIST).

Glivec Novartis Treatment of adult patients with 5 (imatinib) Europharm unresectable recurrent and/or metastatic 2006 WITHDRAWN Limited dermafibrosarcoma protuberans

Glivec Novartis Treatment of adult patients with newly diagnosed Philadelphia chromosome positive 6 (imatinib) Europharm 2006 acute lymphoblastic leukaemia (Ph+ ALL) as WITHDRAWN Limited monotherapy

Glivec Novartis Treatment of adult patients with myelodysplastic/ myeloproliferative diseases 7 (imatinib) Europharm 2006 (MDS/MPD) associated with PDGFR gene re- WITHDRAWN Limited arrangement

Glivec Novartis Treatment of adult patients with 8 (imatinib) Europharm hypereosinophilic syndrome (HES) and 2006 WITHDRAWN Limited chronic eosinophilic leukaemia (CEL)

2002

"For induction of remission and consolidation in adult patients with Trisenox relapsed/refractory acute promyelocytic (arsenic Cephalon 9 4 leukaemia (APL), characterised by the trioxide) Europe presence of the t(15;17) translocation and/or EXPIRED the presence of the Pro-Myelocytic Leukaemia/Retinoic-Acid-Receptor-alpha (PML/RAR-alpha) gene. Previous treatment

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should have included a retinoid and chemotherapy. The response rate of other acute myelogenous leukaemia subtypes to TRISENOX has not been examined."

"Treatment of pulmonary arterial hypertension (PAH) to improve exercise capacity and symptoms in patients with WHO functional class III.Efficacy has been shown in: Tracleer Actelion - Primary (idiopathic and familial) PAH. 10 5 (bosentan) Registration - PAH secondary to scleroderma without significant interstitial pulmonary disease. EXPIRED Limited - PAH associated with congenital systemic- to-pulmonary shunts and Eisenmenger's physiology. - Some improvements have also been shown in patients with PAH WHO functional class II." Tracleer Actelion Indicated to reduce the number of new 11 (bosentan) Registration digital ulcers in patients with systemic 2007 WITHDRAWN Limited sclerosis and ongoing digital ulcer disease.

Treatment of patients with acromegaly who Somavert have had an inadequate response to surgery and/or radiation therapy and in whom an 12 6 (pegvisomant) Pfizer Limited appropriate medical treatment with EXPIRED somatostatin analogues did not normalize IGF-I concentrations or was not tolerated.

Zavesca is indicated for the oral treatment of Zavesca Actelion mild to moderate type 1 Gaucher disease. 13 7 () Registration Zavesca may be used only in the treatment of EXPIRED Limited patients for whom enzyme replacement therapy is unsuitable.

Extension of Indication – to include the Zavesca Actelion treatment of progressive neurological 14 (miglustat) Registration manifestations in adult patients and 2009 EXPIRED Limited paediatric patients with Niemann-Pick type C disease.

2003

Carbaglu Orphan Treatment of hyperammonaemia due to N- 15 8 () Europe Sarl acetylglutamate synthase deficiency. EXPIRED

This variation concerns an extension of Orphan Carbaglu indication of Carbaglu to add the treatment 16 Europe SARL - of hyperammoniemia due to isovaleric 2011 (carglumic acid) France acidaemia, methylmalonic acidaemia and propionic acidaemia. 6/2021

Aldurazyme is indicated for long-term Aldurazyme enzyme replacement therapy in patients with Genzyme a confirmed diagnosis of 17 9 (laronidase) Europe BV Mucopolysaccharidosis I (MPSI; a [alpha]-L- EXPIRED deficiency) to treat the non- neurological manifestations of the disease

Busilvex followed by cyclophosphamide (BuCy2) is indicated as conditioning treatment prior to conventional haematopoietic progenitor cell Busilvex Pierre Fabre transplantation (HPCT) in adult patients 18 10 (busulfan) Medicament when the combination is considered the best EXPIRED available option. Busilvex followed by cyclophosphamide (BuCy4) or melphalan (BuMel) is indicated as conditioning treatment prior to conventional haematopoietic progenitor cell 2

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transplantation in paediatric patients.

Ventavis Treatment of patients with primary pulmonary hypertension, classified as NYHA 19 11 (iloprost) Schering AG functional class III, to improve exercise EXPIRED capacity and symptoms.

Onsenal (celecoxib) For the reduction of the number of WITHDRAWN Pharmacia- adenomatous intestinal polyps in familial 20 12 adenomatous polyposis (FAP), as an adjunct FROM THE Pfizer EEIG to surgery and further endoscopic MARKET - surveillance. SAFETY

2004

Photobarr (porfimer sodium) Axcan Pharma Photodynamic therapy (PDT) with porfimer sodium is indicated for ablation of high grade 21 13 WITHDRAWN International dysplasia (HGD) in patients with Barrett’s FROM THE BV Esophagus (BE) MARKET - SAFETY

Litak Lipomed 22 14 (cladribine,B) Treatment of hairy cell leukaemia GmbH EXPIRED

Symptomatic treatment of advanced Lysodren Laboratoire (unresectable, metastatic or relapsed) 23 15 (mitotane) adrenal cortical carcinoma. The effect of HRA Pharma EXPIRED Lysodren on non-functional adrenal cortical carcinoma is not established.

Pedea Orphan Indicated to close a patent ductus arteriosus 24 16 (ibuprofen) Europe SARL in preterm newborn infants EXPIRED

Wilzin (zinc-acetate Orphan 25 17 Treatment of Wilson's disease dihydrate) Europe SARL EXPIRED

Reduction of elevated platelet counts in at Xagrid Shire risk essential thrombocythaemia patients (anegrelide who are intolerant to their current therapy or 26 18 Pharmaceutic hydrochloride) whose elevated platelet counts are not als Ltd EXPIRED reduced to an acceptable level by their current therapy.

2005

Treatment of chronic pain requiring Prialt Elan Pharma intrathecal (IT) analgesia in patients who fail 27 19 (ziconotide) to obtain adequate analgesia and/or suffer Int. EXPIRED intolerable adverse events with systemic opioids

Orfadin Treatment of patients with confirmed Swedish diagnosis of hereditary tyrosinemia type 1 28 20 () Orphan Int. (HT-1) in combination with dietary restriction EXPIRED of tyrosine and phenylalanine.

Xyrem (sodium UCB Pharma Treatment of narcolepsy with cataplexy in 29 21 oxybate) Ltd adult patients. WITHDRAWN

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Revatio Treatment of pulmonary arterial hypertension. Revatio has been shown to 30 22 (sidenafil Pfizer limited citrate) improve exercise ability and to reduce mean EXPIRED pulmonary arterial pressure

2006

Naglazyme (N- Long term enzyme replacement therapy in acetylgalactosa BioMarin patients with a confirmed diagnosis of 31 23 Mucopolysaccharidosis VI (MPS VI; (N- mine 4- Europe acetylgalactosamine 4-sulfatase deficiency; sulfatase,A) Maroteaux Lamy syndrome) EXPIRED

Myozyme is indicated for long-term enzyme Myozyme replacement therapy (ERT) in patients with a (recombinant confirmed diagnosis of Pompe disease (acid alpha-glucosidase deficiency). human acid Genzyme 32 24 alpha- Europe Myozyme is indicated in adults and glucosidase paediatric patients of all ages. EXPIRED In patients with late-onset Pompe disease the evidence of efficacy is limited

Treatment of acute lymphoblastic leukaemia (ALL) in paediatric patients who have Evoltra relapsed or are refractory after receiving at Genzyme least two prior regimens and where there is 33 25 (clofarabine) Europe BV no other treatment option anticipated to EXPIRED result in a durable response. Safety and efficacy have been assessed in studies of patients ≤ 21 years old at initial diagnosis

Nexavar For the treatment of patients with advanced (sorafenib Bayer renal cell carcinoma who have failed prior 34 26 interferon-alpha or interleukin-2 based tosylate) Healthcare AG therapy or are considered unsuitable for EXPIRED such therapy

Nexavar (sorafenib Bayer Extension of Indication to include treatment 35 2007 tosylate) Healthcare AG of hepatocellular carcinoma. EXPIRED

Extension of indication for the treatment of Nexavar patients with progressive, locally advanced or Bayer metastatic, differentiated 36 (sorafenib 2014 Healthcare AG (papillary/follicular/Hürthle cell) thyroid tosylate) carcinoma, refractory to radioactive iodine. 5/2024

Savene SpePharm 37 27 (dexrazoxane) Treatment of anthracycline extravasation Holding BV EXPIRED

Exjade (4-(3,5-Bis (hydroxiphenyl) Novartis Treatment of chronic iron overload due to blood transfusions (transfusion 38 28 -1,2,4) triazol- Europharm haemosiderosis) in adult and paediatric 1-yl)benzoic Limited patients (aged 2 years and over) acid, B) EXPIRED

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Treatment of adults with Philadelphia chromosome positive (Ph+) acute lymphoblastic leukaemia (ALL) and lymphoid Sprycel Bristol-Myers blast CML with resistance or intolerance to 39 29 (dasatinib) Squibb prior therapy. EXPIRED Pharma Treatment of adults with chronic, accelerated or blast phase chronic myeloid leukaemia (CML) with resistance or intolerance to prior therapy including imatinib mesilate.

Sutent is indicated for the treatment of advanced and/or metastatic renal cell carcinoma. Sutent Sutent is indicated for the treatment of 40 30 (sunitinib) Pfizer Ltd. unresectable and/or metastatic malignant WITHDRAWN gastrointestinal stromal tumour (GIST) after failure of imatinib mesylate treatment due to resistance or intolerance.

Thelin Treatment of patients with pulmonary (sitaxentan arterial hypertension classified as WHO sodium) functional class III, to improve exercise 41 31 WITHDRAWN Pfizer Limited. capacity. Efficacy has been shown in FROM THE primarily pulmonary hypertension and in pulmonary hypertension associated with MARKET - connective tissue disease. SAFETY 2007

Indicated for use in conjunction with clobazam and valproate as adjunctive Diacomit therapy of refractory generalized tonic-clonic 42 32 (stiripentol) BIOCODEX seizures in patients with severe myoclonic EXPIRED epilepsy in infancy (SMEI, Dravet’s syndrome) whose seizures are not adequately controlled with clobazam and valproate.

"Elaprase is indicated for the long-term Elaprase Shire Human treatment of patients with Hunter syndrome (iduronate-2- Genetic 43 33 (Mucopolysaccharidosis II, MPS II). sulfatase) Therapies AB - EXPIRED Sweden Heterozygous females were not studied in the clinical trials."

Inovelon Adjunctive therapy in the treatment of 44 34 (rufinamide) Esai Limited seizures associated with Lennox-Gastaut EXPIRED syndrome in patients 4 years and older.

Adjunctive treatment of homocystinuria, involving deficiencies or defects in: - cystathionine beta-synthase (CBS), - 5,10-methylene-tetrahydrofolate reductase Cystadane (MTHFR), (betaine Orphan 45 35 - cobalamin cofactor (cbl). anhydrous A) Europe

EXPIRED Cystadane should be used as supplement to other therapies such as vitamin B6 (pyridoxine), vitamin B12 (cobalamin), folate and a specific diet.

Revlimid is indicated for the treatment of adult patients with previously untreated multiple myeloma who are not eligible for Revlimid Celgene transplant. 46 36 (lenalidomide) Europe Ltd EXPIRED Revlimid in combination with dexamethasone is indicated for the treatment of multiple myeloma in adult patients who have received at least one prior therapy.

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Revlimid is indicated for the treatment of patients with transfusion-dependent Celgene Revlimid anaemia due to low- or intermediate-1-risk 47 Europe myelodysplastic syndromes associated with 2013 (lenalidomide) Limited an isolated deletion 5q cytogenetic abnormality when other therapeutic options are insufficient or inadequate. 06/2023

Celgene Revlimid Revlimid as monotherapy is indicated for the 48 Europe treatment of adult patients with relapsed or 2016 (lenalidomide) Limited refractory mantle cell lymphoma 07/2026

Indicated in adults and children for the treatment of patients with paroxysmal Soliris Alexion nocturnal haemoglobinuria (PNH). Evidence 49 37 (eculizumab) of clinical benefit demonstrated in patients Europe EXPIRED with haemolysis with clinical symptom(s) indicative of high disease activity, regardless of transfusion history

Alexion Soliris Extension Of Indication for atypical 50 Europe SAS - haemolytic uremic syndrome (aHUS) 2011 (eculizumab) France 11/2023

Alexion Extension Of Indication for Refractory Soliris generalized myasthenia gravis (gMG) in 51 Europe SAS - 2017 (eculizumab) patients who are anti-acetylcholine receptor France (AChR) antibody-positive 08/2027

"Indicated for the prevention of recurrent Siklos Addmedica painful vaso-occlusive crises including acute 52 38 (hydroxycarba chest syndrome in adults, adolescents and SAS - France mide) children older than 2 years suffering from symptomatic Sickle Cell Syndrome."

Long-term treatment of growth failure in children and adolescents with severe primary insulin like growth factor-1 deficiency (Primary IGFD). Severe Primary IGFD is defined by: • height standard deviation score ≤ –3.0 and • basal IGF-1 levels below the 2.5th percentile for age and gender and • GH sufficiency. • Exclusion of secondary forms of IGF-1 Increlex deficiency, such as malnutrition, 53 39 (mecasermin) Ipsen Pharma hypothyroidism, or chronic treatment with EXPIRED pharmacologic doses of anti-inflammatory steroids. Severe Primary IGFD includes patients with mutations in the GH receptor (GHR), post- GHR signalling pathway, and IGF-1 gene defects; they are not GH deficient, and therefore, they cannot be expected to respond adequately to exogenous GH treatment. It is recommended to confirm the diagnosis by conducting an IGF-1 generation test.

Treatment of patients with T-cell acute lymphoblastic leukaemia (T-ALL) and T-cell lymphoblastic lymphoma (T-LBL) whose Atriance disease has not responded to or has relapsed Glaxo Group 54 40 (nelarabine) following treatment with at least two Ltd EXPIRED chemotherapy regimens. Due to the small patient populations in these disease settings, the information to support these indications is based on limited data.

Gliolan Visualisation of malignant tissue during 55 41 Medac GmbH (5 surgery for malignant glioma aminolevulinic

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acid hydrochloride L) EXPIRED

Treatment of patients with advanced soft Yondelis tissue sarcoma, after failure of PharmaMar anthracyclines and ifosfamide, or who are 56 42 (trabectedin) SA unsuited to receive these agents. Efficacy EXPIRED data are based mainly on liposarcoma and leiomyosarcoma patients

EXTENSION OF INDICATION Indicated for the treatment of patients with advanced soft tissue sarcoma, after failure of Yondelis anthracyclines and ifosfamide, or who are PharmaMar unsuited to receive these agents. Efficacy 57 (trabectedin) 2009 SA data are based mainly on liposarcoma and EXPIRED leiomyosarcoma patients. In combination with pegylated liposomal doxorubicin (PLD) is indicated for the treatment of patients with relapsed platinum-sensitive ovarian cancer. Torisel First-line treatment of patients with 58 43 (temsirolimus) Pfizer Limited advanced renal cell carcinoma who have at EXPIRED least three of six prognostic risk factors.

Torisel EXTENSION OF INDICATION to include 59 (temsiroliums) Pfizer Limited treatment of adult patients with relapsed 2009 EXPIRED and/or refractory mantle cell lymphoma.

Treatment of Philadelphia chromosome Tasigna Novartis positive chronic myelogenous leukaemia 60 44 (nilotinib) Europharm (CML) – 2 additional years of market EXPIRED Ltd exclusivity as paediatric reward granted on 17 Nov 2017 – will expire in

2008

Thalidomide Thalidomide Celgene in combination with Celgene Celgene melphalan and prednisone as first line 61 45 Europe treatment of patients with untreated multiple (thalidomide) Limited myeloma, aged ≥ 65 years or ineligible for EXPIRED high dose chemotherapy.

Volibris Treatment of patients with pulmonary Glaxo Group arterial hypertension (PAH) classified as 62 46 (ambrisentan) Ltd WHO functional class II and III, to improve EXPIRED exercise capacity.

Firazyr Indicated for symptomatic treatment of acute Shire Orphan (icatibant attacks of hereditary angioedema (HAE) in 63 47 Therapies adults (with C1-esterase-inhibitor acetate L) GmbH deficiency). - 2 additional years of market EXPIRED exclusivity as paediatric reward granted

Ceplene maintenance therapy is indicated for Ceplene adult patients with acute myeloid leukaemia (histamine in first remission concomitantly treated with 64 48 Meda AB dihydrochloride interleukin-2 (IL-2). The efficacy of Ceplene ) EXPIRED has not been fully demonstrated in patients older than age 60.

Treatment of hyperphenylalaninaemia (HPA) in adult and paediatric patients of 4 years of Kuvan age and over with phenylketonuria (PKU) Merck Serono (sapropterin who have been shown to be responsive to 65 49 Europe dihydrochloride such treatment. Kuvan is also indicated for Limited ) the treatment of hyperphenylalaninaemia (HPA) in adult and paediatric patients with (BH4) deficiency who have been shown to be responsive to such

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treatment. 2 additional years of market exclusivity as paediatric reward granted on 24/06/2015-expires

Treatment of adult patients who are not eligible for haematopoietic stem cell transplantation with:  intermediate-2 and high-risk myelodysplastic syndromes (MDS) according to the International Prognostic Celgene Vidaza Scoring System (IPSS), Europe Ltd- 66 50 (azacitidine)  chronic myelomonocytic leukaemia United (CMML) with 10-29% marrow blasts EXPIRED Kingdom without myeloproliferative disorder,  acute myeloid leukaemia (AML) with 20-30% blasts and multi-lineage dysplasia, according to World Health Organisation (WHO) classification.

2009

Indicated for adult chronic immune (idiopathic) thrombocytopenic purpura (ITP) Nplate splenectomised patients refractory to other Amgen Europe 67 51 (romiplostim) treatments (e.g. corticosteroids, BV immunoglobulins). Nplate may be considered EXPIRED as second line treatment for adult non- splenectomised patients where surgery is contra-indicated. Indicated in children, adolescents and Mepact young adults for the treatment of high-grade Takeda France resectable non-metastatic osteosarcoma after 68 52 (mifamurtide) SAS macroscopically complete surgical resection. EXPIRED It is used in combination with post-operative multi-agent chemotherapy

Peyona Chiesi (previously 69 53 Farmaceutici Treatment of primary apnoea of premature F Nymusa, S.P.A. - Italy caffeine citrate

Indicated in combination with G-CSF to enhance mobilisation of haematopoietic stem Mozobil Genzyme BV cells to the peripheral blood for collection 70 54 (plerixafor) The and subsequent autologous transplantation EXPIRED Netherlands in adults patients with lymphoma and multiple myeloma whose cells mobilise poorly.

Cayston (aztreonam Gilead Suppressive therapy of chronic pulmonary Sciences infections due to Pseudomonas aeruginosa in 71 55 lysinate inhalation use) International patients with cystic fibrosis (CF) aged 6 years Ltd – UK and older. EXPIRED

Rilonacept Regeneron (formerly Treatment of Cryopyrin-Associated Periodic Arcalyst; Syndromes (CAPS) including Familial Cold 72 56 rilonacept) Regeneron UK Autoinflammatory Syndrome (FCAS) and WITHDRAWN Muckle-Wells Syndrome (MWS) in adults and FROM THE children aged 12 years and older. MARKET – SAFETY

Firdapse BioMarin Symptomatic treatment of Lambert-Eaton 73 57 (amifampridine) Europe Ltd myasthenic syndrome (LEMS) in adults. EXPIRED

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Indicated for adult chronic immune GlaxoSmithKli (idiopathic) thrombocytopenic purpura (ITP) Revolade ne Trading splenectomised patients who are refractory to other treatments (e.g. corticosteroids, 74 58 (eltrombopag) Services immunoglobulins). Revolade may be WITHDRAWN Limited – considered as second line treatment for adult Ireland non-splenectomised patients where surgery is contraindicated.

Novartis Treatment of patients with advanced renal Afinitor cell carcinoma, whose disease has 75 59 Europharm (everolimus) progressed on or after treatment with VEGF- WITHDRAWN Ltd targeted therapy.

Treatment of Cryopyrin-Associated Periodic Syndromes (CAPS) in adults, adolescents and children aged 4 years and older with body weight above 15 kg, including Muckle- Novartis Wells Syndrome (MWS), Neonatal-Onset Ilaris Multisystem Inflammatory Disease (NOMID) 76 60 Europharm (canakinumab) / Chronic Infantile Neurological, Cutaneous, WITHDRAWN Ltd. Articular Syndrome (CINCA), Severe forms of Familial Cold Autoinflammatory Syndrome (FCAS) / Familial Cold Urticaria (FCU) presenting with signs and symptoms beyond cold-induced urticarial skin rash.

2010

Indicated, in combination with other chemotherapy medicinal products: 1) with or without total body irradiation (TBI), as conditioning treatment prior to allogeneic or autologous haematopoietic Tepadina Adienne S.r.l - progenitor cell transplantation (HPCT) in 77 61 (thiotepa) Italy haematological diseases in adult and paediatric patients; 2) when high dose chemotherapy with HPCT support is appropriate for the treatment of solid tumours in adult and paediatric patients."

Refractory chronic lymphocytic leukaemia Arzerra (CLL): Glaxo Group 78 62 (ofatumumab) Limited - UK Arzerra is indicated for the treatment of CLL WITHDRAWN in patients who are refractory to fludarabine and alemtuzumab

Previously untreated chronic lymphocytic leukaemia (CLL): Arzerra Glaxo Group Arzerra in combination with chlorambucil or 79 (ofatumumab) 2014 Limited - UK bendamustine is indicated for the treatment WITHDRAWN of patients with CLL who have not received prior therapy and who are not eligible for fludarabine-based therapy.

Shire Treatment of type 1 Gaucher disease. 2 VPRIV Pharmaceutic additional years of market exclusivity as 80 63 (velaglucerase als Ireland paediatric reward granted on 29/08/2016 alfa) Limited – Ireland 08/2022

2011

Esbriet InterMune UK Treatment for adults with idiopathic 81 64 (perfenidone) Ltd. pulmonary fibrosis 03/2021

TOBI podhaler Novartis Suppressive therapy of chronic pulmonary 82 65 infection due to Pseudomonas aeruginosa in (tobramycin) Europharm adults and children aged 6 years and older

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Limited with cystic fibrosis 07/2023

Treatment of patients aged 3 years and older with subependymal giant cell astrocytoma Novartis (SEGA) associated with tuberous sclerosis 83 66 Votubia Europharm complex (TSC) who require therapeutic (everolimus) Limited intervention but are not amenable to surgery 09/2021

Plenadren (hydrocortisone ViroPharma Treatment for adults with adrenal 84 67 (modified SPRL insufficiency 11/2021 release tablet)

Vyndaqel Pfizer Limited Treatment of transthyretin amyloidosis in 85 68 adult patients with symptomatic (tafamidis) - UK polyneuropathy 11/2021

2012

Xaluprine (previously known as Nova Mercaptopurine Treatment of acute lymphoblastic leukaemia 86 69 Laboratories (ALL) in adults, adolescents and children Nova Limited - UK 03/2022 Laboratories and Novapurine)

Pharmaxis Bronchitol Treatment of cystic fibrosis in adults aged 18 87 70 Pharmaceutic years and above as an add-on therapy to (manitolum) als best standard of care 04/2022

Novartis Signifor Treatment of adult patients with Cushing’s 88 71 Europharm disease for whom surgery is not an option or (pasireotide) Limited UK for whom surgery has failed 04/2022

Treatment of adult patients with acromegaly Novartis Signifor for whom surgery is not an option or has not 89 Europharm been curative and who are inadequately 2014 (pasireotide) Limited UK controlled on treatment with another somatostatin analogue 11/2024

Vertex Kalydeco Pharmaceutic Treatment of cystic fibrosis (CF) in patients 90 72 aged 12 months (granules) and older who ivacaftor als (U.K.) have mutation in the CFTR gene 07/2022 Limited

Treatment of disease related splenomegaly or Novartis symptoms in adult patients with primary Jakavi myelofibrosis (also known as chronic 91 73 Europharm (ruxolitinib) idiopathic myelofibrosis), post polycythaemia WITHDRAWN Limited - UK vera myelofibrosis or post essential thrombocythaemia myelofibrosis.

NPS Pharma Treatment of patients aged 1 year and above with Short Bowel Syndrome. Patients 92 74 Revestive Holdings () should be stable following a period of Limited intestinal adaptation after surgery 09/2022

Long-term prophylactic treatment of bleeding NovoThirteen Novo Nordisk in adult and paediatric patients 6 years and 93 75 (catridecacog) A/S above with congenital factor-XIII-A-subunit WITHDRAWN deficiency.

Treatment of adult patients aged 65 years Janssen-Cilag Dacogen and above with newly diagnosed de novo or 94 76 International (decitabine) secondary acute myeloid leukaemia (AML), NV - Belgium according to the WHO classification, who are not candidates for standard induction

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chemotherapy” 09/2022

Glybera (adeno- Glybera is indicated for adult patients diagnosed with familial lipoprotein lipase associated viral uniQure deficiency (LPLD) and suffering from severe vector biopharma or multiple pancreatitis attacks despite 95 77 expressing B.V. - The dietary fat restrictions. The diagnosis of lipoprotein Netherlands LPLD has to be confirmed by genetic testing. lipase The indication is restricted to patients with detectable levels of LPL protein. WITHDRAWN

Adcetris is indicated for the treatment of adult patients with relapsed or refractory Adcetris Takeda CD30+ H83 (Hodgkin’s lymphoma): 96 78 (brentuximab Pharma A/S, 1.following autologous stem-cell transplant vedotin) Danmark (ASCT) or; 2.following at least two prior therapies when ASCT or multi-agent chemotherapy is not a treatment option 10/2022 Adcetris Takeda Adcetris is indicated for the treatment of 97 (brentuximab Pharma A/S, adult patients with relapsed or refractory vedotin) Danmark systemic anaplastic large cell lymphoma (sALCL) 10/2022 Adcetris Takeda ADCETRIS is indicated for the treatment of 98 (brentuximab Pharma A/S, adult patients with CD30+ cutaneous T-cell 2017 vedotin) Danmark lymphoma (CTCL) after at least 1 prior systemic therapy 12/2027 NexoBrid (concentrate of MediWound proteolytic NexoBrid is indicated for removal of eschar 99 79 Germany in adults with deep partial- and full- GmbH thickness thermal burns 12/2022 enriched in bromelain)

2013

Bosulif Pfizer Limited 100 80 (bosutinib) United Treatment of chronic myeloid leukaemia WITHDRAWN Kingdom

Iclusig is indicated in adult patients with: 1) chronic-phase, accelerated-phase or blast- ARIAD Iclusig phase chronic myeloid leukaemia (CML) who 101 81 Pharma Ltd - are resistant to dasatinib or nilotinib, who (ponatinib) UK are intolerant to dasatinib or nilotinib and for whom subsequent treatment with imatinib is not clinically appropriate, or who have the T315I mutation; 07/2023 2) Philadelphia-chromosome-positive acute lymphoblastic leukaemia (Ph+ ALL) who are ARIAD Iclusig resistant to dasatinib, who are intolerant to 102 Pharma Ltd - (ponatinib) dasatinib and for whom subsequent UK treatment with imatinib is not clinically appropriate, or who have the T315I mutation 07/2023 Pomalidomide Celgene in combination with Imnovid dexamethasone is indicated in the treatment (previously Celgene of adult patients with relapsed and refractory multiple myeloma who have received at least 103 82 Pomalidomide Europe two prior treatment regimens, including both Celgene; Limited - UK lenalidomide and bortezomib, and have pomalidomide) demonstrated disease progression on the last therapy 08/2023

Procysbi Raptor Probysbi is indicated for the treatment of 104 83 ( Pharmaceutic proven nephropathic cystinosis. Cysteamine bitartrate) als Europe BV reduces cystine accumulation in some cells - The (e.g. leukocytes, muscle and liver cells) of 11

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Netherlands nephropathic cystinosis patients and, when treatment is started early, it delays the development of renal failure 08/2023

Orphacol is indicated for the treatment of inborn errors in primary bile-acid synthesis due to 3β-hydroxy-Δ5-C27-steroid Orphacol Laboratoires 105 84 oxidoreductase deficiency or Δ4-3-oxosteroid- (cholic acid) CTRS 5β-reductase deficiency in infants, children and adolescents aged 1 month to 18 years and adults 09/2023

Defitelio is indicated for the treatment of severe hepatic veno-occlusive disease (VOD) also known as sinusoidal obstructive Defitelio Gentium syndrome (SOS) in haematopoietic stem-cell 106 85 (defibrotide) S.p.A. - Italy transplantation (HSCT) therapy. It is indicated in adults and in adolescents, children and infants over 1 month of age 10/2023

Opsumit, as monotherapy or in combination, Janssen-Cilag Opsumit is indicated for the long-term treatment of 107 86 International pulmonary arterial hypertension (PAH) in (macitentan) NV adult patients of WHO Functional Class (FC) II to III 12/2023

Jinarc Otsuka Autosomal dominant polycystic kidney 108 87 (tolvaptan) Pharmaceutic disease WITHDRAWN al Europe Ltd

2014

Indicated for use as part of an appropriate Janssen-Cilag combination regimen for pulmonary Sirturo multidrug resistant tuberculosis (MDR TB) in 109 88 International (bedaquiline adult patients when an effective treatment fumarate) N.V. Belgium regimen cannot otherwise be composed for reasons of resistance or tolerability 03/2024

Treatment of adult patients with progressive, 110 89 Cometriq TMC Pharma unresectable locally advanced or metastatic (cabozantinib) medullary thyroid carcinoma 03/2024

Treatment of adult patients with Chronic Bayer Pharma thromboembolic pulmonary hypertension 111 90 Adempas (riociguat) AG (CTEPH) and Pulmonary arterial hypertension (PAH) 03/2024

FGK Kolbam Representative 112 91 (cholic acid) Inborn errors in primary bile-acid synthesis Service GmbH, WITHDRAWN Germany

Inborn errors in primary bile-acid synthesis due to Sterol 27-hydroxylase (presenting as cerebrotendinous xanthomatosis, CTX) Kolbam Retrophin deficiency, 2- (or α-) methylacyl-CoA 113 2015 (cholic acid) Europe Ltd racemase (AMACR) deficiency or Cholesterol 7α-hydroxylase (CYP7A1) deficiency in infants, children and adolescents aged 1 month to 18 years and adults 11/2025

Granupas (previously Treatment of tuberculosis in adults and Lucane para- paediatric patients from 28 days of age and 114 92 Pharma SA - older when an effective treatment regimen aminosalicylic France cannot otherwise be composed for reasons of acid Lucane or resistance or tolerability 04/2024 PAS-GR)

Deltyba Otsuka Novel Treatment of multidrug-resistant 115 93 (delamanid) Products tuberculosis (MDR-TB) in adults 04/2024 GmbH - 12

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Germany

Vimizim BioMarin Treatment of mucopolysaccharidosis, type 116 94 IVA (Morquio A Syndrome, MPS IVA) in (elosulfase alfa) Europe Ltd patients of all ages 04/2024

Treatment of adult patients with multicentric Janssen-Cilag Castleman’s disease (MCD who are human 117 95 Sylvant International immunodeficiency virus (HIV) negative and (siltuximab) NV human herpesvirus-8 (HHV-8) negative 05/2024

Gazyvaro in combination with chlorambucil Roche is indicated for the treatment of adult patients with previously untreated chronic 118 96 Gazyvaro Registration (obinutuzumab) lymphocytic leukaemia (CLL) and with Ltd comorbidities making them unsuitable for full-dose fludarabine based therapy 07/2024

Gazyvaro in combination with chemotherapy, Roche followed by Gazyvaro maintenance therapy in patients achieving a response, is indicated 119 Gazyvaro Registration 2016 (obinutuzumab) for the treatment of patients with previously Ltd untreated advanced Follicular lymphoma FL 06/2026

Translarna is indicated for the treatment of Duchenne muscular dystrophy resulting from a nonsense mutation in the dystrophin PTC gene, in ambulatory patients aged 5 years 120 97 Translarna Therapeutics and older. Efficacy has not been (ataluren) Limited demonstrated in non-ambulatory patients. The presence of a nonsense mutation in the dystrophin gene should be determined by genetic testing 08/2024

Janssen-Cilag Imbruvica is indicated for the treatment of 121 98 Imbruvica International adult patients with relapsed or refractory (ibrutinib) NV mantle cell lymphoma (MCL) 10/2024

Imbruvica is indicated for the treatment of adult patients with chronic lymphocytic Janssen-Cilag leukaemia (CLL) who have received at least 122 Imbruvica International one prior therapy, or in first line in the (ibrutinib) NV presence of 17p deletion or TP53 mutation in patients unsuitable for chemo immunotherapy 10/2024

Imbruvica is indicated for the treatment of Janssen-Cilag adult patients with Waldenström’s macroglobulinaemia (WM) who have received 123 Imbruvica International 2015 (ibrutinib) at least one prior therapy, or in first line NV treatment for patients unsuitable for chemo- immunotherapy 07/2025

Ketoconazole HRA is indicated for the Ketoconazole Laboratoire treatment of endogenous Cushing’s 124 99 HRA HRA Pharma syndrome in adults and adolescents above (ketoconazole) the age of 12 years 11/2024

Lynparza is indicated as monotherapy for the maintenance treatment of adult patients with platinum-sensitive relapsed BRCA-mutated Lynparza AstraZeneca (germline and/or somatic) high grade serous 125 100 (olaparib) AB epithelial ovarian, fallopian tube, or primary WITHDRAWN peritoneal cancer who are in response (complete response or partial response) to platinum-based chemotherapy

In combination with paclitaxel is indicated Cyramza Eli Lilly for the treatment of adult patients with 126 101 (ramucirumab) Nederland advanced gastric cancer or gastro- WITHDRAWN B.V. oesophageal junction adenocarcinoma with disease progression after prior platinum and

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fluoropyrimidine chemotherapy. Monotherapy is indicated for the treatment of adult patients with advanced gastric cancer or gastro-oesophageal junction adenocarcinoma with disease progression after prior platinum or fluoropyrimidine chemotherapy, for whom treatment in combination with paclitaxel is not appropriate.

Clinuvel UK Prevention of phototoxicity in adult patients 127 102 Scenesse with erythropoietic protoporphyria (EPP) (afamelanotide) Limited 12/2024

2015

Boehringer Ingelheim Ofev is indicated in adults for the treatment 128 103 Ofev of Idiopathic Pulmonary Fibrosis (IPF) (nibtedanib) Pharma GmbH 01/2025 & Co. KG

Cerdelga is indicated for the long-term treatment of adult patients with Gaucher Genzyme disease type 1 (GD1), who are CYP2D6 poor 129 104 Cerdelga () Europe BV metabolisers (PMs), intermediate metabolisers (IMs) or extensive metabolisers (EMs) 01/2025

Treatment of adult patients with moderate to Holoclar severe limbal stem cell deficiency (defined by (ex vivo the presence of superficial corneal expanded Chiesi neovascularisation in at least two corneal quadrants, with central corneal involvement, 130 105 autologous Farmaceutici and severely impaired visual acuity), human corneal S.p.A. epithelial cells unilateral or bilateral, due to physical or containing chemical ocular burns. A minimum of 1-2 mm2 of undamaged limbus is required for stem cells) biopsy 02/2025

Lenvima is indicated for the treatment of Lenvima adult patients with progressive, locally Eisai Europe advanced or metastatic, differentiated 131 106 (lenvatinib mesylate) Ltd (papillary/follicular/Hürthle cell) thyroid WITHDRAWN carcinoma (DTC), refractory to radioactive iodine (RAI) Lenvima Eisai Europe Lenvima is indicated as monotherapy for the 132 (lenvatinib treatment of adult patients with advanced or mesylate) Ltd unresectable hepatocellular carcinoma (HCC) WITHDRAWN Vanda Hetlioz is indicated for the treatment of Non- 133 107 Hetlioz Pharmaceutic 24-Hour Sleep-Wake Disorder (Non-24) in (tasimelteon) als Ltd totally blind adults 07/2025

Unituxin is indicated for the treatment of high-risk neuroblastoma in children aged 12 months to 17 years. who have previously United received induction chemotherapy and Unituxin achieved at least a partial response, followed 134 108 Therapeutics (dinutuximab) by myeloablative therapy and autologous WITHDRAWN Europe Ltd stem cell transplantation. It is administered in combination with granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin-2 (IL-2), and isotretinoin

Synageva Kanuma is used to treat patients of all ages 135 109 Kanuma BioPharma with lysosomal acid lipase deficiency 9/2025 () Ltd

Novartis Farydak is indicated in combination with 136 110 Farydak Europharm bortezomib and dexamethasone, for the (panobinostat ) Ltd treatment of relapsed and/or refractory multiple myeloma in adults patients who 14

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have received at least two prior regimens including bortezomib and an immunomodulatory agent 9/2025

Strensiq is indicated for long-term enzyme Alexion replacement therapy in patients with 137 111 Strensiq paediatric-onset hypophosphatasia to treat () Europe SAS the bone manifestations of the disease 9/2025

Santera Raxone is indicated for the treatment of visual impairment in adolescent and adult 138 112 Raxone Pharmaceutic (ibedenone) patients with Leber’s Hereditary Optic als Gmbh Neuropathy 10/2025

Basilea Cresemba is indicated for the treatment of 139 113 Cresemba (isavuconazole) Medical Ltd adults with invasive aspergillosis 10/2025

Basilea Treatment of mucormycosis in patients for 140 Cresemba whom amphotericin B is inappropriate (isavuconazole) Medical Ltd 10/2025

Amgen Europe Kyprolis is indicated for the treatment of 141 114 Kyprolis adult patients with multiple myeloma (carfilzomib) BV 11/2025

Orkambi Vertex Orkambi is indicated for the treatment of 142 115 (lumacaftor/ Pharmaceutic cystic fibrosis ivacaftor) als WITHDRAWN Baxalta Obizur Obizur is indicated for the treatment of 143 116 Innovations (susoctog alfa) haemophilia A WITHDRAWN GmbH Elocta Biogen Idec Elocta is indicated for the treatment of 144 117 (efmoroctocog alfa) Ltd haemophilia A WITHDRAWN Blincyto is indicated as monotherapy for the treatment of paediatric patients aged 1 year or older with Philadelphia chromosome Amgen Europe negative CD19 positive B‑precursor ALL 145 118 Blincyto which is refractory or in relapse after (blinatumomab) B.V. receiving at least two prior therapies or in relapse after receiving prior allogeneic hematopoietic stem cell transplantation 11/2025

Horizon Ravicti is indicated for the treatment of Ravicti inborn urea cycle disorders (UCDs), 146 119 Therapeutics (glycerol including CPS, OTC, ASS, ASL, ARG and phenylbutyrate) Limited HHH 11/2025 Quinsair 147 120 (levofloxacin) Regintel Cystic fibrosis WITHDRAWN 2016

Treatment and prophylaxis of bleeding Coagadex Bio Products episodes and for perioperative 148 121 (human Laboratory management in all age groups patients coagulation limited with hereditary factor X deficiency factor X) 03/2026

Wakix is indicated in adults for the Bioprojet 149 122 Wakix treatment of narcolepsy with or without Pharma (pitolisant) cataplexy 04/2026

Idelvion CSL Behring Treatment and prophylaxis of bleeding 150 123 (albutrepenona GmbH in all age groups patients with cog alfa) haemophilia B (congenital factor IX

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deficiency) 06/2026

Uptravi Actelion 151 124 (selexipag) Registration Pulmonary arterial hypertension WITHDRAWN Ltd

Treatment and prophylaxis of bleeding Biogen Idec in all age groups patients with 152 125 Alprolix (eftrenacog alfa) Ltd haemophilia B (congenital factor IX deficiency) 05/2026

Janssen-Cilag Treatment of plasma cell myeloma in 153 126 Darzalex International adults patients 05/2026 (daratumumab) N.V. Galafold is indicated for long-term treatment of adults and adolescents Galafold Amicus aged 16 years and older with a 154 127 (migalastat Therapeutics confirmed diagnosis of Fabry disease (α- hydrochloride) UK Ltd galactosidase A deficiency) and who have an amenable mutation 05/2026 Strimvelis (autologous CD34+ + cells transduced GlaxoSmithKli Severe combined immunodeficiency due with retroviral ne Trading 155 128 to adenosine deaminase deficiency vector encoding Services (ADA-SCID) 05/2028 for the human Limited adenosine deaminase (ADA)) Zalmoxis (allogeneic T cells genetically modified with a retroviral vector encoding for a Adjunctive treatment in haematopoietic truncated form stem cell transplantation (HSCT) of 156 129 of the human MolMed SpA adult patients with high-risk low affinity haematological malignancies 08/2026 nerve growth factor receptor and the herpes simplex I virus thymidine kinase) Metastatic adenocarcinoma of the Onivivyde pancreas, in combination with 5 Baxalta (irinotecan fluorouracil (5 FU) and leucovorin (LV), 157 130 Innovations hydrochloride in adult patients who have progressed GmbH trihydrate) following gemcitabine based therapy 10/2026 Lartruvo (olaratumab) Eli Lilly Treatment of adult patients advanced 158 131 WITHDRAWN Nederland soft tissue sarcoma 11/2026 FROM THE B.V. MARKET NINLARO in combination with lenalidomide and dexamethasone is Ninlaro Takeda indicated for the treatment of adult 159 132 (ixazomib) Pharma A/S patients with multiple myeloma who have received at least one prior therapy 11/2026 Venclyxto 160 133 (venetoclax) AbbVie Ltd Chronic lymphocytic leukemia WITHDRAWN 16

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Ocaliva Intercept Primary biliary cholangitis in adults 161 134 (obeticholic Pharma Ltd 12/2026 acid) Advanced SomaKit TOC Diagnosis of gastro-entero-pancreatic 162 135 Accelerator neuroendocrine tumours 12/2026 (edotreotide) Applications 2017

Cystadrops Orphan Treatment of corneal cystine crystal 163 136 (mercaptamine) Europe deposits in adults and children from 2 S.A.R.L. years of age with cystinosis 01/2027 Ledaga is indicated for the topical Actelion treatment of mycosis fungoides-type 164 137 Ledaga Registration cutaneous T-cell lymphoma (MF type (chlormethine) Ltd CTCL) in adult patients 03/2027 Natpar is indicated as adjunctive Natpar Shire treatment of adult patients with chronic 165 138 (parathyroid Pharmaceutic hypoparathyroidism who cannot be hormone) als Ireland Ltd adequately controlled with standard therapy alone 04/2027 Qarziba (previously Dinutuximab EUSA Pharma Neuroblastoma (in patients over 1 year 166 139 beta EUSA and (Netherlands) of age) 11/2027 Dinutuximab B.V. beta Apeiron) (dinutuximab beta) Biogen Idec 167 140 Spinraza 5q Spinal muscular atrophy 06/2027 (nusinersen) Ltd Biomarin Brineura Neuronal ceroid lipofuscinosis type 2 168 141 International (cerliponase (CLN2) disease 06/2027 alfa) Limited Treatment of adults with Philadelphia Besponsa chromosome positive (Ph+) relapsed or 169 142 (inotuzumab Pfizer Limited refractory CD22-positive B cell ozogamicin) precursor acute lymphoblastic leukaemia (ALL) 03/2027 Oxervate Treatment of moderate (persistent Dompe (recombinant epithelial defect) or severe (corneal 170 143 farmaceutici human nerve ulcer) neurotrophic keratitis in adults s.p.a. growth factor - 10/2027 cenegermin) Bavencio is indicated as monotherapy Merck Serono for the treatment of adult patients with 171 144 Bavencio Europe (avelumab) metastatic Merkel cell carcinoma (MCC) Limited 09/2027

Novartis Rydapt® Adult patients with acute myeloid 172 145 Europharm (midostaurin) leukemia (AML) 09/2027 Ltd Adult patients with aggressive systemic Novartis mastocytosis (ASM), systemic Rydapt® 173 Europharm mastocytosis with associated (midostaurin) Ltd haematological neoplasm (SM AHN), or mast cell leukaemia (MCL) 09/2027 Treatment of carcinoid syndrome diarrhoea in combination with Xermelo® 174 146 somatostatin analogue (SSA) therapy in (telotristat Ipsen Pharma adults inadequately controlled by SSA etiprate) therapy 09/2027

175 147 Lutathera Advanced Lutathera is indicated for the treatment (lutetium Accelerator of unresectable or metastatic, 17

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(177Lu) Applications progressive, well differentiated (G1 and oxodotreotide) G2), somatostatin receptor positive gastroenteropancreatic neuroendocrine tumours (GEP NETs) in adults 09/2027 Zejula is indicated as monotherapy for the maintenance treatment of adult patients with platinum sensitive relapsed high grade serous epithelial ® 176 148 Zejula Tesaro UK ovarian, fallopian tube, or primary (niraparib) limited peritoneal cancer who are in response (complete or partial) to platinum based chemotherapy 11/2027

Treatment of inborn errors of primary Chenodeoxych bile acid synthesis due to sterol 27 hydroxylase deficiency (presenting as olic acid Leadiant 177 149 cerebrotendinous xanthomatosis (CTX)) Leadiant GmbH (chenodeoxycho in infants, children and adolescents lic acid) aged 1 month to 18 years and adults 12/2027 2018

Jorveza® Dr. Falk Eosinophilic esophagitis (EoE) in adults 178 150 (budesonide) Pharma GmbH 1/2028

Prevymis® Merck Sharp Prophylaxis of cytomegalovirus (CMV) (letermovir) & Dohme reactivation and disease in adult CMV- 179 151 Limited seropositive recipients [R+] of an allogeneic haematopoietic stem cell transplant (HSCT) 1/2028 Kyowa Kirin X-linked hypophosphataemia (to be Crysvita® 180 152 Limited used in children over 1 year of age and (burosumab) adolescents) 3/2028

Lamzede® Chiesi Enzyme replacement therapy for the (velmanase Farmaceutici treatment of non-neurological 181 153 alfa) S.p.A. manifestations in patients with mild to moderate alpha-mannosidosis (to be used in children aged 6 years and older, and adults) 3/2028 Alofisel® Tigenix, S.A.U. Complex perianal fistulas in adults with 182 154 (darvadstrocel) Crohn’s disease 4/2028

Mylotarg® Pfizer Limited Indicated for combination therapy with (gemtuzumab daunorubicin (DNR) and cytarabine ozogamicin) (AraC) for the treatment of patients age 183 155 15 years and above with previously untreated, de novo CD33 positive acute myeloid leukaemia (AML), except acute promyelocytic leukaemia (APL) 4/2028 Amglidia® Ammtek Neonatal diabetes mellitus (newborns, 184 156 (glibenclamide) infants and children) 5/2028

Rubraca® Clovis High-grade cancers of the ovary, (rucaparib) Oncology UK fallopian tubes and peritoneum. Limited WITHDRAWN New indication 2018_ maintenance treatment of adult patients with 185 157 and waiting 2018? for EC platinum-sensitive relapsed high-grade decision for a epithelial ovarian, fallopian tube, or new indication primary peritoneal cancer who are in response (complete or partial) to platinum-based chemotherapy Santen Oy Treatment of severe vernal Verkazia® 186 158 keratoconjunctivitis (VKC) in children (ciclosporin) from 4 years of age and adolescents

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7/2030

Tegsedi® Akcea Treatment of stage 1 or stage 2 187 159 (inotersen Therapeutics polyneuropathy in adult patients with sodium) Ireland Ltd hereditary transthyretin amyloidosis (hATTR) 07/2028 Aegerion Myalepta is indicated as an adjunct to Pharmaceutic diet as a replacement therapy to treat als B.V. the complications of leptin deficiency in lipodystrophy (LD) patients with or Myalepta® acquired partial LD (Barraquer-Simons 188 160 () syndrome), in adults and children 12 years of age and above for whom standard treatments have failed to achieve adequate metabolic control 08/2028

Aegerion Myalepta is indicated as an adjunct to Pharmaceutic diet as a replacement therapy to treat Myalepta® als B.V. the complications of leptin deficiency in 189 (metreleptin) lipodystrophy (LD) patients with confirmed congenital generalised LD (Berardinelli-Seip syndrome) 08/2028

Aegerion Myalepta is indicated as an adjunct to Pharmaceutic diet as a replacement therapy to treat als B.V. the complications of leptin deficiency in Myalepta® 190 lipodystrophy (LD) patients with or (metreleptin) acquired generalised LD (Lawrence syndrome) in adults and children 2 years of age and above 08/2028

Aegerion Myalepta is indicated as an adjunct to Pharmaceutic diet as a replacement therapy to treat Myalepta® 191 als B.V. the complications of leptin deficiency in (metreleptin) lipodystrophy (LD) patients with confirmed familial partial LD 08/2028

Vyxeos® Jazz Adults with newly diagnosed, t herapy- Pharmaceutic related acute myeloid leukaemia (t-AML) 192 161 (daunorubicin / cytarabine) als Ireland or AML with myelodysplasia-related Limited changes (AML-MRC) 08/2028 Mepsevii® Ultragenyx Non-neurological manifestations (vestronidase Germany Mucopolysaccharidosis type VII (MPS 193 162 alfametreleptin) GmbH VII, also known as Sly syndrome) 08/2028 Kymriah® Novartis Kymriah is indicated for the treatment Europharm of paediatric and young adult patients 194 163 (tisagenlecleuce Limited up to 25 years of age with B-cell acute l) lymphoblastic leukaemia (ALL) 8/2028

Kymriah® Novartis Adult patients with relapsed or Europharm refractory diffuse large B cell lymphoma 195 (tisagenlecleuce Limited (DLBCL) 08/2028 l)

Yescarta® Kite Pharma Treatment of adult primary mediastinal EU B.V. large B-cell lymphoma (PMBCL), after 196 164 (axicabtagene two or more lines of systemic ciloleucel) therapy.lymphoma (PMBCL) 08/2028

Yescarta® Kite Pharma Treatment of adult patients with EU B.V. relapsed or refractory diffuse large B- 197 (axicabtagene cell lymphoma (DLBCL) 08/2028 ciloleucel)

Alnylam Hereditary transthyretin-mediated 198 165 Onpattro® Netherlands amyloidosis (hATTR) in adult patients 19

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(patisiran) B.V. with stage 1 or stage 2 polyneuropathy 08/2028

Ablynx NV Adults experiencing an episode of acquired thrombotic thrombocytopenic Cablivi® 166 purpura (aTTP), in conjunction with 199 (caplacizumab) plasma exchange and immunosuppression 09/2028

Vertex Cystic fibrosis in patients aged 12 years Symkevi® Pharmaceutic and above 11/2028 200 167 (patisiran) als (Europe) Ltd

Shire Indicated for routine prevention of Takhzyro Pharmaceutic recurrent attacks of hereditary 201 168 (lanadelumab) als Ireland angioedema (HAE) in patients aged 12 Limited years and older 11/2028

Kyowa Kirin Treatment of adult patients with Poteligeo Holdings B.V. mycosis fungoides (MF) or Sézary 202 169 (Mogamulizum syndrome (SS) who have received at ab) least one prior systemic therapy 11/2028

Luxturna® Spark Adults and children with loss of vision Therapeutics due to inherited retinal dystrophies 1) (voretigene 203 170 Ireland Ltd Leber’s congenital amaurosis 2) retinitis neparvovec) pigmentosa 12/2028

Namuscla® Lupin Europe Symptomatic treatment of myotonia in 204 171 GmbH adult patients with non-dystrophic (mexiletine hcl) myotonic disorders 12/2028

2019

Palynziq® BioMarin Phenylketonuria (PKU) () International 205 172 Limited

Akcea Familial chylomicronaemia syndrome Waylivra® Therapeutics (FCS) 206 173 (volanesorsen) Ireland Limited

Zynteglo® bluebird bio beta-Thalassemia (Autologous (Netherlands) CD34+ cells B.V. 207 174 encoding βA- T87Q-globin gene) Epidyolex® GW Pharma Lennox-Gastaut and Dravet syndromes (Cannabidiol) (International) 208 175 B.V.

Astellas Acute myeloid leukaemia (AML) Xospata® 209 176 Pharma (gilteritinib) Europe B.V.

2020

Isturisa® Novartis Cushing Syndrome 210 177 (osilodrostat) Europharm Limited

Roche 211 178 Diffuse large B-cell lymphoma (DLBCL) Polivy® Registration 20

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(polatuzumab GmbH vedotin)

Alnylam 212 179 Givlaari® Netherlands B.V. Acute hepatic () Trepulmix® Chronic thromboembolic pulmonary 213 180 (Treprostinil) SciPharm Sàrl hypertension (CTEPH)

Zolgensma® 214 181 (onasemnogene AveXis EU abeparvovec) Limited Spinal muscular atrophy (SMA)

Reblozyl® Celgene Beta thalassaemia & Myelodysplastic 215 182 (luspatercept) Europe B.V. syndromes

Daurismo® Pfizer Europe Newly-diagnosed acute myeloid 216 183 (glasdegib) MA EEIG leukaemia (AML)

Pretomanid FGK FGK® 217 184 Representative (pretomanid) Service GmbH Adults with drug-resistant tuberculosis

Hepcludex® Chronic (long-term) hepatitis delta virus 218 185 (bulevirtide) MYR GmbH (HDV) infection in adults

Idefirix® Hansa Prevent the body from rejecting a newly 219 186 (imlifidase) Biopharma AB transplanted kidney

Kaftrio® Vertex (ivacaftor / Pharmaceutic 220 187 tezacaftor / als (Ireland) elexacaftor) Limited Cystic fibrosis

Blenrep® GlaxoSmithKli 221 188 (belantamab ne (Ireland) mafodotin) Limited Multiple Myeloma

Blueprint Medicines 189 Ayvakyt® 222 (Netherlands) (avapritinib) B.V. Gastrointestinal stromal tumour (GIST)

Arikayce liposomal® Insmed 190 223 (amikacin Netherlands Adults with a lung infection caused by sulfate) B.V. Mycobacterium avium complex (MAC)

Novartis Adakveo® 224 191 Europharm Sickle cell disease aged 16 years and (crizanlizumab) Limited older

Alnylam 225 192 Oxlumo® Netherlands () B.V. Primary hyperoxaluria type 1

SFL Pharmaceutic Obiltoxaximab 193 als 226 SFL ® Deutschland Inhalational anthrax due to Bacillus (obiltoxaximab) GmbH anthracis

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Libmeldy® (autologous Orchard 227 194 CD34+ cells Therapeutics encoding ARSA (Netherlands) gene) BV Metachromatic leukodystrophy (MLD)

Fintepla®

228 195 (fenfluramine) Zogenix ROI Seizures associated with Dravet Limited syndrome

Tecartus® (Autologous peripheral blood T cells CD4 and CD8 selected and CD3 and CD28 activated transduced 229 196 with retroviral vector expressing anti-CD19 CD28/CD3- zeta chimeric antigen receptor and Adults with mantle cell lymphoma (a cultured) Kite Pharma cancer of B cells, a type of white blood EU B.V. cell)

2021

Stemline 230 197 Elzonris® Therapeutics Adults with blastic plasmacytoid (tagraxofusp) B.V. dendritic cell neoplasm (BPDCN) a = Number of positive CHMP opinions; b =Number of different products c = International Non-proprietary Name (INN) EXPIRED product reached the end of the period of market exclusivity WITHDRAWN: withdrawn from the Community Register of orphan medicinal products upon request of the marketing authorisation holder WITHDRAWN FROM THE MARKET – SAFETY withdrawn from the market in the European Union due to safety reasons XX/XXXX Date that the market exclusivity will end

This publication (or activity) has been funded with support from the European Union's Health Programme. This material only reflects the views of the author, and funders cannot be held responsible for any use which may be made of the information contained herein.

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