Specialty Pipeline Monthly Update

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Critical updates in an ever changing environment

December 2018

New drug information

●● Gamifant™ (emapalumab-lzsg): The Food and Drug Administration (FDA) approved Sobi Pharmaceuticals’ Gamifant for treatment of pediatric (newborn and older) and adult patients with primary hemophagocytic lymphohistiocytosis (HLH) who have refractory, recurrent or progressive disease or intolerance with conventional HLH therapy. HLH is rare, occurring in only 80 – 100 people in the United States each year.1 Gamifant is to be administered intravenously over one hour twice per week and continued until hematopoietic stem cell transplantation (HSCT) is performed or unacceptable toxicity occurs. Sobi plans to launch Gamifant in early 2019.2

●● Daurismo™ (glasdegib): The FDA approved Pfizer’s oral Daurismo in combination with intravenous low-dose cytarabine for treatment of newly diagnosed acute myeloid leukemia (AML) in adult patients who are ≥ 75 years old or who have comorbidities that preclude use of intensive induction chemotherapy. Daurismo has an annual wholesale acquisition cost (WAC) of $203,100.

●● Vitrakvi™ (larotrectinib): The FDA approved Loxo Oncology’s (a development partner of Bayer) tissue agnostic cancer oral medication, Vitrakvi, for treatment of adult and pediatric patients with solid tumors that:

→→ have a neurotrophic receptor tyrosine kinase (NTRK) gene fusion without a known acquired resistance mutation,

→→ are metastatic or where surgical resection is likely to result in severe morbidity, and

→→ have no satisfactory alternative treatments or that have progressed following treatment. The average annual wholesale acquisition cost (WAC) for an adult is $393,600. Sensitive and specific tests are needed to reliably detect NTRK gene fusions that are not commonly ordered in practice as Loxo estimates there are only 2,500 – 3,000 U.S. patients that harbor the NTRK gene fusion annually.3

●● Truxima™ (rituximab-abbs): The FDA approved Truxima, Celltrion and Teva’s biosimilar medication for Roche’s Rituxan®, for the treatment of adult patients with CD20-positive, B-cell non-Hodgkin’s lymphoma (NHL) to be used as a single agent or in combination with chemotherapy. This is the first FDA approved Rituxan biosimilar; the FDA is also reviewing Pfizer’s Rituxan biosimilar product, PF‑05280586, which may be approved in July 2019. Celltrion and Teva have not disclosed a price or launch date; however; depending on patent litigation, a Rituxan biosimilar may be able to launch in the first half of 2019.

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: December 2018 Page 2

New drug information (continued)

●● Xospata™ (gilteritinib): The FDA approved Astellas Pharmaceuticals’ oral Xospata for the treatment of adult patients who have relapsed or refractory acute myeloid leukemia (AML) with a FLT3 mutation. This mutation represents 30 – 40% of AML patients.4 The annual WAC is ~ $270,000.

●● Firdapse™ (amifampridine): The FDA approved Catalyst Pharmaceuticals’ oral Firdapse for treatment of Lambert-Eaton myasthenic syndrome (LEMS), a rare autoimmune disorder characterized by muscle weakness. There are only 400 known cases in the U.S.5 Catalyst plans to launch Firdapse in the first quarter of 2019 at an annual WAC of $375,000.6, 7

●● Herzuma® (trastuzumab-pkrb): Celltrion and Teva received FDA approval for Herzuma, a biosimilar to Genentech/Roche’s Herceptin® for the indication of HER2-positive breast cancer. Herceptin is also approved for HER2-positive gastric cancer, but Herzuma did not receive this indication. This is the second Herceptin biosimilar approval, Mylan and Biocon’s Ogivri® was approved in December 2017, but has not yet launched. Herceptin is anticipated to lose exclusivity in June 2019; however, launch plans have not been released for either of Ogivri or Herzuma.

New indications

●● Venclexta® (venetoclax) tablets: The FDA granted accelerated approval to Abbvie’s Venclexta for use in combination with azacitidine or decitabine or low-dose cytarabine for treatment of newly diagnosed acute myeloid leukemia (AML) in adult patients who are ≥ 75 years or older, or who have comorbidities that preclude use of intensive induction chemotherapy. Venclexta was originally approved for the treatment of chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL), with or without 17p deletion, who have received at least one prior therapy.

●● Novoeight® (recombinant anthemophilic factor): The FDA changed Novo Nordisk’s Novoeight’s indication from “control and prevention of bleeding episodes” to “on-demand treatment and control of bleeding episodes.”

●● Tecentriq® (atezolizumab): The FDA expanded Roche’s IV Tecentriq label to include use in combination with the Avastin® (bevacizumab), paclitaxel and carboplatin for the first-line treatment of patients with metastatic non-squamous non-small cell lung cancer (NSCLC) with no EGFR or ALK genomic tumor aberrations. Prior to this approval, Tecentriq was approved for metastatic NSCLC patients who have disease progression during or following platinum-containing chemotherapy; as well as certain patients with locally advanced or metastatic urothelial carcinoma.

●● Nplate® (romiplostim): The FDA expanded the indication for Amgen’s Nplate to include pediatric patients one year of age and older with immune thrombocytopenia (ITP) for at least six months who have had an insufficient response to corticosteroids, immunoglobulins, or splenectomy. Specialty Pipeline Update: December 2018 Page 3

December news

●● “The FDA Bone, Reproductive and Urologic Drugs Advisory Committee (BRUDAC) are to review data supporting the Biologics License Application (BLA) for Evenity™ (romosozumab) (Amgen and UCB) for the treatment of osteoporosis in postmenopausal women at high risk for fracture at a meeting on 15 January, 2019.”8

●● “Sage Therapeutics, Inc., a clinical-stage biopharmaceutical company developing novel medicines to treat life-altering central nervous system (CNS) disorders, announced that the FDA has extended the Prescription Drug User Fee Act (PDUFA) date for its Priority Review of the New Drug Application (NDA) for Zulresso™ (brexanolone) injection for the treatment of postpartum depression (PPD). The previously disclosed December 19, 2018 PDUFA goal date has been extended by a period of three months to March 19, 2019.”9

●● “Amarin made waves in September when it announced a topline win in the Reduce-It trial of its purified fish oil product Vascepa®. Full data, presented at the American Heart Association meeting in Chicago, added an impressive benefit on harder cardiovascular endpoints.”10

●● “AbbVie has struck a deal with Pfizer that requires Pfizer not to launch its Humira® biosimilar until November 2023. The date falls after biosimilar launch timelines for several other drug makers that have already made their own patent deals with AbbVie. The Pfizer deal marks the seventh time AbbVie has negotiated agreements with companies that delay the introduction of biosimilars for Humira, the company’s best-selling rheumatoid arthritis medicine.”11 Specialty Pipeline Update: December 2018 Page 4

Specialty new product approvals in the past twelve months Route of Generic name Brand name Manufacturer Indication(s) administration Month approved amifampridine Firdapse™ Catalyst Lambert-Eaton myasthenic Oral November 2018 Pharmaceuticals syndrome (LEMS) emapalumab-lzsg Gamifant™ Novimmune Hemophagocytic Intravenous November 2018 lymphohistiocytosis (HLH) elapegademase-lvlr Revcovi™ Leadiant Adenosine deaminase severe Intramuscular October 2018 Pharmaceuticals combined immune deficiency (ADA-SCID) inotersen Tegsedi™ Ionis Hereditary transthyretin- Subcutaneous October 2018 Pharmaceuticals/ mediated amyloidosis (hATTR) Akcea amikacin liposome inhalation Arikayce™ Insmed Mycobacterium avium complex Inhalation September 2018 suspension (MAC) lung disease antihemophilia factor Jivi™ Bayer Hemophilia A Intravenous September 2018 [recombinant] PEGylated-aucl riluzole Tiglutik™ ITF Pharma Amyotrophic lateral sclerosis Oral September 2018 (ALS) cenegermin-bkbj Oxervate™ Dompe farmaceutici Neurotrophic keratitis Eye drop August 2018 SpA lanadelumab-flyo Takhzyro™ Shire Prevention of hereditary Subcutaneous August 2018 angioedema stiripentol Diacomit™ Biocodex In combination with clobazam Oral August 2018 for Dravet syndrome (specialty status pending pricing and distribution information) migalastat Galafold™ Amicus Fabry disease with an amenable Oral August 2018 Therapeutics GLA variant patisiran Onpattro™ Alnylam Polyneuropathy caused by Intravenous August 2018 hATTR lusutrombopag Mulpleta™ Shionogi Thrombocytopenia in chronic Oral August 2018 liver disease who are scheduled to undergo a procedure immune globulin intravenous, Panzyga® Octapharma Primary humoral IV August 2018 human - ifas immunodeficiency (PI) and chronic immune thrombocytopenia (ITP) 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

continued Specialty Pipeline Update: December 2018 Page 5

Specialty new product approvals in the past twelve months (continued)

Route of Generic name Brand name Manufacturer Indication(s) administration Month approved 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 Specialty Pipeline Update: December 2018 Page 6

New indications for approved specialty products

Generic name Brand name Manufacturer New indication(s) Date approved romiplostim Nplate™ Amgen Pediatric patients one year of age and older with December 2018 chronic ITP recombinant anthemophilic Novoeight® Novo Nordisk On-demand treatment and control of bleeding episodes November 2018 factor eltrombopag Promacta® Novartis In combination with standard immunosuppressive November 2018 therapy for first-line treatment of severe aplastic anemia (SAA) sodium oxybate oral Xyrem® Jazz To treat cataplexy and excessive daytime sleepiness October 2018 solution Pharmaceuticals (EDS) in pediatric narcolepsy patients alirocumab Praluent® Regeneron In combination with apheresis in treatment of October 2018 heterozygous hypercholesterolemia (HeFH) for clinical ASCVD, who require additional LDL cholesterol lowering rituximab Rituxan® Genentech Microscopic polyangiitis and granulomatosis with October 2018 polyangiitis dupilumab Dupixent® Sanofi/Regeneron Add-on maintenance treatment for patients aged October 2018 12 years and older who have eosinophilic phenotype or oral corticosteroid-dependent moderate to severe asthma emicizumab-kxwh Hemlibra® Roche Hemophilia A without factor VIII inhibitors October 2018

tocilizumab Actemra® Genentech Subcutaneous formulation approved in patients age 2 September 2018 and older with active systemic juvenile idiopathic arthritis riluzole Tiglutik™ ITF Pharma Amyotrophic lateral sclerosis (ALS) September 2018

aflibercept Eylea® Regeneron Wet age-related macular degeneration August 2018

lumacaftor/ivacaftor Orkambi® Vertex Children ages 2–5 who have two copies of the August 2018 Pharmaceuticals F508del-CFTR mutation ivacaftor Kalydeco® Vertex Pediatric patients aged 12 months to younger than August 2018 Pharmaceuticals two years old with cystic fibrosis who have at least one mutation in the CFTR gene incobotulinumtoxinA Xeomin® Merck Excessive drooling July 2018

C1 esterase inhibitor Cinryze® Shire Pediatric patients with hereditary angioedema (HAE) July 2018 [human] methoxy polyethylene Mircera® Roche Pediatric patients aged 5 to 17 years of age on June 2018 glycol-epoetin beta hemodialysis who are switching from another erythropoiesis-stimulating agent (ESA) following hemoglobin stabilization with an ESA rituximab Rituxan® Genentech Pemphigus vulgaris June 2018

tofacitinib citrate Xeljanz® Pfizer Ulcerative colitis June 2018

certolizumab pegol Cimzia® UCB Plaque Psoriasis June 2018

denosumab Prolia® Amgen Glucocorticoid-induced osteoporosis May 2018

tocilizumab Actemra® Genentech Subcutaneous formulation to treat polyarticular juvenile May 2018 idiopathic arthritis (IV previously approved) fingolimod Gilenya® Novartis Multiple sclerosis in children and adolescents age May 2018 10 years and older von Willebrand factor Vonvendi® Shire Perioperative management of bleeding in adult patients April 2018 (recombinant) with von Willebrand disease sargramostim Leukine® Sanofi-Aventis Hematopoietic syndrome of acute radiation syndrome April 2018 Specialty Pipeline Update: December 2018 Page 7

New indications for approved specialty products (continued)

Generic name Brand name Manufacturer New indication(s) Date approved Immune globulin Hizentra® CSL Behring Maintenance therapy in adults with chronic March 2018 subcutaneous (human), inflammatory demyelinating polyneuropathy 20% liquid ferumoxytol injection Feraheme® AMAG Iron deficiency anemia intolerant or non-responsive February 2018 to oral iron therapy somatropin Zomacton® Ferring Adults with growth hormone deficiency February 2018 Pharmaceuticals plecanatide Trulance® Synergy Irritable bowel syndrome (IBS) February 2018

denosumab Xgeva® Amgen Skeletal-related events in multiple myeloma January 2018

cysteamine bitartrate Procysbi® Horizon Pharma Nephropathic cystinosis January 2018 Specialty Pipeline Update: December 2018 Page 8

Oncology product approvals in the past twelve months Route of Generic name Brand name Manufacturer Indication(s) administration Date approved gilteritinib Xospata™ Astellas Relapsed or refractory (r/r) Oral November 2018 acute myeloid leukemia (AML) larotrectinib Vitrakvi™ Loxo Oncology Solid tumors — with NTRK Oral November 2018 gene fusion glasdegib Daurismo™ Pfizer™ AML patients ≥ 75 years old Oral November 2018

lorlatinib Lorbrena™ Pfizer Metastatic non-small cell lung Oral November 2018 cancer (NSCLC) talazoparib Talzenna™ Pfizer Locally advanced or metastatic Oral October 2018 breast cancer cemiplimab-rwlc Libtayo™ Regeneron Metastatic cutaneous Intravenous September 2018 Pharmaceuticals squamous cell carcinoma (CSCC) dacomitinib Vizimpro™ Pfizer Metastatic NSCLC Oral September 2018

duvelisib Copiktra™ Verastem and Infinity Chronic lymphocytic leukemia Oral September 2018 Pharmaceuticals (CLL) or small lymphocytic lymphoma (SLL) moxetumomab Lumoxiti™ AstraZeneca/ Relapsed or refractory hairy cell Intravenous September 2018 pasudotox-tdfk MedImmune leukemia mogamulizumab-kpkc Poteligeo™ Kyowa Kirin Relapsed or refractory mycosis Intravenous August 2018 fungoides or Sézary syndrome after at least one prior systemic therapy iobenguane I 131 Azedra™ Progenics Pheochromocytoma or Intravenous August 2018 Pharmaceuticals’ paraganglioma that is unresectable, has spread beyond the original tumor site and requires systemic anticancer therapy ivosidenib Tibsovo™ Agios Pharmaceuticals IDH1 mutation r/r AML Oral July 2018

binimetinib Mektovi™ Array BioPHarma BRAF V600E or V600K mutation Oral July 2018 metastatic melanoma encorafenib Braftovi™ Array BioPharma BRAF V600E or V600K mutation Oral July 2018 metastatic melanoma abiraterone acetate Yonsa™ Churchill M-CRPC Oral May 2018 Pharmaceuticals apalutamide Erleada™ Janssen Non-metastatic castration- Oral February 2018 resistant prostate cancer (NM-CRPC) lutetium Lu 177 dotatate Lutathera™ Advanced Accelerator Gastroenteropancreatic Intravenous February 2018 Applications neuroendocrine tumors (GEP‑NETs) Specialty Pipeline Update: December 2018 Page 9

New indications for approved oncology drugs

Generic name Brand name Manufacturer New Indication Date approved atezolizumab Tecentriq® Roche In combination with Avastin®, paclitaxel December 2018 and carboplatin for first-line treatment of NSCLC venetoclax Venclexta® Abbvie In combination with azacitidine or November 2018 decitabine or low-dose cytarabine for treatment of newly-diagnosed AML in adult patients who are ≥ 75 years old or who have comorbidities that preclude use of intensive induction chemotherapy brentuximab vedotin Adcetris® Seattle Genetics In combination with chemotherapy for November 2018 certain adults with peripheral T-cell lymphomas (PTCL) in the first-line setting ibrutinib Imbruvica® Janssen/Abbvie r/r and treatment-naive patients with September 2018 Waldenstrom’s macroglobulinemia nivolumab Opdivo® BMS Metastatic small cell lung cancer (SCLC) August 2018

lenvatinib Lenvima® Eisai Hepatocellular carcinoma August 2018

ribociclib Kisqali® Novartis In combination with fulvestrant for the July 2018 treatment of postmenopausal women with HR-positive, HER2-negative advanced or metastatic breast cancer, as initial endocrine based therapy or following disease progression on endocrine therapy ribociclib Kisqali® Novartis HR-positive, HER2-negative advanced or July 2018 metastatic breast cancer enzalutamide Xtandi® Astellas NM-CRPC July 2018

nivolumab + ipilimumab Opdivo® + Yervoy® BMS Microsatellite instability-high or mismatch July 2018 repair-deficient metastatic colorectal cancer pembrolizumab Keytruda® Merck r/r primary mediastinal B-cell lymphoma July 2018 (PMBCL) pembrolizumab Keytruda® Merck Recurrent or metastatic cervical cancer June 2018 with disease progression on or after chemotherapy whose tumors express PD-L1 ventoclax Venclexta® AbbVie/Roche Accelerated approval to full approval: Used June 2018 in combination with rituximab or alone for patients with CLL or SLL, with or without 17p deletion, who have tried at least one therapy dabrafenib + trametinib Tafinlar® + Mekinist® Novartis Administered together as adjuvant May 2018 treatment with melanoma with BRAF V600E and V600K mutations and BRAF V600E mutation-positive unresectable or metastatic anaplastic thyroid cancer tisagenlecleucel Kymriah® Novartis r/r non-Hodgkin lymphoma after having May 2018 at least two other kinds of treatment osimertinib Tagrisso® Aerie First-line treatment of patients with April 2018 Pharmaceuticals metastatic NSCLC whose tumors have epidermal growth factor receptor (EGFR) exon 19 deletions or exon 21 L858R mutations nivolumab + ipilimumab Opdivo® + Yervoy® BMS Intermediate or poor risk, previously April 2018 untreated advanced renal cell carcinoma

continued Specialty Pipeline Update: December 2018 Page 10

New indications for approved oncology drugs (continued)

Generic name Brand name Manufacturer New Indication Date approved rucaparib Rubraca® Clovis Oncology Maintenance treatment of recurrent April 2018 epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in a complete or partial response to platinum- based chemotherapy blinatumomab Blincyto® Amgen B-cell precursor acute lymphoblastic April 2018 leukemia (ALL) who are in first or second complete remission with minimal residual disease (MRD) greater than or equal to 0.1% nilotinib Tasigna® Novartis Newly diagnosed Philadelphia April 2018 chromosome-positive (Ph+) chronic myeloid leukemia (CML) in pediatric patients one year or older that is in chronic phase (Ph+ CML-CP) or Ph+ CML-CP resistant or intolerant to prior tyrosine- kinase inhibitor (TKI) therapy brentuximab vedotin Adcetris® Seattle Genetics Previously untreated stage III or IV classical April 2018 Hodgkin lymphoma abemaciclib Verzenio® Eli Lilly Hormone receptor (HR)-positive, HER2- February 2018 negative advanced or metastatic breast cancer durvalumab Imfinzi® AstraZeneca Locally advanced, stage 3, unresectable February 2018 NSCLC that has not following platinum- based chemoradiation abiraterone acetate Zytiga® J & J High risk M-CSPC in combination with February 2018 prednisone nivolumab Opdivo® BMS Melanoma patients who are at high risk February 2018 of disease recurrence following complete surgical resection afatinib Gilotrif ® Boehringer Ingelheim First-line treatment of patients with January 2018 metastatic NSCLC with non-resistant EGFR mutations arsenic trioxide Trisenox® Teva In combination with tretinoin in adult January 2018 patients with newly-diagnosed low-risk acute promyelocytic leukemia (APL) olaparib Lynparza® AstraZeneca/Merck Deleterious or suspected deleterious January 2018 gBRCAm, HER2-negative metastatic breast cancer who have previously been treated with chemotherapy in the neoadjuvant, adjuvant, or metastatic setting pertuzumab Perjeta® Genentech In combination with Herceptin® and January 2018 chemotherapy for adjuvant treatment of HER2-positive early breast cancer at high risk of recurrence bosutinib Bosulif ® Pfizer Ph+ CML January 2018

cabozantinib Cabometyx® Exelixis Advanced renal cell carcinoma January 2018 Specialty Pipeline Update: December 2018 Page 11

Biosimilar product approvals in the past twelve months Reference Route of Generic name Brand name product Manufacturer Indication(s) administration Month approved trastuzumab-pkrb Herzuma® Herceptin® Celltrion and HER2-positive breast cancer Intravenous December 2018 Teva rituximab-abbs Truxima™ Rituxan® Celltrion and NHL Intravenous November 2018 Teva pegfilgrastim-cbqv Udenyca™ Neulasta® Coherus Neutropenia Subcutaneous November 2018 BioSciences adalimumab-adaz Hyrimoz™ Humira® Sandoz/ Autoimmune Subcutaneous October 2018 Novartis filgrastim-aafi Nivestym™ Neupogen® Pfizer Neutropenia Intravenous/ July 2018 subcutaneous pegfilgrastim-jmdb Fulphila™ Neulasta® Mylan/Biocon Neutropenia Subcutaneous June 2018

epotin alfa-epbx Retacrit® Procrit®/ Pfizer/Hospira Anemia Intravenous/ May 2018 Epogen® subcutaneous Specialty Pipeline Update: December 2018 Page 12

Specialty pipeline Route of Anticipated Generic name Brand name Manufacturer Indication(s) administration approval date* midazolam Nayzilam™ UCB and Proximagen Acute treatment of seizures Intranasal December 2018

calaspargase pegol N/A Shire ALL Intravenous December 2018

levodopa inhalation powder Inbrija™ Acorda Therapeutics Off episodes associated with Inhaler January 2019 Parkinson’s disease sacituzumab govitecan N/A Immunomedics Metastatic triple-negative breast Intravenous January 2019 cancer (mTNBC) who previously received at least two prior therapies for metastatic disease siponimod N/A Novartis Secondary progressive multiple Oral 1Q2019 sclerosis (SPMS) apomorphine N/A Sunovion Off episodes associated with Oral sublingual January 2019 Parkinson’s disease film romosozumab Evenity™ Amgen/UCB Osteoporosis Subcutaneous January 2019

cladribine Mavenclad™ EMD Serono/Ivax Short-course treatment of relapsing Oral TBD multiple sclerosis caplacizumab Cablivi™ Sanofi Acquired thrombotic Intravenous/ February 2019 thrombocytopenic purpura subcutaneous ravulizumab Ultomiris™ Alexion Paroxysmal nocturnal Intravenous February 2019 hemoglobinuria tagraxofusp Elzonris™ Stemline Blastic plasmacytoid dendritic cell Intravenous February 2019 Therapeutics neoplasm afamelanotide Scenesse® Clinuvel Erythropoietic protoporphyria Subcutaneous February 2019 Pharmaceuticals recombinant turoctocog alfa N/A Novo Nordisk Hemophilia A Intravenous February 2019 pegol trastuzumab and Enhanze Genetech/Halozyme HER2-positive breast cancer Subcutaneous March 2019 hyaluronidase Herceptin™ infusion risankizumab N/A AbbVie Plaque psoriasis Subcutaneous April 2019

immune globulin N/A ADMA Biologics Primary immune deficiency disease Intravenous April 2019 (PIDD) selinexor N/A Karyopharm Penta-refractory MM Oral April 2019

erdafitinib N/A Janssen Urothelial cancer Oral May 2019

quizartinib N/A Daiichi Sankyo AML Oral May 2019

onasemnogene abeparvovec Zolgensma® Novartis Spinal muscular atrophy Type 1 Intravenous May 2019 (SMA1) riluzole Nurtec™ Biohaven ALS SL orally July 2019 disintegrating tablet *Anticipated approval dates are predictions made by Prime Therapeutics based on industry information. Specialty Pipeline Update: December 2018 Page 13

Biosimilar pipeline Route of Anticipated Generic name Brand name Manufacturer Indication(s) administration approval date*

Autoimmune GP2017 (adalimumab) N/A (Humira® Sandoz/Novartis Autoimmune Subcutaneous November 2018 biosimilar) SB5 (adalimumab) N/A (Humira® Samsung Bioepis Autoimmune Subcutaneous July 2019 biosimilar)

IV Oncology SB3 (trastuzumab) Ontruzant™ Samsung Bioepis HER2-positive breast cancer Intravenous October 2018 (Herceptin® Co Ltd biosimilar) PF-05280014 (trastuzumab) N/A (Herceptin® Pfizer HER2-positive breast cancer Intravenous May 2019 biosimilar) PF-0643935 (bevacizumab) N/A (Avastin® Pfizer NSCLC Intravenous June 2019 biosimilar) PF-05280586 N/A (Rituxan® Pfizer NHL Intravenous July 2019 biosimilar) *Anticipated approval dates are predictions made by Prime Therapeutics based on industry information. Specialty Pipeline Update: December 2018 Page 14

Watch list Criteria for inclusion on the Watch List include: drug is submitted to the FDA and is anticipated to have material impact to trend and/or material impact to preferred product strategies (medical or pharmacy). Net new Net new impact to impact to Anticipated PMPM* PMPM* Proposed indication/ approval Similar pharmacy medical Brand (generic)/manufacturer route of administration (PDUFA date) products Spend* benefit benefit esketamine/Janssen Treatment-resistant March 2019 IV ketamine (off-label) $$ $$ depression Symyax® Zolgensma® (onasemnogene SMA1 May 2019 Spinraza® $$ to $$ to abeparvovec or AVXS-101) $$$ $$$ Novartis

Drugs to be evaluated for Watch List Vascepa® (icosapent ethyl)/Amarin CV risk reduction/Oral TBD OTC fish oil products TBD TBD None

Proposed indication/ Anticipated approval Brand (generic)/manufacturer route of administration (PDUFA date) Similar products

Drugs evaluated for Watch list, do not meet criteria solriamfetol/Jazz Pharmaceuticals Excessive sleepiness associated with December 2018 Xyrem® narcolepsy or obstructive sleep apnea/Oral Provigil® Nuvigil® Continuous positive airway pressure Nayzilam™ (midazolam) UCB and Acute seizures/Intranasal December 2018 Diastat® Proximagen Mavenclad™ (cladribine)/ Relapsing MS/Oral 1Q2019 Gilenya® EMD Serono Tecfidera® Aubagio® siponimod/Novartis Secondary progressive multiple sclerosis January 2019 Novantrone® (SPMS) Ultomiris™ (ravulizumab)/ Paroxysmal nocturnal hemoglobinuria/IV February 2019 Soliris® Alexion Pharmaceuticals Scenesse® (afamelanotide)/ Erythropoietic protoporphyria/SC implant February 2019 Sun avoidance Clinuvel Pharmaceuticals Cablivi™ (caplacizumab)/Sanofi Acquired thrombotic thrombocytopenic February 2019 Daily plasma exchange purpura and corticosteroids for immunosuppression *Notations: $ < $0.08 per member per month (PMPM), $$ = $0.08 – $0.39 PMPM, $$$ = $0.40 – $2.00 PMPM, $$$$ > $2.01 PMPM

References 1 http://www.evaluate.com/vantage/articles/events/conferences/ash-2018-sobi-still-has-mountain-climb-gamifant. 2 https://www.biospace.com/article/sobi-and-novimmune-s-gamifant-gets-thumbs-up-for-ultra-rare-disease/. 3 https://www.forbes.com/sites/matthewherper/2018/11/26/loxo-and-bayers-amazing-drug-has-an-expensive-price/#4a9bcdca24d0. 4 https://www.biospace.com/article/releases/xospata-gilteritinib-approved-by-u-s-fda-for-adult-patients-with-relapsed-refractory-acute-myeloid-leukemia-aml-with-a-flt3-mutation/. 5 https://rarediseases.org/rare-diseases/lambert-eaton-myasthenic-syndrome/. 6 https://ir.catalystpharma.com/news-releases/news-release-details/fda-approves-firdapser-amifampridine-treatment-lambert-eaton. 7 https://www.biocentury.com/bc-extra/politics-policy/2018-12-14/firdapse-re-catalyzes-pricing-debate. 8 https://spinalnewsinternational.com/fda-evenity-osteoporosis-women/. 9 https://www.businesswire.com/news/home/20181120005168/en/Sage-Therapeutics-Receives-Notification-PDUFA-Extension-ZULRESSO%E2%84%A2. 10 http://www.evaluate.com/vantage/articles/events/conferences/aha-2018-amarin-goes-hard-vascepa-questions-remain. 11 https://www.fiercepharma.com/pharma/abbvie-inks-humira-patent-deal-no-7-delaying-pfizer-s-u-s-biosim-launch-until-late-2023.