Specialty Pipeline Monthly Update Critical updates in an ever changing environment September 2018 New drug information ● Tiglutik™ (riluzole): ITF Pharma received Food and Drug Administration (FDA) approval of Tiglutik for the treatment of amyotrophic lateral sclerosis (ALS). Tilgutik is this first formulation of riluzole available as a liquid which may provide ease of administration in ALS patients who have trouble swallowing. Riluzole is also available as both a brand (Rilutek®) and generic tablet. ● Oxervate™ (cenegermin-bkbj): Domped farmaceutici SpA received FDA approval for Oxervate, a recombinant human nerve growth factor, for the treatment of neurotrophic keratitis.1 Oxervate is the first FDA-approved drug for neurotrophic keratitis, a rare disease that can cause loss of corneal sensation and impair corneal health. In two, eight-week randomized controlled studies, complete corneal healing in eight weeks was demonstrated in 70% of patients treated with Oxervate compared to 28% of patients in the placebo eye drop group. Oxervate is not anticipated to launch until early 2019.2 ● Takhzyro™ (lanadelumab-flyo): Shire received FDA approval of Takhzyro, a monoclonal antibody, to prevent attacks of hereditary angioedema (HAE) in patients 12 years of age and older. Takhzyro is self-administered every two weeks as a subcutaneous injection. Dosing every four weeks may be considered in some patients. Takhzyro has launched at an annual wholesale acquisition cost (WAC) of $573,820. CSL Behring’s Haegarda®, also a subcutaneous therapy for the prevention of HAE attacks, uses weight-based dosing and is given twice weekly. The average annual WAC of Haegarda is $488,800 for a patient weighing 66–83 kg, but as weight increases, the dosing and price of Haegarda also increase. ● Jivi™ (antihemophilia factor [recombinant] PEGylated-aucl): Bayer received FDA approval for Jivi for the routine prophylactic treatment of hemophilia A in previously treated adults and in children and adolescents aged 12 years or older. Jivi is also indicated for on-demand treatment and the perioperative management of bleeding in the same patient population. The annual WAC is similar to other extended half-life (EHL) products for hemophilia A. ● Lumoxiti™ (moxetumomab pasudotox-tdfk): The FDA approved AstraZeneca’s and MedImmune’s Lumoxiti for the intravenous treatment of adult patients with relapsed or refractory hairy cell leukemia (HCL) who have received at least two prior systemic therapies, including treatment with a purine nucleoside analog. Lumoxiti is the first CD22-directed cytotoxin for patients with HCL. While the information in this newsletter is from sources we believe to be reliable, we do not warrant that the information in this document is free from error. Use it only as a guide. Statements regarding drugs or manufacturers are not intended as promotion; those statements should not be used to make assumptions about formulary status. Each trademarked drug name is the property of its respective owner. Specialty Pipeline Update: September 2018 Page 2 New indications ● Imbruvica® (ibrutinib): Janssen received expanded approval of Imbruvica for the use in combination with rituximab for treatment of relapsed or refractory and treatment-naive patients with Waldenstrom’s macroglobulinemia (WM), a rare form of non-Hodgkin lymphoma. This approval expands Imbruvia’s use in WM beyond monotherapy to include use with rituximab. ● Actemra® (tocilizumab): The FDA expanded Genentech’s Actemra label to include treatment of the subcutaneous formulation for patients aged two years and older with active systemic juvenile idiopathic arthritis (SJIA). Prior to this approval, only the IV formulation was FDA approved for patients two years of age and older with SJIA. September news ● “Akcea Therapeutics, Inc. an affiliate of Ionis Pharmaceuticals, Inc., announced that they received a Complete Response Letter (CRL) from the Division of Metabolism and Endocrinology Products of the FDA regarding the New Drug Application (NDA) for Waylivra™ (volanesorsen).”3 ● “Sunovion Pharmaceuticals Inc. announced that the FDA issued a CRL for the NDA for dasotraline, a novel dual-acting dopamine and norepinephrine reuptake inhibitor (DNRI), for the treatment of attention-deficit hyperactivity disorder (ADHD).”4 ● “Acorda Therapeutics has suffered its second setback this week, acknowledging that the FDA has extended by three months the PDUFA target decision date for its NDA of its Parkinson’s disease OFF-symptoms candidate Inbrija™ (levodopa inhalation powder).”5 ● “The FDA has accepted for priority review the Biologics License Application for caplacizumab for treatment of patients 18 years of age and older experiencing an episode of aTTP. The target action date for the FDA decision is February 6, 2019.”6 ● “GlaxoSmithKline received a CRL from the FDA regarding its application for mepolizumab as an add-on treatment to inhaled corticosteroid-based maintenance treatment for the reduction of exacerbations in patients with chronic obstructive pulmonary disease (COPD), guided by blood eosinophil counts.”7 Specialty Pipeline Update: September 2018 Page 3 Specialty new product approvals in the past twelve months Route of Generic name Brand name Manufacturer Indication(s) administration Month approved antihemophilia factor Jivi™ Bayer Hemophilia A Intravenous September [recombinant] PEGylated-aucl 2018 lanadelumab-flyo Takhzyro™ Shire Prevention of hereditary Subcutaneous September angioedema 2018 cenegermin-bkbj Oxervate™ Dompe farmaceutici Neurotrophic keratitis Eye drop September SpA 2018 riluzole Tiglutik™ ITF Pharma Amyotrophic lateral sclerosis Oral September (ALS) 2018 stiripentol Diacomit™ Biocodex In combination with clobazam Oral August 2018 for Dravet syndrome migalastat Galafold™ Amicus Fabry disease with an amenable Oral August 2018 Therapeutics GLA variant patisiran Onpattro™ Alnylam Polyneuropathy caused by Intravenous August 2018 hereditary transthyretin- mediated amyloidosis (hATTR) lusutrombopag Mulpleta™ Shionogi Thrombocytopenia in adult Oral August 2018 patients with chronic liver disease who are scheduled to undergo a procedure cannabidiol Epidiolex® GW Pharmaceuticals Lennox-Gastaut syndrome and Oral July 2018 Dravet syndrome baricitinib Olumiant® Lilly/Incyte Rheumatoid arthritis Oral June 2018 pegvaliase-pqpz Palyniziq™ BioMarin Phenylketonuria Subcutaneous June 2018 avatrombopag Doptelet® Dova Thrombocytopenia Oral May 2018 Pharmaceuticals tolvaptan Jynarque™ Otsuka Autosomal dominant polycystic Oral May 2018 kidney disease fostamatinib disodium Tavalisse® Rigel Chronic immune Oral April 2018 hexahydrate thrombocytopenia (ITP) burosumab-twza Crysvita® Ultragenyx and X-linked hypophosphatemia Subcutaneous April 2018 Kyowa Kirin tildrakizumab-asmn Ilumya® Sun Pharmaceutical Plaque psoriasis Subcutaneous April 2018 hydroxyurea Siklos® Addmedica Pediatric sickle cell disease Oral March 2018 ibalizumab-uiyk Trogarzo™ TaiMed Multidrug resistant HIV Intravenous March 2018 Biologics and Theratechnologies hydroxyprogesterone caproate Makena® Amag Reduce the risk of preterm birth Subcutaneous February 2018 injection Pharmaceuticals tezacaftor/ivacaftor; ivacaftor Symdeko™ Vertex Cystic fibrosis Oral February 2018 voretigene neparvovec-rzyl Luxturna™ Sparks Confirmed biallelic RPE65 Subretinal December 2017 Therapeutics mutation-associated retinal injection dystrophy buprenorphine extended Sublocade™ Indivior Opioid use disorder Subcutaneous December 2017 release injection bosentan Tracleer 32 mg Actelion Pulmonary arterial Tablet for oral November 2017 Pharmaceuticals hypertension (PAH) suspension emicizumab-kxwh Hemlibra™ Genentech Hemophilia A with inhibitors Subcutaneous November 2017 vestronidase alfa Mepsevii™ Ultragenyx MPS VII (Sly syndrome) Intravenous November 2017 benralizumab Fasenra™ AstraZeneca Severe asthma Subcutaneous November 2017 Specialty Pipeline Update: September 2018 Page 4 New indications for approved specialty products Generic name Brand name Manufacturer New Indication(s) Date approved methoxy polyethylene glycol- Mircera® Roche Pediatric patients aged 5 to 17 years of age September 2018 epoetin beta on hemodialysis who are switching from another erythropoiesis-stimulating agent (ESA) following hemoglobin stabilization with an ESA rituximab Rituxan® Genentech Pemphigus vulgaris September 2018 tofacitinib citrate Xeljanz® Pfizer Ulcerative colitis September 2018 certolizumab pegol Cimzia® UCB Plaque psoriasis September 2018 denosumab Prolia® Amgen Glucocorticoid-induced osteoporosis May 2018 tocilizumab Actemra® Genentech Subcutaneous formulation to treat May 2018 polyarticular juvenile idiopathic arthritis (IV previously approved) fingolimod Gilenya® Novartis Multiple sclerosis in children and May 2018 adolescents age 10 years and older von Willebrand factor Vonvendi® Shire Perioperative management of bleeding in April 2018 (recombinant) adult patients with von Willebrand disease sargramostim Leukine® Sanofi-Aventis Hematopoietic syndrome of acute radiation April 2018 syndrome (H-ARS) Immune globulin subcutaneous Hizentra® CSL Behring Maintenance therapy in adults with March 2018 (human), 20% liquid chronic inflammatory demyelinating polyneuropathy (CIDP) ferumoxytol Feraheme® AMAG Iron deficiency anemia (IDA) intolerant or February 2018 non-responsive to oral iron therapy somatropin Zomacton® Ferring Adults with growth hormone deficiency February 2018 Pharmaceuticals plecanatide Trulance® Synergy Irritable bowel syndrome February 2018 denosumab Xgeva®