Orphan Medicinal Products with Marketing Authorisation

Orphan medicinal products with marketing authorisation

(http://ec.europa.eu/health/documents/community-register/html/orphreg.htm)

List of Orphan Medicinal Products with Marketing Authorisation (as of May 2016) N° CHMP + N° Medicinal Product MA Sponsor Authorised Therapeutic Indication opinions productsb a

2001

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

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

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adult patients with Kit (CD 117) positive 4 (imatinib) 2002 Europharm Limited unresectable and/or metastatic malignant WITHDRAWN gastrointestinal stromal tumours (GIST).

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Novartis Treatment of adult patients with 5 (imatinib) unresectable recurrent and/or metastatic 2006 Europharm Limited WITHDRAWN dermafibrosarcoma protuberans

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Philadelphia chromosome positive 6 (imatinib) 2006 Europharm Limited acute lymphoblastic leukaemia (Ph+ ALL) as WITHDRAWN monotherapy

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myeloproliferative diseases 7 (imatinib) 2006 Europharm Limited (MDS/MPD) associated with PDGFR gene re- WITHDRAWN arrangement

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Novartis Treatment of adult patients with 8 (imatinib) hypereosinophilic syndrome (HES) and 2006 Europharm Limited WITHDRAWN chronic eosinophilic leukaemia (CEL)

2002

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

N° CHMP + N° Medicinal Product MA Sponsor Authorised Therapeutic Indication opinions productsb a

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 EXPIRED Limited significant interstitial pulmonary disease. - 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 (miglustat) 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 Limited paediatric patients with Niemann-Pick type C disease.

2003

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

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

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

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

N° CHMP + N° Medicinal Product MA Sponsor Authorised Therapeutic Indication opinions productsb a

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

2004

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

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

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

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

Wilzin (zinc-acetate Orphan Europe 25 17 Treatment of Wilson's disease dihydrate) 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 Pharmaceuticals hydrochloride) whose elevated platelet counts are not Ltd EXPIRED reduced to an acceptable level by their current therapy.

2005

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

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

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

Revatio Treatment of pulmonary arterial 30 22 Pfizer limited hypertension. Revatio has been shown to (sidenafil citrate) improve exercise ability and to reduce mean 3

N° CHMP + N° Medicinal Product MA Sponsor Authorised Therapeutic Indication opinions productsb a EXPIRED pulmonary arterial pressure

2006

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

Myozyme is indicated for long-term enzyme replacement therapy (ERT) in patients with a Myozyme confirmed diagnosis of Pompe disease (acid (recombinant alpha-glucosidase deficiency). 32 24 human acid alpha- Genzyme 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 relapsed or are refractory after receiving at Evoltra Genzyme Europe 33 25 least two prior regimens and where there is (clofarabine) BV no other treatment option anticipated to result in a durable response. Safety and efficacy have been assessed in studies of patients ≤ 21 years old at initial diagnosis.

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

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

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

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

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

Treatment of adults with Philadelphia chromosome positive (Ph+) acute lymphoblastic leukaemia (ALL) and lymphoid blast CML with resistance or intolerance to Sprycel Bristol-Myers 39 29 prior therapy. (dasatinib) Squibb 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 Sutent is indicated for the treatment of 40 30 (sunitinib) Pfizer Ltd. advanced and/or metastatic renal cell WITHDRAWN carcinoma.

N° CHMP + N° Medicinal Product MA Sponsor Authorised Therapeutic Indication opinions productsb a

Sutent is indicated for the treatment of unresectable and/or metastatic malignant gastrointestinal stromal tumour (GIST) after failure of imatinib mesylate treatment due to resistance or intolerance.

Treatment of patients with pulmonary Thelin arterial hypertension classified as WHO (sitaxentan 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 - SAFETY connective tissue disease.

2007

Indicated for use in conjunction with clobazam and valproate as adjunctive Diacomit therapy of refractory generalized tonic-clonic 42 32 BIOCODEX seizures in patients with severe myoclonic (stiripentol) 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 43 33 (iduronate-2- Genetic Therapies (Mucopolysaccharidosis II, MPS II). sulfatase) AB - Sweden Heterozygous females were not studied in the clinical trials."

Inovelon Adjunctive therapy in the treatment of 44 34 Esai Limited seizures associated with Lennox-Gastaut (rufinamide) 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), 45 35 (betaine anhydrous Ophan Europe - cobalamin cofactor metabolism (cbl). A) 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 transplant. 46 36 Celgene Europe Ltd (lenalidomide) Revlimid in combination with dexamethasone is indicated for the treatment of multiple myeloma in adult patients who have received at least one prior therapy.

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

Indicated in adults and children for the treatment of patients with paroxysmal Soliris 48 37 Alexion Europe nocturnal haemoglobinuria (PNH). Evidence (eculizumab) of clinical benefit demonstrated in patients with haemolysis with clinical symptom(s) indicative of high disease activity, regardless

N° CHMP + N° Medicinal Product MA Sponsor Authorised Therapeutic Indication opinions productsb a

of transfusion history

Soliris Alexion Europe SAS Extension Of Indication for atypical 49 2011 (eculizumab) - France haemolytic uremic syndrome (aHUS)

"Indicated for the prevention of recurrent Siklos Addmedica SAS - painful vaso-occlusive crises including acute 50 38 chest syndrome in adults, adolescents and (hydroxyurea) France 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, 51 39 Ipsen Pharma hypothyroidism, or chronic treatment with (mecasermin) 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 disease has not responded to or has relapsed Atriance 52 40 Glaxo Group Ltd following treatment with at least two nelarabine) chemotherapy regimens. Due to the small patient populations in these disease settings, the information to support these indications is based on limited data.

Gliolan (5 aminolevulinic Visualisation of malignant tissue during 53 41 Medac GmbH acid hydrochloride surgery for malignant glioma L)

Treatment of patients with advanced soft tissue sarcoma, after failure of Yondelis anthracyclines and ifosfamide, or who are 54 42 PharmaMar SA (trabectedin) unsuited to receive these agents. Efficacy 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 anthracyclines and ifosfamide, or who are Yondelis unsuited to receive these agents. Efficacy 55 PharmaMar SA 2009 (trabectedin) data are based mainly on liposarcoma and leiomyosarcoma patients. In combination with pegylated liposomal doxorubicin (PLD) is indicated for the treatment of patients with relapsed platinum-sensitive ovarian cancer.

N° CHMP + N° Medicinal Product MA Sponsor Authorised Therapeutic Indication opinions productsb a

Torisel First-line treatment of patients with 56 43 Pfizer Limited advanced renal cell carcinoma who have at (temsirolimus) least three of six prognostic risk factors.

Torisel EXTENSION OF INDICATION to include 57 Pfizer Limited treatment of adult patients with relapsed 2009 (temsiroliums) and/or refractory mantle cell lymphoma.

Tasigna Novartis Treatment of Philadelphia chromosome 58 44 positive chronic myelogenous leukaemia (nilotinib) Europharm Ltd (CML)

2008

Thalidomide Celgene in combination with Thalidomide Celgene Europe melphalan and prednisone as first line 59 45 Celgene treatment of patients with untreated multiple Limited (thalidomide) myeloma, aged ≥ 65 years or ineligible for high dose chemotherapy.

Treatment of patients with pulmonary Volibris arterial hypertension (PAH) classified as 60 46 Glaxo Group Ltd (ambrisentan) WHO functional class II and III, to improve exercise capacity.

Firazyr Shire Orphan Indicated for symptomatic treatment of acute 61 47 attacks of hereditary angioedema (HAE) in (icatibant acetate L) Therapies GmbH adults (with C1-esterase-inhibitor deficiency).

Ceplene maintenance therapy is indicated for Ceplene adult patients with acute myeloid leukaemia in first remission concomitantly treated with 62 48 (histamine Meda AB interleukin-2 (IL-2). The efficacy of Ceplene dihydrochloride) has not been fully demonstrated in patients older than age 60.

Treatment of hyperphenylalaninaemia (HPA) in adult and paediatric patients of 4 years of age and over with phenylketonuria (PKU) Kuvan who have been shown to be responsive to Merck Serono such treatment. Kuvan is also indicated for 63 49 (sapropterin Europe Limited the treatment of hyperphenylalaninaemia dihydrochloride) (HPA) in adult and paediatric patients with tetrahydrobiopterin (BH4) deficiency who have been shown to be responsive to such treatment.

Treatment of adult patients who are not eligible for haematopoietic stem cell transplantation with:  intermediate-2 and high-risk myelodysplastic syndromes (MDS) Celgene Europe according to the International Prognostic Vidaza 64 50 Ltd- United Scoring System (IPSS), (azacitidine) Kingdom  chronic myelomonocytic leukaemia (CMML) with 10-29% marrow blasts 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 65 51 Amgen Europe BV (romiplostim) treatments (e.g. corticosteroids, immunoglobulins). Nplate may be considered as second line treatment for adult non- splenectomised patients where surgery is

N° CHMP + N° Medicinal Product MA Sponsor Authorised Therapeutic Indication opinions productsb a

contra-indicated.

Indicated in children, adolescents and young adults for the treatment of high-grade Mepact 66 52 Takeda France SAS resectable non-metastatic osteosarcoma after (mifamurtide) macroscopically complete surgical resection. It is used in combination with post-operative multi-agent chemotherapy.

Peyona Chiesi Farmaceutici Treatment of primary apnoea of premature 67 53 (previously Nymusa, S.P.A. - Italy newborns. caffeine citrate

Indicated in combination with G-CSF to enhance mobilisation of haematopoietic stem Mozobil Genzyme BV The cells to the peripheral blood for collection 68 54 (plerixafor) Netherlands and subsequent autologous transplantation in patients with lymphoma and multiple myeloma whose cells mobilise poorly.

Cayston Gilead Sciences Suppressive therapy of chronic pulmonary infections due to Pseudomonas aeruginosa in 69 55 (aztreonam lysinate International Ltd – patients with cystic fibrosis (CF) aged 18 inhalation use) UK years and older.

Rilonacept Regeneron Treatment of Cryopyrin-Associated Periodic (formerly Arcalyst; Syndromes (CAPS) including Familial Cold 70 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 Europe Symptomatic treatment of Lambert-Eaton 71 57 (amifampridine) Ltd myasthenic syndrome (LEMS) in adults.

Indicated for adult chronic immune (idiopathic) thrombocytopenic purpura (ITP) Revolade GlaxoSmithKline splenectomised patients who are refractory to other treatments (e.g. corticosteroids, 72 58 (eltrombopag) Trading Services immunoglobulins). Revolade may be WITHDRAWN Limited – Ireland considered as second line treatment for adult non-splenectomised patients where surgery is contraindicated.

Treatment of patients with advanced renal Afinitor Novartis 73 59 cell carcinoma, whose disease has (everolimus) Europharm Ltd progressed on or after treatment with VEGF- WITHDRAWN 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-Wells Syndrome (MWS), Neonatal-Onset Ilaris Novartis Multisystem Inflammatory Disease (NOMID) 74 60 (canakinumab) Europharm Ltd. / Chronic Infantile Neurological, Cutaneous, WITHDRAWN 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 Tepadina 75 61 Adienne S.r.l - Italy chemotherapy medicinal products: (thiotepa) 1) with or without total body irradiation (TBI), as conditioning treatment prior to 8

N° CHMP + N° Medicinal Product MA Sponsor Authorised Therapeutic Indication opinions productsb a

allogeneic or autologous haematopoietic progenitor cell transplantation (HPCT) in 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 (CLL): Arzerra Glaxo Group 76 62 (ofatumumab) Limited - UK Arzerra is indicated for the treatment of CLL in patients who are refractory to fludarabine and alemtuzumab.

Previously untreated chronic lymphocytic leukaemia (CLL): Arzerra Glaxo Group Arzerra in combination with chlorambucil or 77 2014 (ofatumumab) Limited - UK bendamustine is indicated for the treatment of patients with CLL who have not received prior therapy and who are not eligible for fludarabine-based therapy.

Shire VPRIV Pharmaceuticals 78 63 Treatment of type 1 Gaucher disease (velaglucerase alfa) Ireland Limited – Ireland

2011

Esbriet 79 64 InterMune UK Ltd. Treatment of idiopathic pulmonary fibrosis (perfenidone)

Suppressive therapy of chronic pulmonary Novartis 80 65 TOBI podhaler infection due to Pseudomonas aeruginosa in (tobramycin) Europharm Limited adults and children aged 6 years and older with cystic fibrosis

Treatment of patients aged 3 years and older Novartis with subependymal giant cell astrocytoma 81 66 Votubia (SEGA) associated with tuberous sclerosis (everolimus) Europharm Limited complex (TSC) who require therapeutic intervention but are not amenable to surgery

Plenadren (hydrocortisone 82 67 ViroPharma SPRL Treatment of adrenal insufficiency (modified release tablet)

Vyndaqel Treatment of transthyretin amyloidosis in 83 68 Pfizer Limited - UK (tafamidis) patients with symptomatic polyneuropathy

2012

Xaluprine (previously known Nova Laboratories 84 69 as Mercaptopurine Treatment of acute lymphoblastic leukaemia Limited - UK Nova Laboratories and Novapurine)

Bronchitol Pharmaxis 85 70 Treatment of cystic fibrosis (manitolum) Pharmaceuticals

Novartis Signifor Treatment of adult patients with Cushing’s 86 71 Europharm Limited disease for whom surgery is not an option or (pasireotide) UK for whom surgery has failed

N° CHMP + N° Medicinal Product MA Sponsor Authorised Therapeutic Indication opinions productsb a

Treatment of adult patients with acromegaly Novartis Signifor for whom surgery is not an option or has not 87 Europharm Limited been curative and who are inadequately 2014 (pasireotide) UK controlled on treatment with another somatostatin analogue.

Vertex Kalydeco Treatment of cystic fibrosis (CF) in patients 88 72 Pharmaceuticals age 6 years and older who have a G551D ivacaftor (U.K.) Limited mutation in the CFTR gene

Treatment of disease related splenomegaly or Novartis symptoms in adult patients with primary Jakavi myelofibrosis (also known as chronic 89 73 Europharm Limited (ruxolitinib) idiopathic myelofibrosis), post polycythaemia WITHDRAWN - UK vera myelofibrosis or post essential thrombocythaemia myelofibrosis.

Treatment of adult patients with Short Bowel NPS Pharma 90 74 Revestive Syndrome. Patients should be stable (teduglutide) Holdings Limited following a period of intestinal adaptation after surgery.

Long-term prophylactic treatment of bleeding NovoThirteen 91 75 Novo Nordisk A/S in adult and paediatric patients 6 years and (catridecacog) above with congenital factor-XIII-A-subunit WITHDRAWN deficiency.

Treatment of adult patients aged 65 years Janssen-Cilag and above with newly diagnosed de novo or Dacogen secondary acute myeloid leukaemia (AML), 92 76 International NV - (decitabine) according to the World Health Organisation Belgium (WHO) classification, who are not candidates for standard induction chemotherapy”.

Glybera is indicated for adult patients Glybera diagnosed with familial lipoprotein lipase (adeno-associated uniQure biopharma deficiency (LPLD) and suffering from severe or multiple pancreatitis attacks despite 93 77 viral vector B.V. - The dietary fat restrictions. The diagnosis of expressing Netherlands LPLD has to be confirmed by genetic testing. lipoprotein lipase The indication is restricted to patients with detectable levels of LPL protein

Adcetris is indicated for the treatment of adult patients with relapsed or refractory CD30+ H83 (Hodgkin’s lymphoma): Takeda Global 1.following autologous stem-cell transplant Adcetris Research and (ASCT) or; 94 78 (brentuximab Development 2.following at least two prior therapies when vedotin) Centre (Europe) Ltd ASCT or multi-agent chemotherapy is not a - UK treatment option. Adcetris is indicated for the treatment of adult patients with relapsed or refractory systemic anaplastic large cell lymphoma (sALCL). NexoBrid (concentrate of MediWound NexoBrid is indicated for removal of eschar 95 79 proteolytic enzymes in adults with deep partial- and full- Germany GmbH enriched in thickness thermal burns. bromelain)

2013

Bosulif Pfizer Limited 96 80 Treatment of chronic myeloid leukaemia (bosutinib) United Kingdom

Iclusig is indicated in adult patients with: Iclusig ARIAD Pharma Ltd 97 81 1) chronic-phase, accelerated-phase or blast- (ponatinib) - UK phase chronic myeloid leukaemia (CML) who are resistant to dasatinib or nilotinib, who 10

N° CHMP + N° Medicinal Product MA Sponsor Authorised Therapeutic Indication opinions productsb a

are intolerant to dasatinib or nilotinib and for whom subsequent treatment with imatinib is not clinically appropriate, or who have the T315I mutation; 2) Philadelphia-chromosome-positive acute lymphoblastic leukaemia (Ph+ ALL) who are resistant to dasatinib, who are intolerant to dasatinib and for whom subsequent treatment with imatinib is not clinically appropriate, or who have the T315I mutation.

Pomalidomide Celgene in combination with Imnovid dexamethasone is indicated in the treatment (previously of adult patients with relapsed and refractory Celgene Europe multiple myeloma who have received at least 98 82 Pomalidomide Limited - UK two prior treatment regimens, including both Celgene; lenalidomide and bortezomib, and have pomalidomide) demonstrated disease progression on the last therapy.

Probysbi is indicated for the treatment of Raptor proven nephropathic cystinosis. Cysteamine Procysbi Pharmaceuticals reduces cystine accumulation in some cells 99 83 (cysteamine (e.g. leukocytes, muscle and liver cells) of Europe BV - The bitartrate) nephropathic cystinosis patients and, when Netherlands treatment is started early, it delays the development of renal failure.

Orphacol is indicated for the treatment of inborn errors in primary bile-acid synthesis Orphacol due to 3β-hydroxy-Δ5-C27-steroid 100 84 Laboratoires CTRS oxidoreductase deficiency or Δ4-3-oxosteroid- (cholic acid) 5β-reductase deficiency in infants, children and adolescents aged one month to 18 years and adults

Defitelio is indicated for the treatment of Defitelio Gentium S.p.A. - severe hepatic veno-occlusive disease (VOD) 101 85 also known as sinusoidal obstructive (defibrotide) Italy syndrome (SOS) in haematopoietic stem-cell transplantation (HSCT) therapy.

Opsumit, as monotherapy or in combination, Opsumit Actelion is indicated for the long-term treatment of 102 86 pulmonary arterial hypertension (PAH) in (macitentan) Registration adult patients of WHO Functional Class (FC) II to III.

Jinarc Otsuka Autosomal dominant polycystic kidney 103 87 (tolvaptan) Pharmaceutical disease WITHDRAWN Europe Ltd

2014

Indicated for use as part of an appropriate Janssen-Cilag combination regimen for pulmonary Sirturo multidrug resistant tuberculosis (MDR TB) in 104 88 International N.V. (bedaquiline adult patients when an effective treatment fumarate) Belgium regimen cannot otherwise be composed for reasons of resistance or tolerability

Treatment of adult patients with progressive, 105 89 Cometriq TMC Pharma unresectable locally advanced or metastatic (cabozantinib) medullary thyroid carcinoma

Treatment of Chronic thromboembolic 106 90 Adempas Bayer Pharma AG pulmonary hypertension (CTEPH) and (riociguat) Pulmonary arterial hypertension (PAH)

N° CHMP + N° Medicinal Product MA Sponsor Authorised Therapeutic Indication opinions productsb a

Kolbam FGK Representative Inborn errors in primary bile-acid 107 91 (cholic acid) Service GmbH, synthesis WITHDRAWN Germany

Kolbam Retrophin Europe Inborn errors in primary bile-acid 2015 (cholic acid) Ltd synthesis

Granupas (previously para- Lucane Pharma SA 108 92 Treatment of tuberculosis aminosalicylic acid - France Lucane or PAS-GR)

Otsuka Novel Deltyba Treatment of multidrug-resistant 109 93 Products GmbH - (delamanid) tuberculosis (MDR-TB) Germany

Vimizim BioMarin Europe Treatment of mucopolysaccharidosis, type 110 94 IVA (Morquio A Syndrome, MPS IVA) in (elosulfase alfa) Ltd patients of all ages.

Treatment of adult patients with multicentric Janssen-Cilag Castleman’s disease (MCD who are human 111 95 Sylvant (siltuximab) International NV immunodeficiency virus (HIV) negative and human herpesvirus-8 (HHV-8) negative.

Gazyvaro in combination with chlorambucil is indicated for the treatment of adult Roche Registration patients with previously untreated chronic 112 96 Gazyvaro (obinutuzumab) Ltd lymphocytic leukaemia (CLL) and with comorbidities making them unsuitable for full-dose fludarabine based therapy

Translarna is indicated for the treatment of Duchenne muscular dystrophy resulting from a nonsense mutation in the dystrophin PTC Therapeutics gene, in ambulatory patients aged 5 years 113 97 Translarna 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.

Janssen-Cilag Imbruvica is indicated for the treatment of 114 98 Imbruvica adult patients with relapsed or refractory (ibrutinib) International NV mantle cell lymphoma (MCL).

Imbruvica is indicated for the treatment of adult patients with chronic lymphocytic Janssen-Cilag leukaemia (CLL) who have received at least 115 Imbruvica one prior therapy, or in first line in the (ibrutinib) International NV presence of 17p deletion or TP53 mutation in patients unsuitable for chemo immunotherapy.

Ketoconazole HRA is indicated for the Laboratoire HRA treatment of endogenous Cushing’s 116 99 Ketoconazole HRA (ketoconazole) Pharma syndrome in adults and adolescents above the age of 12 years.

Lynparza is indicated as monotherapy for the maintenance treatment of adult patients with platinum-sensitive relapsed BRCA-mutated (germline and/or somatic) high grade serous 117 100 Lynparza AstraZeneca AB (olaparib) epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in response (complete response or partial response) to platinum-based chemotherapy.

Cyramza In combination with paclitaxel is indicated 118 101 Eli Lilly Nederland (ramucirumab) for the treatment of adult patients with 12

N° CHMP + N° Medicinal Product MA Sponsor Authorised Therapeutic Indication opinions productsb a WITHDRAWN B.V. advanced gastric cancer or gastro- oesophageal junction adenocarcinoma with disease progression after prior platinum and 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.

Prevention of phototoxicity in adult patients 119 102 Scenesse Clinuvel UK Limited (afamelanotide) with erythropoietic protoporphyria (EPP).

2015

Boehringer Ofev is indicated in adults for the treatment 120 103 Ofev Ingelheim Pharma of Idiopathic Pulmonary Fibrosis (IPF). (nibtedanib) GmbH & Co. KG

Cerdelga is indicated for the long-term treatment of adult patients with Gaucher Genzyme Europe 121 104 Cerdelga disease type 1 (GD1), who are CYP2D6 poor (eliglustat) BV metabolisers (PMs), intermediate metabolisers (IMs) or extensive metabolisers (EMs).

Treatment of adult patients with moderate to severe limbal stem cell deficiency (defined by Holoclar the presence of superficial corneal (ex vivo expanded neovascularisation in at least two corneal Chiesi Farmaceutici quadrants, with central corneal involvement, 122 105 autologous human corneal epithelial S.p.A. and severely impaired visual acuity), cells containing unilateral or bilateral, due to physical or stem cells) chemical ocular burns. A minimum of 1-2 mm2 of undamaged limbus is required for biopsy.

Lenvima is indicated for the treatment of adult patients with progressive, locally 123 106 Lenvima Eisai Europe Ltd advanced or metastatic, differentiated (lenvatinib mesylate) (papillary/follicular/Hürthle cell) thyroid carcinoma (DTC), refractory to radioactive iodine (RAI).

Vanda Hetlioz is indicated for the treatment of Non- 124 107 Hetlioz Pharmaceuticals 24-Hour Sleep-Wake Disorder (Non-24) in (tasimelteon) Ltd totally blind adults.

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 achieved at least a partial response, followed 125 108 Unituxin Therapeutics (dinutuximab) by myeloablative therapy and autologous 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 126 109 Kanuma (sebelipase alfa) BioPharma Ltd with lysosomal acid lipase deficiency.

Farydak is indicated in combination with bortezomib and dexamethasone, for the Novartis 127 110 Farydak treatment of relapsed and/or refractory (panobinostat ) Europharm Ltd multiple myeloma in adults patients. who have received at least two prior regimens including bortezomib and an

N° CHMP + N° Medicinal Product MA Sponsor Authorised Therapeutic Indication opinions productsb a

immunomodulatory agent.

Strensiq is indicated for long-term enzyme 128 111 Strensiq Alexion Europe SAS replacement therapy in patients with (asfotase alfa) paediatric-onset hypophosphatasia to treat the bone manifestations of the disease.

Santera Raxone is indicated for the treatment of visual impairment in adolescent and adult 129 112 Raxone Pharmaceuticals (ibedenone) patients with Leber’s Hereditary Optic Gmbh Neuropathy.

Cresemba is indicated for the treatment of 130 113 Cresemba Basilea Medical Ltd adults with invasive aspergillosis and (isavuconazole) mucormycosis in patients for whom amphotericin B is inappropriate.

Kyprolis is indicated for the treatment of 131 114 Kyprolis Amgen Europe BV (carfilzomib) multiple myeloma Orkambi Vertex Orkambi is indicated for the treatment of 132 115 (lumacaftor/ ivacaftor) Pharmaceuticals cystic fibrosis WITHDRAWN Obizur Baxalta Innovations Obizur is indicated for the treatment of 133 116 (susoctog alfa) GmbH haemophilia A WITHDRAWN Elocta Elocta is indicated for the treatment of 134 117 Biogen Idec Ltd (efmoroctocog alfa) haemophilia A WITHDRAWN Blincyto is indicated for the treatment of 135 118 Blincyto Amgen Europe B.V. precursor cell lymphoblastic leukemia- (blinatumomab) lymphoma

Horizon Ravicti Ravicti is indicated for the treatment of 136 119 Therapeutics (glycerol inborn urea cycle disorders phenylbutyrate) Limited Quinsair 137 120 (levofloxacin) Regintel Cystic fibrosis WITHDRAWN 2016

Coagadex Bio Products 138 121 Factor X deficiency (human coagulation Laboratory limited factor X) 139 122 Wakix Bioprojet Pharma Narcolepsy (pitolisant) Idelvion 140 123 (albutrepenonacog CSL Behring GmbH Haemophilia B alfa) Actelion 141 124 Uptravi Pulmonary arterial hypertension (selexipag) Registration Ltd

142 125 Alprolix Biogen Idec Ltd Haemophilia B (eftrenacog alfa) Janssen-Cilag 143 126 Darzalex Multiple myeloma (daratumumab) International N.V. Galafold Amicus 144 127 (migalastat Therapeutics UK Fabry disease hydrochloride) Ltd Strimvelis (autologous CD34+ GlaxoSmithKline Severe combined immunodeficiency due 145 128 + cells transduced Trading Services to adenosine deaminase deficiency with retroviral vector Limited (ADA-SCID) encoding for the 14

N° CHMP + N° Medicinal Product MA Sponsor Authorised Therapeutic Indication opinions productsb a human adenosine deaminase (ADA)) 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 upon request of the marketing authorisation holder from the Community Register of orphan medicinal products WITHDRAWN FROM THE MARKET – SAFETY withdrawn from the market in the European Union due to safety reasons

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.