Specialty Pipeline Monthly Update September 2018

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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® Amgen Skeletal-related events (SREs) in multiple January 2018 myeloma cysteamine bitartrate Procysbi Horizon Pharma Nephropathic cystinosis January 2018

phenylephrine/ketoralac Omidria® Omeros Pediatric intraoperative miosis and reduce December 2017 intraocular solution postoperative pain tofacitinib Xeljanz®/ Pfizer Psoriatic arthritis December 2017 Xeljanz® XR mepolizumab Nucala® GSK Eosinophilic granulomatosis with December 2017 polyangiitis ixekizumab Taltz® Lilly Active psoriatic arthritis December 2017

evolocumab Repatha® Amgen Prevention of heart attacks, strokes, December 2017 coronary revascularizations in patients with established cardiovascular disease vemurafenib Zelboraf® Roche Erdheim-Chester disease (ECD) with BRAF November 2017 V600 mutation eculizumab Soliris® Alexion Adult patients with generalized myasthenia October 2017 gravis (gMG) who are anti-acetylcholine receptor (AchR) antibody-positive

continued Specialty Pipeline Update: September 2018 Page 5

New indications for approved specialty products (continued)

Generic name Brand name Manufacturer New Indication(s) Date approved ustekinumab Stelara® Janssen Moderate to severe plaque psoriasis October 2017 who are candidates for phototherapy or systemic therapy in pediatric patients aged 12 and older golimumab Simponi® Aria Janssen Adults with active PsA or active ankylosing October 2017 spondylitis Immune globulin intravenous Privigen® CSL Behring Adults with CIDP to improve neuromuscular October 2017 [human], 10% liquid disability Specialty Pipeline Update: September 2018 Page 6

Oncology product approvals in the past twelve months Route of Generic name Brand name Manufacturer Indication(s) administration Date approved 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 (MF) or Sézary syndrome (SS), the most common types of cutaneous T-cell lymphoma, after at least one prior systemic therapy iobenguane I 131 Azedra™ Progenics Unresectable Intravenous August 2018 Pharmaceuticals’ pheochromocytoma or paraganglioma that have spread beyond the original tumor site and require systemic anticancer therapy ivosidenib Tibsovo™ Agios Pharmaceuticals IDH1 mutation r/r Acute myeloid Oral July 2018 leukemia (AML) 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 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) pemetrexed ready-to- Pemfexy™ Eagle NSCLC and malignant pleural Intravenous November 2017 dilute mesothelioma acalabrutinib Calquence™ AstraZeneca Relapsed or refractory (r/r) Oral October 2017 mantle cell lymphoma axicabtagene ciloleucel Yescarta™ Kite Pharma r/r large B-cell lymphoma Intravenous October 2017

abemaciclib Verzenio™ Eli Lilly Breast cancer Oral October 2017 Specialty Pipeline Update: September 2018 Page 7

New indications for approved oncology drugs

Generic name Brand name Manufacturer New Indication Date approved ibrutinib Imbruvica® Janssen/Abbvie Relapsed or refractory and treatment- September 2018 naive patients with 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 small lymphocytic lymphoma (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 Non-Hodgkin lymphoma that has relapsed May 2018 or is refractory after having at least two other kinds of treatment osimertinib Tagrisso® Aerie First-line treatment of patients with April 2018 Pharmaceuticals metastatic non-small cell lung cancer (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 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

continued Specialty Pipeline Update: September 2018 Page 8

New indications for approved oncology drugs (continued)

Generic name Brand name Manufacturer New Indication Date approved 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 1 year old or older that are 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, human February 2018 epidermal growth factor receptor 2 (HER2)- 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 Metastatic high-risk castration-sensitive February 2018 prostate cancer in combination with 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 epidermal growth factor receptor (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 Philadelphia chromosome-positive chronic January 2018 myelogenous leukemia (Ph+ CML) cabozantinib Cabometyx® Exelixis Advanced renal cell carcinoma (aRCC) January 2018

bevacizumab Avastin® Genentech Glioblastoma December 2017

obinutuzumab Gazyva® Genentech/Biogen Follicular lymphoma December 2017

sunitinib Sutent® Pfizer Adjuvant txt of adults at high risk of November 2017 recurrent RCC following kidney removal

continued Specialty Pipeline Update: September 2018 Page 9

New indications for approved oncology drugs (continued)

Generic name Brand name Manufacturer New Indication Date approved alectinib Alecensa® Roche First-line treatment of ALK+ locally November 2017 advanced/metastatic NSCLC fulvestrant Faslodex® AstraZeneca For use with abemaciclib for the treatment November 2017 of hormone receptor-positive (HR+), HER2- advanced or metastatic breast cancer (MBC) in women with disease progression after endocrine therapy dasatinib Sprycel® BMS Pediatric patients with Ph+ CML in chronic November 2017 phase brentuximab vedotin Adcetris® Seattle Genetics/ Cutaneous T-cell lymphoma November 2017 Takeda nivolumab Opdivo® BMS Hepatocellular carcinoma patients October 2017 previously treated with sorafenib pembrolizumab Keytruda® Merck Recurrent locally advanced or metastatic October 2017 gastric of gastroesophageal junction whose tumors express PD-L1 with disease progression on or after two or more prior lines of therapy

Biosimilar product approvals in the past twelve months Reference Route of Generic name Brand name product Manufacturer Indication(s) administration Month approved 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 infliximab-qbtx Ixifi™ Remicade® Pfizer Rheumatoid arthritis (RA), Intravenous December 2017 Crohn’s disease (CD), ulcerative colitis (UC), ankylosing spondylitis (AS), psoriatic arthritis (PsA) and plaque psoriasis (Ps) trastuzumab-dkst Ogivri™ Herceptin® Mylan/Biocon Breast and gastric cancer Intravenous December 2017 Specialty Pipeline Update: September 2018 Page 10

Specialty pipeline Route of Anticipated Generic name Brand name Manufacturer Indication(s) administration approval date* lorlatinib N/A Pfizer ALK+ NSCLC Oral August 2018

ALIS (amikacin liposome N/A Insmed Inc Non-tuberculous mycobacterial Inhaled September inhalation suspension) (NTM) lung disease caused by 2018 Mycobacterium avium complex dacomitinib N/A Pfizer and SFJ First-line treatment of patients with Oral September Pharmaceuticals locally advanced or metastatic non- 2018 small cell lung cancer (NSCLC) with EGFR-activating mutations duvelisib N/A Verastem Full approval for the treatment of Oral September and Infinity patients with relapsed/refractory 2018 Pharmaceuticals chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) and an accelerated approval for the treatment of patients with relapsed/ refractory follicular lymphoma inotersen Tegsedi™ Ionis hTTR amyloidosis Subcutaneous October 2018

cemiplimab N/A Sanofi/Regeneron Metastatic cutaneous squamous Intravenous October 2018 cell carcinoma larotrectinib N/A Loxo Oncology, Inc Locally advanced or metastatic Oral October 2018 solid tumors with neurotrophic tyrosine kinase receptor fusion- proteins, regardless of tissue origin gilteritinib N/A Astellas/Kotobuki FLT3+ r/r AML Oral November Pharmaceutica 2018 emapalumab N/A Bivitru AB Primary hemophagocytic Intravenous November lymphohistiocytosis (HLH) 2018 larotrectinib N/A Loxo Oncology Inc. Locally advanced or metastatic Oral November solid tumors with neurotrophic 2018 tyrosine kinase receptor fusion- proteins, regardless of tissue of origin amifampridine Firdapse™ Bio Marin Lambert Eaton myasthenic Oral November syndrome (LEMS) 2018 gilteritinib N/A Astellas Kotobuki FLT3+ r/r/ AML Oral November Pharmaceutica 2018 talazoparib N/A Pfizer Germline BRCA-mutated (gBRCAm), Oral December HER2-negative locally advanced or 2018 metastatic breast cancer midazolam N/A UCB and Proximagen Acute treatment of seizures Intranasal December 2018 calaspargase pegol N/A Shire ALL Intravenous December 2018 brexanolone N/A Sage Therapeutics Postpartum depression Intravenous December 2018 glasdegib N/A Pfizer AML in combination with cytarabine Oral December 2018 levodopa inhalation powder Inbrija™ Acorda Therapeutics As needed treatment of symptoms Inhaler January 2019 of ‘off’ period in Parkinson’s disease patients taking a carbidopa/ levodopa regimen

continued Specialty Pipeline Update: September 2018 Page 11

Specialty pipeline (continued)

Route of Anticipated Generic name Brand name Manufacturer Indication(s) administration approval date* 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 January 2019– sclerosis (SPMS) March 2019 apomorphine N/A Sunovion Off episodes associated with Oral sublingual January 2019 Parkinson’s disease film cladribine Mavenclad™ EMD Serono/Ivax Short-course treatment of relapsing Oral January 2019 multiple sclerosis caplacizumab Cablivi™ Sanofi Acquired thrombotic Intravenous/ February 2019 thrombocytopenic purpura subcutaneous ravulizumab N/A 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 trastuzumab and Enhanze Genetech/Halozyme HER2-positive breast cancer Subcutaneous March 2019 hyaluronidase Herceptin™ * Anticipated approval dates are predictions made by Prime Therapeutics based on industry information. Specialty Pipeline Update: September 2018 Page 12

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

Blood modifiers CHS-1701 (pegfilgrastim) N/A (Neulasta® Coherus BioScience Neutropenia Subcutaneous November 2018 biosimilar)

Autoimmune GP2017 (adalimumab) N/A (Humira Sandoz/Novartis RA, JIA, PsA, AS, CD, UC, Ps, Subcutaneous November 2018 biosimilar) hidradenitis suppurativa, and uveitis

IV Oncology SB3 (trastuzumab) Ontruzant™ Samsung Bioepis HER2-positive breast and Intravenous October 2018 (Herceptin® Co Ltd gastric cancers biosimilar) CT-P10 (rituximab) Truxima™ Celltrion and Teva 3 of the 8 indications of Intravenous November 2019 (Rituxan® Rituxan® biosimilar) CT-P6 (trastuzumab) N/A (Herceptin® Celltrion and Teva HER2-positive breast and Intravenous December 2018 biosimilar) gastric cancers * Anticipated approval dates are predictions made by Prime Therapeutics based on industry information. Specialty Pipeline Update: September 2018 Page 13

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 galcanezumab/Lilly Prevention of migraines/SC October 2018 Beta-blockers, $$ $$ None antidepressants, (with (with anticonvulsants Aimovig Aimovig and and Ajovy) Ajovy) Dupixent® (dupilumab) Asthma/SC October 2018 Xolair®Nucala® $$ $$ None Cinquair®Fasenra® Xarelto® (rivaroxaban)/Janssen Reduce CV events in CAD October 2018 Aspirin $$ $$ None or PAD/Oral

Drugs to be evaluated for Watch List siponimod Secondary progressive 1/2019– Novantrone TBD TBD None multiple sclerosis (SPMS)/ 3/2019 oral caplacizumab Cablivi® 2/6/2019 Plasma exchange and TBD TBD TBD corticosteroids *Notations: $ < $0.08 per member per month (PMPM), $$ = $0.08 – $0.39 PMPM, $$$ = $0.40 – $2.00 PMPM, $$$$ > $2.01 PMPM

continued Specialty Pipeline Update: September 2018 Page 14

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

Drugs evaluated for Watch list, do not meet criteria amikacin liposome inhalation NTM lung disease caused by MAC/inhale September Intravenous amikacin suspension (ALIS)/Insmed 2018 Hemlibra® (emicizumab-kxwh)/Roche Hemophilia A /subcutaneous October 2018 Adynovate® Afstyla® Eloctate® Jivi® Tegsedi™ (inotersen)/ Hereditary ATTR amyloidosis/SC weekly October 2018 Onpattro® Ionis & Akcea emapalumab/Biovitrum AB Primary hemophagocytic November Combination of chemotherapy, lymphohistiocytosis (HLH)/intravenous 2018 immunotherapy and steroids followed by hematopoietic stem cell transplant Firdapse™ (amifampridine)/ Lambert Eaton myasthenic syndrome November Pyridostigmine, Catalyst & BioMarin (LEMS)/oral 2018 potassium channel blockers, prednisone, IVIG solriamfetol/ Excessive sleepiness or obstructive December Xyrem® Jazz Pharmaceuticals sleep disorder or narcolepsy/oral 2018 Provigil® Nuvigil®

Continuous positive airway pressure midazolam/ Acute seizures /intranasal December Diastat® UCB and Proximagen 2018 ravulizumab (ALXN1210)/ Paroxysmal nocturnal February 2019 Soliris® Alexion Pharmaceuticals hemoglobinuria/IV Scenesse® (afamelanotide)/ Erythropoietic protoporphyria/ February 2019 Sun avoidance Clinuvel Pharmaceuticals SC implant Mavenclad™(cladribine)/ Relapsing MS/oral January 2019 Gilenya® EMD Serono Tecfidera® Aubagio® *Notations: $ < $0.08 per member per month (PMPM), $$ = $0.08 – $0.39 PMPM, $$$ = $0.40 – $2.00 PMPM, $$$$ > $2.01 PMPM

References 1. https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm618047.htm. 2. https://www.prnewswire.com/news-releases/dompe-receives-fda-approval-of-oxervate-eye-drops-cenegermin-bkbj-ophthalmic-solution-first-in-class-recombinant-human-nerve-growth-factor-with-potential-to-completely- heal-rare-neurotrophic-keratitis-300701377.html. 3. http://ir.akceatx.com/news-releases/news-release-details/akcea-and-ionis-receive-complete-response-letter-waylivra-fda. 4. https://www.biospace.com/article/releases/fda-issues-a-complete-response-letter-for-new-drug-application-for-dasotraline-for-the-treatment-of-adhd/. 5. https://www.genengnews.com/gen-news-highlights/fda-extends-pdufa-date-for-acordas-inbrija-3-days-after-company-loses-ampyra-appeal/81256235. 6. http://www.news.sanofi.us/2018-09-03-Cablivi-TM-caplacizumab-approved-in-Europe-for-adults-with-acquired-thrombotic-thrombocytopenic-purpura-aTTP. 7. https://www.gsk.com/en-gb/media/press-releases/gsk-receives-complete-response-letter-from-us-fda-for-use-of-mepolizumab-in-copd-patients/.