Specialty Pipeline Update

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CLINICAL SOLUTIONS Drug Insights > June 2014 Specialty Pipeline Update New Drug Information Eloctate (recombinant factor VIII Fc fusion protein): Biogen received FDA approval for their hemophilia A for the prevention and treatment of bleeding episodes. Eloctate requires fewer s compared to the previous hemophilia therapies for prophylaxis. June News By law, Dr. Richard Pazdur, the U.S. Food and Drug s cancer drug czar, is not allowed to consider the cost of treatments his agency reviews, only whether they are safe and effective. But Pazdur is not blind to escalating drug prices and the growing debate over how to place an appropriate value on cancer drugs, which can cost $100,000 a year or more a year Pazdur said the solution will likely take a national dialog involving all stakeholder-insurers, patients, doctors, lawmakers. 1 Pharmacyclics announced trial results of the first Phase III study (RESONATE, PCYC-1112-CA), a head-tohead comparison of Imbruvica (ibrutinib) versus Arzerra (ofatumumab) in patients with previously treated chronic lymphocytic leukemia or small lymphocytic lymphoma. Patients receiving Imbruvica realized a significant improvement in progression free survival (PFS), overall survival (OS) and overall response rate (ORR) as compared to patients receiving ofatumumab. As a pill rather than an injectable drug, Janssen s med has another leg up over its competition, and analysts surveyed by Bloomberg expect it to rake in $3.37 billion by 2018. 2 For years, the FDA has been unveiling its plan for regulating knockoffs of blockbuster biologics in fits and starts, this week outlining just how it wants to define biosimilarity for would-be copycat drugs. In a nonbinding draft guidance, the agency spelled out four tiers of possible similarity between an underreview treatment and the approved biologic it hopes to replace. In the best-case scenario, biosimilar developers would need only targeted animal or human studies to prove their drugs match their references, while those deemed not similar would not be further considered without changes to their manufacturing processes. 3 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.

Drug Insights > Specialty Pipeline Update Page 2 Specialty New Product Approvals in the Past Twelve Months recombinant factor VIII Fc fusion protein Eloctate Biogen Hemophilia A Intravenous siltuximab Sylvant Johnson & Johnson Castleman disease Intravenous vedolizumab Entyvio Takeda Ulcerative colitis and Crohn s disease Intravenous Date Approved June 2014 apremilast Otezla Celgene Psoriatic arthritis Oral recombinant factor IX Alprolix Biogen Hemophilia B Intravenous sodium hyaluronate solution Monovisc Anika Osteoarthritis Injection metreleptin Myalept Amylin Generalized lipodystrophy Subcutaneous elosulfase alfa Vimizim BioMarin Mucopolysaccharidosis (enzyme deficiency) glatiramer (three times/ week) Intravenous Copaxone 40 mg Teva Multiple sclerosis Subcutaneous treprostinil Orenitram United Therapeutics Pulmonary arterial catridecacog (Factor XIII, recombinant) Tretten Novo Nordisk Faxtor XIII deficiency Intravenous January 2014 Oral December 2014 December 2013 sofosbuvir Sovaldi Gilead Hepatitis C Oral December 2013 simeprevir Olysio Johnson & Johnson Hepatitis C Oral November 2013 riociguat Adempas Bayer Pulmonary arterial macitentan Opsumit Actelion Pulmonary arterial methotrexate Otrexup Antares Rheumatoid arthritis Subcutaneous recombinant coagulation factor VIII ferric carboxymaltose Novoeight NovoNordisk Hemophilia A Intravenous Injectafer American Regent Iron deficiency anemia Intravenous Oral October 2013 Oral October 2013 October 2013 October 2013 August 2013 dolutegravir Tivicay Viiv HIV Oral August 2013 tacrolimus extendedrelease BAX 326 (Factor IX, recombinant [rfix]) Advograf XL Astellas Immunosuppressant Oral July 2013 Rixubis Baxter Hemophilia B Intravenous July 2013

Drug Insights > Specialty Pipeline Update Page 3 New Indications for Approved Specialty Products Generic Name Brand Name Manufacturer New Indication Date Approved antihemophilic factor VIII Kogenate FS Bayer Routine prophylaxis in adults with Hemophilia A ecallantide Kalbitor Dyax Approved for patients 12 years and older with hereditary angioedema omalizumab Xolair Genentech Chronic idiopathic urticaria ivacaftor Kalydeco Vertex Gene mutations including: G178R, S549N, S549R, G551S, G1244E, S1251N, S1255P and G1349D anti-inhibitor coagulant complex Feiba Baxter Prophylactic treatment of hemophilia A or B January 2014 raltegravir Isentress Merck New formulation: pediatric oral suspension January 2014 tocilizumab Actemra Genentech New formulation: subcutaneous October 2013 20% subcutaneous immunoglobulin Hizentra CSL Behring Once every two week administration September 2013 certolizumab pegol Cimzia UCB Active psoriatic arthritis September 2013 ustekinumab Stelara Janssen Biotech (J&J) Psoriatic arthritis September 2013 golimumab Simponi Aria Johnson & Johnson Rheumatoid arthritis (intravenous ) new formulation July 2013

Drug Insights > Specialty Pipeline Update Page 4 Oncology Product Approvals in the Past Twelve Months mercaptopurine suspension Date Approved Purixan Nova Laboratories Acute lymphoblastic leukemia Oral ceritinib Zykadia Novartis Non-small cell lung cancer Oral ramucirumab Cyramza Lilly Advanced gastric cancer Intravenous obinutuzumab Gazyva Roche Chronic lymphocytic leukemia Intravenous November 2013 ibrutinib Imbruvica Johnson & Johnson Mantle cell lymphoma Oral November 2013 afatinib Gilotrif Boehringer Ingelheim Non-small cell lung cancer Oral July 2013 New Indications for Approved Oncology Drugs Generic Name Brand Name Manufacturer New Indication Date Approved panitumumab Vectibix Amgen Use in combination with FOLFOX as first-line treatment in patients with wild-type KRAS metastatic colorectal cancer omacetaxine mepesuccinate Synribo Teva Approved for home administration (chronic or accelerated chronic myeloid leukemia) ofatumumab Arzerra GlaxoSmithKline First-line therapy in patients with chronic lymphocytic leukemia ibrutinib Imbruvica Pharmacyclics Chronic lymphocytic leukemia trametinib Mekinist GlaxoSmithKline Used in combination with Tafinlar for metastatic melanoma January 2014 sorafenib Nexavar Novartis Metastatic, differentiated thyroid cancer November 2013 pertuzumab Perjeta Genentech Neoadjuvant breast cancer October 2013 paclitaxel Abraxane Celgene Pancreatic cancer September 2013

Drug Insights > Specialty Pipeline Update Page 5 Pipeline Watch corifollitropin alfa N/A Merck Fertility Subcutaneous recombinant human C1 esterase inhibitor dolutegravir, abacavir, lamuvidine Ruconest Santarus/Pharming Hereditary angioedema Intravenous Anticipated Approval Date* July 2014 July 2014 N/A Viiv HIV Oral August 2014 idelalisib N/A Gilead Indolent non-hodgkin's lymphoma and chronic lymphocytic leukemia belinostat Beleodaq Spectrum Peripheral T-cell lymphoma Intravenous Oral August 2014 August 2014 eliglustat Cerdelga Sanofi Gaucher s disease Oral August 2014 peginterferon beta-1a Plegridy Biogen Multiple sclerosis Subcutaneous immune globulin/ hyaluronidase HyQvia Baxter Primary immune deficiency Subcutaneous fluocinolone acetonide Iluvien Alimera Sciences/ psivida Diabetic macular edema tacrolimus Envarsus Veloxis Pharmaceuticals Immunosuppressant (kidney transplant) Intravitreal implant August 2014 September 2014 September 2014 Oral October 2014 olaparib N/A AstraZeneca Ovarian cancer Oral October 2014 cobicistat N/A Gilead HIV Oral October 2014 elvitegravir N/A Gilead HIV Oral October 2014 ledipasvir, sofosbuvir N/A Gilead Hepatitis C Oral October 2014 veruprevir, ritonavir, ombitasvir (one pill) + dasabuvir recombinant human parathyroid hromone pembrolizumab (MK-3475) N/A AbbVie Hepatitis C Oral October 2014 Natpara NPS Pharmaceuticals Hypoparathyroidism Intravenous N/A Merck Metastatic melanoma Intravenous October 2014 October 2014 * Anticipated approval dates are predictions made by Prime Therapeutics based on industry information. References 1. http://www.reuters.com/article/2014/06/01/us-health-cancer-fda-iduskbn0ec13w20140601 2. http://www.fiercepharma.com/press-releases/imbruvica-ibrutinib-significantly-improves-progression-free-survival-overal-0?utm_medium=nl&utm_ source=internal 3. http://www.fiercebiotech.com/story/fda-breaks-silence-biosimilars-long-awaited-proposal/2014-05-14 2992-B1 Prime Therapeutics LLC 06/14