European Coverage: Perfomance Tracker

Perfomance Tracker

ARTICLE PACK European CHMP Opinions and MAA Updates

Executive Summary legally binding decision, usually within 67 days. This is an update of recommendations from The CHMP at its monthly plenary meetings also the European Medicines Agency’s Committee assesses requests for modifications or extensions for Medicinal Products for Human Use on to existing marketing authorizations. the authorization of new medicines in the European Union, and updates on EU marketing The table below provides an overview of decisions authorization changes recommended by the on new marketing applications, applications CHMP. to extend the indication of existing marketing authorizations and requests for the re- examination of negative opinions the CHMP has adopted. It also covers the withdrawal of MAAs by The European Medicines Agency’s key scientific companies. panel, the Committee for Medicinal Products for Human Use (CHMP), meets once a month and The table has now been updated with products among other things adopts positive or negative that the CHMP discussed at its meeting in opinions on marketing authorization applications February 2020. (MAAs) filed through the centralized procedure for new molecular entities (NMEs), biosimilars and Please note: generic medicines. CHMP opinions are sent to Data in the following table is a sample only. the European Commission, which makes a final,

Brand and Generic Announce- Company Indication Recommendation/ Update Name ment Date Application withdrawn by company. BMS said it withdrew its application Extension of indication to include based on the fact that the Opdivo/Yervoy the use of Opdivo and Yervoy in Bristol-Myers EMA could not conclude that (nivolumab/ the treatment of metastatic non- Feb-20 Squibb there was a positive benefit- ipilimumab) small cell lung cancer that has not risk balance for the medicines been treated previously in the treatment of non-small cell lung cancer that has not been treated previously Application withdrawn by company. Blue Earth said it withdrew its application Extension of indication to include because the EMA considered Blue Earth Axumin (fluciclovine use in the diagnosis of glioma and Feb-20 that the data provided did Diagnostics (18F)) the continuing assessment of the not allow it to determine disease that the medicine’s benefit outweighs its risk when used for detecting glioma

2 / April 2020 © Informa UK Ltd 2020 (Unauthorized photocopying prohibited.) Extension of indication to include prevention of attacks in adults who suffer from episodic cluster Emgality Eli Lilly headache. For this use, Emgality Feb-20 Negative opinion, extension (galcanezumab) was to be available as a pre-filled syringe containing 100mg of the medicine. Addition of a new pharmaceutical form: a 108mg solution for injection to be given subcutaneously. The new Entyvio Takeda formulation is to be used as Feb-20 Positive opinion, extension (vedolizumab) maintenance treatment for all the authorized indications of Entyvio - ie Crohn’s disease and ulcerative colitis Extension of indication to include use as a treatment of adult patients with oral ulcers Amgen Otezla (apremilast) Feb-20 Positive opinion, extension associated with Behçet’s disease who are candidates for systemic therapy Extension of indication to include Boehringer use as a treatment of systemic Ofev (nintedanib) Feb-20 Positive opinion, extension Ingelheim sclerosis associated interstitial lung disease in adults Extension of indication to include use as monotherapy for the treatment of adult patients with anaplastic lymphoma kinase Takeda Alunbrig (brigatinib) Feb-20 Positive opinion, extension (ALK)-positive advanced non small cell lung cancer that has not previously been treated with an ALK inhibitor. Treatment of complicated skin Tigecycline Accord and soft tissue infections and Accord Healthcare Feb-20 Positive opinion (tigecycline) complicated intra-abdominal infections Treatment of infections due to Fetcroja aerobic Gram-negative organisms Shionogi Feb-20 Positive opinion (cefiderocol) in adults with limited treatment options Application withdrawn by the company. Merck said it decided to withdraw the Merck Sharp & Keytruda Treatment of cancer of the application because the Jan-20 Dohme (pembrolizumab) oesophagus results of the study were not considered sufficient to support an extension of indication at this time Application withdrawn by company. Celgene said it Treatment of adults with acute decided to withdraw the Celgene Idhifa (enasidenib) Jan-20 myeloid leukemia application because it could not fully address the major objections raised by the EMA

3 / April 2020 © Informa UK Ltd 2020 (Unauthorized photocopying prohibited.) Extension of indication for use in combination with obinutuzumab Venclyxto AbbVie for the treatment of adult patients Jan-20 Positive opinion, extension (venetoclax) with previously untreated chronic lymphocytic leukemia Extension of indication to expand use of Tybost from use in adults with HIV to use in adolescents aged 12 years and Gilead Sciences Tybost (cobicistat) Jan-20 Positive opinion, extension older – weighing at least 35kg co administered with atazanavir, or weighing at least 40kg co administered with darunavir The indication for Suliqua has been changed. It now reads that the product is indicated for the treatment of adults with Suliqua (insulin insufficiently controlled type 2 Sanofi glargine/ diabetes mellitus to improve Jan-20 Positive opinion, extension lixisenatide) glycemic control as an adjunct to diet and exercise in addition to metformin with or without sodium-glucose co-transporter-2 (SGLT-2) inhibitors Extension of indication to expand use of Rezolsta, in combination with other antiretroviral products, Rezolsta (darunavir/ Janssen-Cilag for use in the treatment of HIV in Jan-20 Positive opinion, extension cobicistat) adults to use in adolescents (aged 12 years and older, weighing at least 40kg) Two new extensions of indication: MabThera, in combination with glucocorticoids, is indicated for the induction of remission in pediatric patients (aged ≥2 to <18 years old) with severe, active granulomatosis with polyangiitis (Wegener’s) and microscopic polyangiitis; and MabThera, in MabThera combination in combination Roche Jan-20 Positive opinion, extension (rituximab) with chemotherapy is indicated for the treatment of pediatric patients (aged ≥6 months to <18 years old) with previously untreated advanced stage CD20 positive diffuse large B-cell lymphoma, Burkitt lymphoma/ Burkitt leukemia (mature B-cell acute leukemia) or Burkitt-like lymphoma Indication when used to treat Ameluz Biofrontera mild to moderate actinic (5-aminolevulinic Jan-20 Positive opinion, extension Bioscience keratoses extended to use on the acid) extremities and trunk/neck

4 / April 2020 © Informa UK Ltd 2020 (Unauthorized photocopying prohibited.) Trepulmix Treatment of chronic SciPharm (treprostinil thromboembolic pulmonary Jan-20 Positive opinion sodium) hypertension Budesonide/ Formoterol Teva Teva Pharma Treatment of asthma and chronic Jan-20 Positive opinion Pharmaceutical (budesonide/ obstructive pulmonary disease formoterol fumarate dihydrate) Treatment of secondary Cinacalcet hyperparathyroidism, parathyroid Accord Healthcare Accordpharma Jan-20 Positive opinion carcinoma and primary (cinacalcet) hyperparathyroidism Treatment of myelodysplastic Azacitidine Mylan syndromes, chronic Mylan Jan-20 Positive opinion (azacitidine) myelomonocytic leukemia and acute myeloid leukemia Treatment of myelodysplastic Azacitidine betapharm syndromes, chronic betapharm Jan-20 Positive opinion Arzneimittel myelomonocytic leukemia and (azacitidine) acute myeloid leukemia Arsenic trioxide Treatment of acute promyelocytic Mylan Mylan (arsenic Jan-20 Positive opinion leukemia trioxide) Treatment of non-Hodgkin’s lymphoma, chronic lymphocytic Ruxience leukemia, rheumatoid arthritis, Pfizer Jan-20 Positive opinion (rituximab) granulomatosis with polyangiitis and microscopic polyangiitis, and pemphigus vulgaris Staquis Pfizer Treatment of atopic dermatitis Jan-20 Positive opinion (crisaborole) Treatment of men with non- metastatic castration-resistant Nubeqa Bayer prostate cancer (nmCRPC) who Jan-20 Positive opinion (darolutamide) are at high risk of developing metastatic disease Nustendi Treatment of primary Esperion (bempedoic acid/ hypercholesterolemia and mixed Jan-20 Positive opinion Therapeutics ezetimibe) dyslipidemia Treatment of adults with Esperion Nilemdo primary hypercholesterolemia Jan-20 Positive opinion Therapeutics (bempedoic acid) (heterozygous familial and non- familial) or mixed dyslipidemia Liumjev (insulin Treatment of diabetes mellitus in Eli Lilly Jan-20 Positive opinion lispro) adults Vaxchora Emergent (Cholera vaccine For prophylaxis against cholera Jan-20 Positive opinion BioSolutions (recombinant, live, oral))

5 / April 2020 © Informa UK Ltd 2020 (Unauthorized photocopying prohibited.) Treatment of adults with insufficiently controlled type 2 Rybelsus Novo Nordisk diabetes to improve glycemic Jan-20 Positive opinion (semaglutide) control as an adjunct to diet and exercise Treatment for acute hepatic Alnylam porphyria in adults and Givlaari (givosiran) Jan-20 Positive opinion Pharmaceuticals adolescents aged 12 years and older Extension of indication to include a new presentation of Vyndaqel 61mg soft capsules Vyndaqel Pfizer for the treatment of wild-type Dec-19 Positive opinion, extension (tafamidis) or hereditary transthyretin amyloidosis in adult patients with cardiomyopathy (ATTR-CM) Extension of indication for use in younger patients when used to treat pediatric plaque psoriasis. The new wording now says Stelera is indicated for the Stelara treatment of moderate to severe Janssen-Cilag Dec-19 Positive opinion, extension (ustekinumab) plaque psoriasis in children and adolescent patients from the age of 6 years and older, who are inadequately controlled by, or are intolerant to, other systemic therapies or phototherapies Extension of indication to use in adolescents. The new wording now says Sirturo is indicated for use as part of an appropriate combination regimen for pulmonary multidrug-resistant Sirturo tuberculosis in adults and Janssen-Cilag Dec-19 Positive opinion, extension (bedaquiline) adolescent patients (12 years to less than 18 years of age and weighing at least 30kg) when an effective treatment regimen cannot otherwise be composed for reasons of resistance or tolerability Extension of indication to use in adult men for the treatment of Erleada metastatic hormone-sensitive Janssen-Cilag Dec-19 Positive opinion, extension (apalutamide) prostate cancer in combination with androgen deprivation therapy

6 / April 2020 © Informa UK Ltd 2020 (Unauthorized photocopying prohibited.) Extension of indication for the film-coated tablets. Dificlir film- coated tablets are still indicated in adults but the wording now says they are indicated for the treatment of Clostridioides Astellas Pharma Dificlir (fidaxomicin) Dec-19 Positive opinion, extension difficile infections (CDI) also known as C. difficile-associated diarrhea (CDAD) and that they can also be used to treat pediatric patients with a body weight of at least 12.5kg Extension of indication for use of Darzalex in combination with bortezomib, thalidomide and Darzalex dexamethasone for the treatment Janssen-Cilag Dec-19 Positive opinion, extension (daratumumab) of adult patients with newly diagnosed multiple myeloma who are eligible for autologous stem cell transplant Extension of indication for the use of Cyramza in combination with erlotinib for the first-line Cyramza treatment of adult patients with Eli Lilly Dec-19 Positive opinion, extension (ramucirumab) metastatic non-small cell lung cancer with activating epidermal growth factor receptor (EGFR) mutations A new pharmaceutical form associated with a new Akynzeo strength and a new route of Helsinn Birex (fosnetupitant/ administration as follows: Dec-19 Positive opinion, extension Pharmaceuticals palonosetron) Akynzeo 235mg/0.25mg powder for concentrate for solution for infusion for intravenous use Dexmedetomidine For the induction of light to Accord Healthcare Accord moderate sedation of adults in an Dec-19 Positive opinion (dexmedetomidine) intensive care unit Treatment of myelodysplastic Azacitidine Accord syndromes, chronic Accord Healthcare Dec-19 Positive opinion (azacitidine) myelomonocytic leukemia and acute myeloid leukemia. Amsparity Treatment of certain inflammatory Pfizer Dec-19 Positive opinion (adalimumab) and autoimmune disorders Recarbrio Treatment of infections due to Merck Sharp & (imipenem/ aerobic Gram-negative organisms Dec-19 Positive opinion Dohme cilastatin/ in adults with limited treatment relebactam) options Beovu Treatment of neovascular (wet) Novartis Dec-19 Positive opinion (brolucizumab) age-related macular degeneration Re-examination of October Hopveus (sodium D&A Pharma Treatment of alcohol dependence Nov-19 2019 negative opinion oxybate) requested by the company

7 / April 2020 © Informa UK Ltd 2020 (Unauthorized photocopying prohibited.) Withdrawn by the company. Kiadis said it decided to Treatment of patients with blood withdraw its application Luxceptar (viable Kiadis Pharma cancers who are receiving a type Nov-19 because of the Agency’s view T-cells) of blood stem cell transplant that the current evidence was not sufficient to conclude on the effectiveness of treatment Withdrawn by company. Aradigm said it decided to For treating and preventing withdraw its application flare-ups of bronchiectasis in Aradigm Linhaliq because the data provided patients with long-term lung Nov-19 Pharmaceuticals (ciprofloxacin) did not allow the CHMP infection caused by Pseudomonas to conclude on a positive aeruginosa bacteria benefit-risk balance for the medicine Extension of indication to include use in combination with rituximab Revlimid (anti-CD20 antibody) for the Celgene Nov-19 Positive opinion, extension (lenalidomide) treatment of adult patients with previously treated follicular lymphoma (Grade 1 – 3a) Extension of indication to include use as a single agent for the adjuvant treatment of adult Kadcyla patients with HER2-positive Roche (trastuzumab early breast cancer who have Nov-19 Positive opinion, extension emtansine) residual invasive disease, in the breast and/or lymph nodes, after neoadjuvant taxane-based and HER2-targeted therapy Treatment of chronic iron Deferasirox Accord overload due to blood Accord Healthcare Nov-19 Positive opinion (deferasirox) transfusions in patients with beta thalassemia and other anemias Clopidogrel/ Acetylsalicylic acid Secondary prevention of Mylan Nov-19 Positive opinion Mylan (clopidogrel / atherothrombotic events acetylsalicylic acid) Rigel Tavlesse Treatment of primary immune Nov-19 Positive opinion Pharmaceuticals (fostamatinib) thrombocytopenia Treatment of excessive daytime Jazz Sunosi sleepiness in patients with Nov-19 Positive opinion Pharmaceuticals (solriamfetol) narcolepsy and obstructive sleep apnea Polivy (polatuzumab Treatment of relapsed/refractory Positive opinion, conditional, Roche Nov-19 vedotin) diffuse large B-cell lymphoma further data will be required Treatment of adult patients with Mayzent Novartis secondary progressive multiple Nov-19 Positive opinion (siponimod) sclerosis with active disease Isturisa Novartis Treatment of Cushing’s syndrome Nov-19 Positive opinion (osilodrostat) Withdrawn by company. Emmaus Life Emmaus said the withdrawal Xyndari (glutamine) Treatment of sickle cell disease Oct-19 Sciences is based on a change in the company’s marketing strategy

8 / April 2020 © Informa UK Ltd 2020 (Unauthorized photocopying prohibited.) Withdrawn by company. Paratek said it decided to Treatment of community-acquired withdraw its application Paratek Nuzyra ( bacterial pneumonia and bacterial because it would not be Oct-19 Pharmaceuticals omadacycline) infections of the skin and skin commercially feasible to structures market Nuzyra just for the treatment of skin and skin structure infections Withdrawn by company. Sun said it decided to withdraw its Sun Ekesivy Treatment of muscle disorders application because it could Pharmaceutical Oct-19 (diclofenamide) called periodic paralysis not address the agency’s Industries concerns within the available time frame Extension of indication to add Negative opinion, on re- Translarna the treatment of patients with PTC Therapeutics Oct-19 examination by CHMP, (ataluren) Duchenne muscular dystrophy indication not extended who are no longer able to walk Extension of indication to add treatment of previously untreated Negative opinion, on re- Revolade patients with severe aplastic Novartis Oct-19 examination by CHMP, (eltrombopag) anemia from 12 years of age indication not extended who cannot have stem cell transplantation Indication extended to include Toujeo (insulin treatment of diabetes mellitus in Sanofi Oct-19 Positive opinion, extension glargine) adolescents and children from the age of six years Extension of indication for use as monotherapy or in combination with platinum and 5-fluorouracil (5-FU) chemotherapy for the first- Merck Sharp & Keytruda line treatment of metastatic or Oct-19 Positive opinion, extension Dohme (pembrolizumab) unresectable recurrent head and neck squamous cell carcinoma in adults whose tumors express PD- L1 with a CPS ≥ 1 Extension of indication to include use in infants aged at least six months, toddlers and children weighing 5kg to less than 25kg Vertex with cystic fibrosis who have Kalydeco (ivacaftor) Oct-19 Positive opinion, extension Pharmaceuticals one of the following gating (class III) mutations in the CFTR gene: G551D, G1244E, G1349D, G178R, G551S, S1251N, S1255P, S549N or S549R Extension of indication to include use in combination with lenalidomide and dexamethasone or with bortezomib, melphalan Darzalex Janssen-Cilag and prednisone for the treatment Oct-19 Positive opinion, extension (daratumumab) of adult patients with newly diagnosed multiple myeloma who are ineligible for autologous stem cell transplant

9 / April 2020 © Informa UK Ltd 2020 (Unauthorized photocopying prohibited.) Vanflyta Treatment of adults with acute Daiichi Sankyo Oct-19 Negative opinion (quizartinib) myeloid leukemia Treatment of alcohol dependence Hopveus (sodium in patients in whom other D&A Pharma Oct-19 Negative opinion oxybate) treatments are not effective or cannot be used Treatment of postmenopausal Evenity Positive opinion, confirmed UCB Pharma women with severe osteoporosis Oct-19 (romosozumab) on re-examination by CHMP at high risk of fracture For reducing the duration of Pegfilgrastim Mundipharma neutropenia and the incidence Mundipharma Oct-19 Positive opinion Biologics of febrile neutropenia due to (pegfilgrastim) chemotherapy For combination treatment in Spravato Janssen-Cilag adults with treatment-resistant Oct-19 Positive opinion (esketamine) major depressive disorder Rinvoq AbbVie Treatment of rheumatoid arthritis Oct-19 Positive opinion (upadacitinib) Treatment of acute bacterial skin and skin structure infections Quofenix Menarini Group in adults when it is considered Oct-19 Positive opinion (delafloxacin) inappropriate to use other antibacterial agents Treatment of severe hypoglycemia Eli Lilly Baqsimi (glucagon) in patients with diabetes aged Oct-19 Positive opinion four years and older For active immunization of Ervebo (Ebola Zaire Merck Sharp & individuals aged 18 years and Positive opinion, conditional, Vaccine (rVSVΔG- Oct-19 Dohme older at risk of infection with the further data will be required ZEBOV-GP, live) Ebola virus Emmaus Life Xyndari (glutamine) Treatment of sickle cell disease Sep-19 Withdrawn by the company Sciences The indication for Trulicity has been changed - the wording now says that Trulicity is indicated for the treatment of adults with insufficiently controlled type 2 diabetes mellitus as an adjunct Trulicity Lilly to diet and exercise: (i) as Sep-19 Positive opinion, extension (dulaglutide) monotherapy when metformin is considered inappropriate due to intolerance or contraindications; (ii) in addition to other medicinal products for the treatment of diabetes Extension of indication to include use in combination with androgen-deprivation therapy, Taxotere Aventis Pharma with or without prednisone or Sep-19 Positive opinion, extension (docetaxel) prednisolone, for the treatment of patients with metastatic hormone- sensitive prostate cancer

10 / April 2020 © Informa UK Ltd 2020 (Unauthorized photocopying prohibited.) Inclusion of a new route of administration, strength and pharmaceutical form: Remsima 120mg solution for injection for Celltrion Remsima subcutaneous use in pre-filled Sep-19 Positive opinion, extension Healthcare (infliximab) pens or syringes (Remsima for subcutaneous use is authorized only in the rheumatoid arthritis indication) Extension of indication to Lucentis Novartis include use as a treatment for Sep-19 Positive opinion, extension (ranibizumab) proliferative diabetic retinopathy Extension of indication to include use as an add-on therapy with intranasal corticosteroids for the treatment of adults with severe Dupixent Sanofi chronic rhinosinusitis with nasal Sep-19 Positive opinion, extension (dupilumab) polyposis for whom therapy with systemic corticosteroids and/or surgery do not provide adequate disease control Extension of indication to include use in combination with prednisone or prednisolone for Docetaxel Zentiva Zentiva the treatment of patients with Sep-19 Positive opinion, extension (docetaxel) hormone refractory metastatic castration-resistant prostate cancer The indication for Benlysta has been changed - it is still indicated for use in adults but now the wording says it can be used as add-on therapy in patients aged Benlysta 5 years and older with active, GlaxoSmithKline Sep-19 Positive opinion, extension (belimumab) autoantibody-positive systemic lupus erythematosus with a high degree of disease activity (eg, positive anti dsDNA and low complement) despite standard therapy Extension of indication to use in combination with axitinib for Bavencio Merck the first-line treatment of adult Sep-19 Positive opinion, extension (avelumab) patients with advanced renal cell carcinoma Treatment of acute lymphoblastic Orphelia Pharma Ivozall (clofarabine) Sep-19 Positive opinion leukemia in pediatric patients Bortezomib Treatment of multiple myeloma Fresenius Kabi Fresenius Kabi Sep-19 Positive opinion and mantle cell lymphoma (bortezomib) Arsenic trioxide Treatment of acute promyelocytic Accord Healthcare Accord (arsenic Sep-19 Positive opinion leukemia trioxide) Plethora Pharma Senstend (lidocaine/ Treatment of premature Positive opinion, informed Sep-19 Solutions prilocaine) ejaculation in adult men consent

11 / April 2020 © Informa UK Ltd 2020 (Unauthorized photocopying prohibited.) Aerie Rhokiinsa Treatment of patients with Sep-19 Positive opinion Pharmaceuticals (netarsudil) glaucoma or ocular hypertension Qtrilmet (metformin hydrochloride/ Treatment of type 2 diabetes AstraZeneca Sep-19 Positive opinion saxagliptin/ mellitus dapagliflozin) Treatment of adult patients who have relapsed or refractory acute Astellas Pharma Xospata (gilteritinib) Sep-19 Positive opinion myeloid leukemia with a FLT3 mutation Extension of indication to add Re-examination of June 2019 Translarna the treatment of patients with PTC Therapeutics Jul-19 negative opinion requested (ataluren) Duchenne muscular dystrophy by the company who can no longer walk Extension of indication to include Re-examination of June 2019 Revolade treatment of previously untreated Novartis Jul-19 negative opinion requested (eltrombopag) patients with severe aplastic by the company anemia from 2 years of age Re-examination of June 2019 Evenity UCB Pharma Treatment of osteoporosis Jul-19 negative opinion requested (romosozumab) by the company Extension of indication to Zerbaxa Merck Sharp & include treatment of hospital- (ceftolozane/ Jul-19 Positive opinion, extension Dohme acquired pneumonia, including tazobactam) ventilator-associated pneumonia Extension of indication to include use in combination with nab paclitaxel and carboplatin for the first-line treatment of adult patients with metastatic non- squamous non-small cell lung Tecentriq cancer who do not have EGFR Roche Jul-19 Positive opinion, extension (atezolizumab) mutant or ALK positive NSCLC. Also, extension of indication to include use in combination with carboplatin and etoposide for the first-line treatment of adult patients with extensive-stage small cell lung cancer. Extension of indication to include the treatment of adult patients with moderately to severely active ulcerative colitis who have Stelara had an inadequate response Janssen-Cilag Jul-19 Positive opinion, extension (ustekinumab) with, lost response to, or were intolerant to either conventional therapy or a biologic or have medical contraindications to such therapies Extension of indication to include treatment of neuromyelitis optica Alexion spectrum disorder in patients Soliris (eculizumab) Jul-19 Positive opinion, extension Pharmaceuticals who are anti-aquaporin-4 (AQP4) antibody-positive with a relapsing course of the disease

12 / April 2020 © Informa UK Ltd 2020 (Unauthorized photocopying prohibited.) Extension of indication to use in preterm infants for the treatment of retinopathy of prematurity Lucentis Novartis (ROP) with zone I (stage 1+, 2+, Jul-19 Positive opinion, extension (ranibizumab) 3 or 3+), zone II (stage 3+) or AP- ROP (aggressive posterior ROP) disease Extension of indication to use as monotherapy for the treatment of adult patients with metastatic gastric cancer including adenocarcinoma of the gastroesophageal junction, who have been previously treated with at least two prior systemic treatment regimens for advanced disease. The existing indication for Les Laboratoires Lonsurf (trifluridine/ colorectal cancer has also been Jul-19 Positive opinion, extension Servier tipiracil) changed to use as monotherapy for the treatment of adult patients with metastatic colorectal cancer who have been previously treated with, or are not considered candidates for, available therapies including fluoropyrimidine-, oxaliplatin- and irinotecan-based chemotherapies, anti-VEGF agents, and anti EGFR agents Extension of indication to include use in combination with axitinib Merck Sharp & Keytruda for the first-line treatment of Jul-19 Positive opinion, extension Dohme (pembrolizumab) advanced renal cell carcinoma in adults Extension of indication to include use in combination with pomalidomide and dexamethasone for the treatment of adult patients with relapsed Bristol-Myers Empliciti and refractory multiple myeloma Jul-19 Positive opinion, extension Squibb (elotuzumab) who have received at least two prior therapies including lenalidomide and a proteasome inhibitor and have demonstrated disease progression on the last therapy Treatment of chronic iron overload due to blood transfusions in patients with Deferasirox Mylan Mylan beta thalassemia major, Jul-19 Positive opinion (deferasirox) non-transfusion-dependent thalassemia syndromes and other anemias Trogarzo Theratechnologies Treatment of HIV infection Jul-19 Positive opinion (ibalizumab) Acorda Treatment of symptoms of off Inbrija (levodopa) Jul-19 Positive opinion Therapeutics periods in Parkinson’s disease

13 / April 2020 © Informa UK Ltd 2020 (Unauthorized photocopying prohibited.) Treatment of seizures associated Epidyolex GW Pharma with Lennox-Gastaut syndrome or Jul-19 Positive opinion (cannabidiol) Dravet syndrome Treatment of patients with Vitrakvi solid tumors that display a Positive opinion, conditional, Bayer Jul-19 (larotrectinib) neurotrophic tyrosine receptor further data will be required kinase (NTRK) gene fusion

14 / April 2020 © Informa UK Ltd 2020 (Unauthorized photocopying prohibited.) New EU Approvals

Executive Summary through the centralized procedure. The European The Pink Sheet’s list of EU centralized approvals Medicines Agency’s Committee for Medicinal of new active substances has been updated with Products for Human Use (the CHMP) carries out three new products including Novartis’s Beovu a scientific assessment of the initial marketing for treating neovascular (wet) age related macular authorization application (MAA) and gives a degeneration. The list, which contains information recommendation on whether the medicine should dating back to January 2018, includes brand name, be marketed or not. CHMP recommendations generic name, company, therapeutic indication, are forwarded to the European Commission for a date of marketing authorization and product type legally binding decision. (eg, medicine, vaccine, biologic). Once granted, centralized marketing authorizations are valid in all EU member states as well as in the European Economic Area countries The Pink Sheet’s regularly updated list of products of Iceland, Liechtenstein and Norway. containing new active substances that have been approved for marketing in the EU under the The list is updated regularly with new approvals centralized authorization procedure now includes and is current as of 20 February 2020. It includes three new products. information dating back to January 2018.

The great majority of new, innovative medicines Please note: and vaccines that are marketed in the EU go Data in the following table is a sample only.

Date of Marketing Product Company Brand/Generic Name Indication Authorization Type/Status Announcement Respiratory - maintenance Fasenra AstraZeneca treatment for severe eosinophilic 8-Jan-18 Biologic (benralizumab) asthma Roche Ocrevus (ocrelizumab) CNS - multiple sclerosis 8-Jan-18 Biologic Adynovi (rurioctocog Shire Pharmaceuticals Blood disorders - hemophilia A 8-Jan-18 Biologic alfa pegol) Infectious diseases - prophylaxis of cytomegalovirus reactivation Medicine, Merck Sharp & Dohme Prevymis (letermovir) and disease in adult CMV- 8-Jan-18 orphan seropositive recipients of allogeneic hematopoietic stem cell transplant Metabolic - adults with insufficiently Novo Nordisk Ozempic (semaglutide) 8-Feb-18 Medicine controlled type 2 diabetes Hemlibra Roche/Chugai Blood disorders - hemophilia A 18-Feb-18 Biologic (emicizumab) Biologic, Metabolic - X-linked orphan, Kyowa Kirin Crysvita (burosumab) 19-Feb-18 hyperphosphatemia conditional approval

15 / April 2020 © Informa UK Ltd 2020 (Unauthorized photocopying prohibited.) Steglatro Merck Sharp & Dohme Metabolic - type 2 diabetes 21-Mar-18 Medicine (ertugliflozin)* Infectious diseases - prevention Shingrix (recombinant GlaxoSmithKline of herpes zoster/post-herpetic varicella zoster 21-Mar-18 Vaccine Biologicals neuralgia in adults 50 years and vaccine) over Lokelma (sodium Metabolic - oral potassium AstraZeneca 22-Mar-18 Medicine zirconium cyclosilicate) removing agent for hyperkalemia Steglujan (ertugliflozin/ Merck Sharp & Dohme Metabolic - type 2 diabetes 23-Mar-18 Medicne sitagliptin) Advanced Immunology/Gastrointestinal - an therapy allogeneic stem cell therapy for Tigenix/Takeda Alofisel (darvadstrocel) 23-Mar-18 medicinal complex perianal fistulas in Crohn’s product, disease orphan Segluromet (ertugliflozin/ Merck Sharp & Dohme Metabolic - type 2 diabetes 23-Mar-18 Medicine metformin hydrochloride) Biologic, orphan, Lamzede (velmanase Genetic disorders - alpha- Chiesi Farmaceutici 23-Mar-18 exceptional alfa) mannidosis circumstances approval Infectious diseases - uncomplicated BioCryst UK Alpivab (peramivir) influenza in adults and children 13-Apr-18 Medicine from two years of age Mylotarg Biologic, Pfizer (gemtuzumab Cancer - acute myeloid leukemia 19-Apr-18 orphan ozogamicin) Medicine, Clovis Oncology Rubraca (rucaparib) Cancer - ovarian neoplasms 24-May-18 orphan Biktarvy (bictegravir/ Infectious diseases - HIV infection emtricitabine/ in adults without present or Gilead Sciences tenofovir alafenamide) past evidence of viral resistance 21-Jun-18 Medicine - bictegravir is the new to the integrase inhibitor class, active substance emtricitabine or tenofovir Neurologic - for treatment of Medicine, Akcea Therapeutics stage 1 or stage 2 polyneuropathy orphan, Tegsedi (inotersen) 6-Jul-18 (Ionis Pharmaceuticals) in patients with hereditary accelerated transthyretin amyloidosis (hATTR) assessment Otsuka Rxulti (brexpiprazole) Neurologic - schizophrenia in adults 26-Jul-18 Medicine Analgesics - for prophylaxis of Novartis Aimovig (erenumab) migraine in adults who have at least 26-Jul-18 Biologic 4 migraine days per month Alimentary tract and metabolism - an adjunct to diet as a Aegerion Biologic, Myalepta (metreleptin) replacement therapy to treat the 30-Jul-18 Pharmaceuticals orphan complications of leptin deficiency in lipodystrophy (LD) patients

16 / April 2020 © Informa UK Ltd 2020 (Unauthorized photocopying prohibited.) Cancer - pediatric and young adult patients up to 25 years of age with Advanced B cell acute lymphoblastic leukemia therapy that is refractory, in relapse medicinal Kymriah Novartis post transplant or in second or 23-Aug-18 product, (tisagenlecleucel) later relapse. Adult patients with orphan, relapsed or refractory diffuse large accelerated B cell lymphoma after two or more assessment lines of systemic therapy Cancer - adults with relapsed Advanced or refractory diffuse large B-cell therapy Yescarta (axicabtagene Kite Pharma lymphoma and primary mediastinal 23-Aug-18 medicinal ciloleucel) large B-cell lymphoma, after two or product, more lines of systemic therapy orphan Biologic, Metabolism - non- orphan, Mepsevii (vestronidase neurological manifestations of Ultragenyx 23-Aug-18 exceptional alfa) Mucopolysaccharidosis VII (MPS VII; circumstances Sly syndrome) approval Neurologic - hereditary Medicine, transthyretin-mediated (hATTR) orphan, Alnylam Onpattro (patisiran) 27-Aug-18 amyloidosis in adults with Stage 1 accelerated or Stage 2 polyneuropathy assessment Cancer - extended adjuvant treatment of adult patients with early stage hormone receptor positive HER2-overexpressed/ Puma Biotechnology Nerlynx (neratinib) 31-Aug-18 Medicine amplified breast cancer and who are less than one year from the completion of prior adjuvant trastuzumab based therapy Antithrombotic - adults experiencing an episode of acquired thrombotic Biologic, Ablynx/Sanofi Cablivi (caplacizumab) 31-Aug-18 thrombocytopenic purpura orphan (aTTP), in conjunction with plasma exchange and immunosuppression Immunology, Dermalology - adults Ilumetri with moderate to severe plaque Almirall 17-Sep-18 Biological (tildrakizumab) psoriasis who are candidates for systemic therapy Cancer - for use in combination with encorafenib for the treatment Pierre Fabre Mektovi (binimetinib) of adult patients with unresectable 20-Sep-18 Medicine Médicament or metastatic melanoma with a BRAF V600 mutation Cancer - for use in combination with binimetinib for the treatment Pierre Fabre Braftovi (encorafenib) of adult patients with unresectable 20-Sep-18 Medicine Médicament or metastatic melanoma with a BRAF V600 mutation Tetraphase Infectious disease - complicated Xerava (eravacycline) 20-Sep-18 Medicine Pharmaceuticals intra-abdominal infections in adults

17 / April 2020 © Informa UK Ltd 2020 (Unauthorized photocopying prohibited.) Cancer - for use as monotherapy for the treatment of locally advanced, unresectable non-small cell lung cancer in adults whose AstraZeneca Imfinzi (durvalumab) 21-Sep-18 Biologic tumors express PD-L1 on ≥ 1% of tumor cells and whose disease has not progressed following platinum based chemoradiation therapy Cancer - treatment of women with hormone receptor (HR) positive, human epidermal growth factor receptor 2 (HER2) negative locally Verzenios advanced or metastatic breast Eli Lilly 27-Sep-18 Medicine (abemaciclib) cancer in combination with an aromatase inhibitor or fulvestrant as initial endocrine-based therapy, or in women who have received prior endocrine therapy Genetic disorders - Indicated for use in a combination regimen with ivacaftor 150mg tablets for the treatment of patients with cystic fibrosis (CF) aged 12 years and older who are homozygous for the F508del mutation or Vertex Symkevi (tezacaftor/ who are heterozygous for the Medicine, 31-Oct-18 Pharmaceuticals ivacaftor) F508del mutation and have one orphan of the following mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene: P67L, R117C, L206W, R352Q, A455E, D579G, 711+3A�G, S945L, S977F, R1070W, D1152H, 2789+5G�A, 3272 26A�G, and 3849+10kbC�T Infectious diseases -treatment of the following infections in adults: complicated urinary tract infection (cUTI), including pyelonephritis; complicated intra-abdominal infection (cIAI); hospital-acquired pneumonia (HAP), including Vabomere ventilator associated pneumonia Rempex (meropenem/ (VAP). Treatment of patients 20-Nov-18 Medicine Pharmaceuticals vaborbactam) with bacteremia that occurs in association with, or is suspected to be associated with, any of the infections listed above. Also for the treatment of infections due to aerobic Gram-negative organisms in adults with limited treatment options Genetic disorders - for routine Biologic, Takhzyro prevention of recurrent attacks of orphan, Shire 22-Nov-18 (lanadelumab) hereditary angioedema in patients accelerated aged 12 years and older assessment

18 / April 2020 © Informa UK Ltd 2020 (Unauthorized photocopying prohibited.) Ophthalmic - treatment of adult Advanced and pediatric patients with vision therapy Luxturna (voretigene loss due to inherited retinal Spark Therapeutics 22-Nov-18 medicinal neparvovec) dystrophy caused by confirmed product, biallelic RPE65 mutations and who orphan drug have sufficient viable retinal cells Cancer - for use as a monotherapy for the treatment of adult patients with anaplastic lymphoma kinase- Takeda Alunbrig (brigatinib) 22-Nov-18 Medicine positive advanced non-small cell lung cancer previously treated with crizotinib Infectious diseases - treatment of adult patients with mycosis Poteligeo Biologic, Kyowa Kirin fungoides or Sézary syndrome who 22-Nov-18 (mogamulizumab) orphan have received at least one prior systemic therapy Blood disorders - treatment and prophylaxis of bleeding in Jivi (damoctocog alfa Biologic, Bayer previously treated patients ≥ 12 22-Nov-18 pegol) orphan drug years of age with hemophilia A (congenital factor VIII deficiency) Infectious diseases - treatment Delstrigo (doravirine/ of adults infected with HIV 1 Merck Sharp & Dohme lamivudine/ tenofovir without past or present evidence 22-Nov-18 Medicine disoproxil) of resistance to the NNRTI class, lamivudine, or tenofovir Infectious diseases - for use in combination with other antiretroviral medicinal products, Merck Sharp & Dohme Pifeltro (doravirine) for the treatment of adults infected 22-Nov-18 Medicine with HIV 1 without past or present evidence of resistance to the NNRTI class Indicated for the prevention of dengue disease caused by dengue Dengvaxia (dengue virus serotypes 1, 2, 3 and 4 in Sanofi tetravalent vaccine 12-Dec-18 Vaccine individuals 9 to 45 years of age with (live, attenuated)) prior dengue virus infection and living in endemic areas

Executive Summary and therapeutic area. For generic and biosimilar New medicines under evaluation at the European medicines, it provides the INN (active moiety only, Medicines Agency. with no information on salt, ester or derivative) and therapeutic area. The CHMP monthly meeting agendas sometimes identify the name of sponsors of orphan drugs only. This is a regularly updated list of products that have been filed with the European Medicines The EMA only lists information on medicines Agency’s Committee for Medicinal Products for whose applications have been validated at the Human Use (CHMP) under the EU’s centralized time the agency’s list in question or CHMP agenda authorization procedure. is compiled.

The information is based on the EMA’s monthly Information on CHMP opinions and on EU updated list of medicines under review at approvals can be found elsewhere in the EU the agency, CHMP monthly meeting agendas, Performance Tracker section of the Pink Sheet company press releases, and original research website. by the Pink Sheet. The latest list from the EMA was compiled on 7 February. (Also see “Potential Information on the different types of applications Cardiovascular Blockbuster Inclisiran Among New or approval pathways involved – for example, Filings At EMA” - Pink Sheet, 14 Feb, 2020.) accelerated assessment, informed consent application, conditional approval – is provided in The EMA does not identify in its own list footnotes below the table. the sponsors of marketing authorization applications that are under review. It gives only Please note: the international non-proprietary name (INN) Data in the following table is a sample only.

Date of EMA list Therapeutic area or Product Type/ Company INN compilation, CHMP agenda, indication Status or company press release not known risperidone psycholeptic February 7 2020 generic not known lenalidomide immunosuppressant February 7 2020 generic not known doxorubicin antineoplastic medicine February 7 2020 generic not known bevacizumab antineoplastic medicine February 7 2020 biosimilar fedratinib (US Celgene brand name treatment of myelofibrosis February 7 2020 medicine, orphan Inrebic) treatment of relapsed medicine, orphan, belantamab GlaxoSmithKline or refractory multiple February 7 2020 accelerated mafodotin myeloma assessment

20 / April 2020 © Informa UK Ltd 2020 (Unauthorized photocopying prohibited.) Date of EMA list Therapeutic area or Product Type/ Company INN compilation, CHMP agenda, indication Status or company press release KTE-X19 (autologous peripheral blood T cells CD4 and CD8 selected and CD3 and CD28 activated treatment of relapsed ATMP, orphan, Kite transduced with or refractory mantle cell February 7 2020 accelerated retroviral vector lymphoma assessment expressing anti- CD19 CD28/ CD3-zeta chimeric antigen receptor and cultured) treatment of patients with locally advanced or Seattle Genetics tucatinib February 7 2020 medicine metastatic HER2-positive breast cancer treatment of RET-mutant medullary thyroid cancer, advanced RET fusion- Lilly selpercatinib positive non-small cell February 7 2020 medicine lung cancer and RET fusion-positive thyroid cancer Perjeta treatment of patients (pertuzumab)/ Roche with HER2-positive breast February 7 2020 medicine Herceptin cancer (trastuzumab) treatment of relapsing Novartis ofatumumab February 7 2020 medicine forms of multiple sclerosis Novartis inclisiran lipid modifying medicine February 7 2020 medicine treatment of aromatic PTC-AADC L-amino acid PTC Therapeutics (eladocagene January 13 2020 medicine, orphan decarboxylase (AADC) exuparvovec) deficiency for use in combination with other antiretrovirals for the treatment of adults with multidrug resistant medicine, HIV-1 infection for whom ViiV Healthcare fostemsavir January 10 2020 accelerated it is otherwise not possible assessment to construct a suppressive antiviral regimen due to resistance, intolerance or safety considerations not known glucagon pancreatic hormones January 6 2020 generic not known azathioprine immunosuppressant January 6 2020 generic Paion remimazolam for procedural sedation January 6 2020 medicine

21 / April 2020 © Informa UK Ltd 2020 (Unauthorized photocopying prohibited.) Date of EMA list Therapeutic area or Product Type/ Company INN compilation, CHMP agenda, indication Status or company press release adjunctive treatment to levodopa-based regimens istradefylline (KW- Kyowa Kirin in adult patients with January 6 2020 medicine 6002) Parkinson’s disease experiencing “off” time treatment of patients with relapsed or refractory chronic lymphocytic Verastem duvelisib (Copiktra) leukemia/small January 6 2020 medicine, orphan lymphocytic lymphoma and relapsed or refractory follicular lymphoma netarsudil and for reducing elevated Aerie latanoprost intraocular pressure in January 6 2020 medicine Pharmaceuticals (Roclanda) patients with glaucoma treatment of adults with locally advanced or metastatic cholangiocarcinoma with a fibroblast growth factor Incyte pemigatinib January 6 2020 medicine, orphan receptor 2 (FGFR2) fusion or rearrangement that is relapsed or refractory after at least one line of systemic therapy treatment of adults with relapsed or refractory moxetumomab hairy cell leukemia who Innate Pharma pasudotox have received at least two January 6 2020 medicine, orphan (Lumoxiti) prior systemic therapies, including treatment with a purine nucleoside analog medicine, BioMarin valoctocogene treatment of adults with accelerated January 6 2020 Pharmaceutical roxaparvovec severe hemophilia A assessment, orphan potassium citrate/ treatment of distal renal potassium tubular acidosis (dRTA) in Advicenne Pharma December 9 2019 medicine, orphan hydrogen patients aged six months carbonate and older QVM149 (indacaterol, Novartis asthma December 2 2019 medicine glycopyrronium and mometasone) icosapent ethyl cardiovascular risk Amarin (Vascepa - US December 2 2019 medicine reduction name) baloxavir marboxil Roche treatment of flu December 2 2019 medicine (Xofluza - US name)

22 / April 2020 © Informa UK Ltd 2020 (Unauthorized photocopying prohibited.) Date of EMA list Therapeutic area or Product Type/ Company INN compilation, CHMP agenda, indication Status or company press release OTL-200 (autologous CD34+ cell enriched population that contains hematopoietic gene therapy for ATMP, orphan, Orchard stem and metachromatic December 2 2019 accelerated Therapeutics progenitor cells leukodystrophy assessment transduced ex vivo using a lentiviral vector encoding the human arylsulfatase a gene) vaccine, Janssen Ad26.ZEBOV Ebola Zaire vaccine November 7 2019 accelerated assessment vaccine, Janssen MVA-BN-Filo Ebola Zaire vaccine November 7 2019 accelerated assessment fluticasone (propionate)/ not known treatment of asthma November 4 2019 medicine salmeterol (xinafoate) influenza Sanofi quadrivalent influenza vaccine November 4 2019 vaccine vaccine (rDNA) Meningococcal immunization against group A, C, W135 Neisseria meningitidis Sanofi November 4 2019 vaccine and Y conjugate serogroups A, C, W-135 vaccine and Y treatment of primary not known caffeine citrate November 4 2019 generic apnoea treatment of diabetes Biocon/Mylan insulin aspart November 4 2019 biosimilar mellitus treatment of gastrointestinal stromal tumor and metastatic not known sunitinib November 4 2019 generic renal cell carcinoma and pancreatic neuroendocrine tumors treatment of adult patients with chronic AstraZeneca acalabrutinib lymphocytic leukemia/ November 4 2019 medicine, orphan small lymphocytic lymphoma treatment of chronic hepatitis delta virus (HDV) medicine, orphan, MYR bulevirtide infection in adult patients November 4 2019 accelerated Pharmaceuticals (acetate) with compensated liver assessment disease

23 / April 2020 © Informa UK Ltd 2020 (Unauthorized photocopying prohibited.) Date of EMA list Therapeutic area or Product Type/ Company INN compilation, CHMP agenda, indication Status or company press release elexacaftor/ medicine, orphan, Vertex tezacaftor/ivacaftor treatment of cystic fibrosis November 4 2019 accelerated Pharmaceuticals [Trikafta - US assessment name] reducing neutropenia due not known pegfilgrastim October 3 2019 biosimilar to chemotherapy not known bevacizumab antineoplastic medicine October 3 2019 biosimlar treatment of prostate not known abiraterone October 3 2019 generic cancer not known lenalidomide immunosuppressant October 3 2019 generic pituitary and Novo Nordisk somapacitan hypothalamic hormones October 3 2019 medicine, orphan and analogues treatment of adult and medicine, orphan, adolescent patients with Roche satralizumab October 3 2019 accelerated neuromyelitis optica assessment spectrum disorder prevention of not known rivaroxaban September 2 2019 generic atherothrombotic events not known pegfilgrastim immunostimulant September 2 2019 biosimilar treatment of multiple not known fampridine September 2 2019 generic sclerosis not known dasatinib antineoplastic medicine September 2 2019 generic treatment of asthma budesonide/ not known and chronic obstructive September 2 2019 generic formoterol pulmonary disease treatment of relapsed not known arsenic trioxide acute promyelocytic September 2 2019 generic leukemia treatment of adults with Gilead Sciences filgotinib September 2 2019 medicine rheumatoid arthritis for use in combination Janssen rilpivirine with cabotegravir to treat September 2 2019 medicine HIV-1 for use in combination ViiV Healthcare cabotegravir with rilpivirine to treat September 2 2019 medicine HIV-1 for detecting loss of functional dopaminergic not known ioflupane (123I) August 7 2019 generic neuron terminals in the striatum treatment of metastatic carcinoma of the colon or rectum, metastatic breast cancer and recurrence Samsung Bioepis bevacizumab (SB8) August 7 2019 biosimilar of platinum-sensitive epithelial ovarian, fallopian tube or primary peritoneal cancer

24 / April 2020 © Informa UK Ltd 2020 (Unauthorized photocopying prohibited.) Date of EMA list Therapeutic area or Product Type/ Company INN compilation, CHMP agenda, indication Status or company press release Aimmune arachis hypogaea treatment of peanut August 7 2019 medicine Therapeutics allergens (AR101) allergy treatment of acute hepatic medicine, orphan, Alnylam porphyria in adults and givosiran August 7 2019 accelerated Pharmaceuticals adolescents aged 12 years assessment and older treatment of lung infection as part of Insmed amikacin (Arikayce) August 7 2019 medicine, orphan combination antibacterial drug regiment in adults treatment of adult patients with PDGFRα D842V mutant Blueprint Medicines avapritinib gastrointestinal stromal August 7 2019 medicine, orphan tumors (GIST), regardless of prior therapy, and fourth-line GIST treatment of neovascular Molecular Partners/ abicipar pegol age-related macular August 7 2019 medicine Allergan degeneration treatment of patients Sanofi isatuximab with relapsed/refractory July 10 2019 medicine, orphan multiple myeloma treatment of diabetes Sanofi insulin aspart July 9 2019 biosimilar mellitus not known trastuzumab antineoplastic medicine July 9 2019 biosimilar not known doxorubicin antineoplastic medicine July 9 2019 generic not known dasatinib treatment of leukemia July 9 2019 generic prevention of venous not known apixaban July 9 2019 generic thromboembolic events treatment of inhalational Elusys Therapeutics obiltoxaximab anthrax due to Bacillus July 9 2019 medicine, orphan anthracis treatment of sickle cell Novartis crizanlizumab July 9 2019 medicine, orphan disease treatment of community- Nabriva acquired pneumonia in lefamulin July 9 2019 medicine Therapeutics adults 18 years of age and older Pacira BioSciences bupivacaine for postsurgical analgesia July 9 2019 medicine

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