Specialty Pipeline Monthly Update

Critical updates in an ever changing environment

March 2019

New drug information

●● Herceptin Hylecta™ (trastuzumab and hyaluronidase-oysk): The Food and Drug Administration (FDA) approved Herceptin Hylecta for the treatment of HER2-overexpressing breast cancer. It is a combination of Genentech’s Herceptin® and Halozyme Therapeutics hyaluronidase which helps deliver Herceptin Hylecta subcutaneously. Herceptin is administered as a maintenance dose intravenously over 30 minutes, Herceptin Hylecta is administered subcutaneously over 2 – 5 minutes. Genentech’s launch plans are pending. As reported in the prescribing information patient experience section, the subcutaneous formulation was preferred over the intravenous formulation by 86% of patients with the most common reason due to the lesser time requirement. Those who preferred the intravenous formulation (13%) reported fewer local injection reactions as the most common reason, 1% had no preference for the route of administration.

●● Trazimera™ (trastuzumab-qyyp): Pfizer received FDA approval for Trazimera, a biosimilar to Genentech’s Herceptin (trastuzumab), for the treatment of HER2-overexpressing breast cancer and HER2 overexpressing metastatic gastric or gastroesophageal junction adenocarcinoma. Trazimera is the fourth Herceptin biosimilar approved by the FDA. Herceptin is set to lose exclusivity in June 2019; however, no launch plans of any of the approved biosimilars have been announced.

●● Spravato™ (esketamine): Janssen received FDA approval for Spravato nasal spray in combination with an oral antidepressant for the treatment of treatment-resistant depression (TRD) in adults. The FDA considers patients to have treatment-resistant depression if they have major depressive disorder and, despite at least two trials of antidepressants, have not responded to treatment. The wholesale acquisition cost (WAC) of Spravato can be up to $6,785 for the first month of therapy depending on dose, and can run up to $3,540 per month thereafter.1 Spravato will only be available through a restricted distribution system under a Risk Evaluation and Mitigation Strategy (REMS) due to safety concerns (i.e., sedation, dissociation, abuse and misuse). Spravato is self-administered under the supervision of a health care provider and the patient must be observed for at least two hours until the patient is safe to leave.

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: March 2019 Page 2

New indications

●● Keytruda® (pembrolizumab): Merck’s Keytruda received FDA approval for the adjuvant treatment of melanoma patients with lymph node involvement following complete resection. Keytruda is also FDA approved for certain forms of cancer including: non-small cell lung, head and neck squamous cell, classical Hodgkin’s lymphoma, primary mediastinal large B-cell lymphoma, urothelial carcinoma, microsatellite instability-high, gastric, cervical, hepatocellular carcinoma and Merkel cell carcinoma.

●● Tecentriq® (atezolizumab): Genentech’s Tecentriq received FDA accelerated approval in combination with Celegene’s Abraxane® (nab-paclitaxel) chemotherapy for first-line treatment of unresectable locally advanced or metastatic triple-negative breast cancer (TNBC) that expresses PD-L1. Tecentriq is also approved for certain forms of urothelial carcinoma and non-small cell lung cancer.

●● Dupixent® (dupilumab): Sanofi/Regeneron received FDA approval to expand the indication of Dupixent’s atopic dermatitis indication to include patients aged 12 – 17 years of age.

●● Losurf® (trifluridine/tipiracil): Losurf from Taiho Pharmaceuticals received a new indication for the treatment of adult patients with metastatic gastric or gastroesophageal junction adenocarcinoma previously treated with at least two prior lines of chemotherapy that included a fluoropyrimidine, a platinum, either a taxane or irinotecan, and if appropriate, HER2/neu-targeted therapy. Losurf is also approved for metastatic colorectal cancer previously treated with fluoropyrimidine-, oxaliplatin- and irinotecan-based chemotherapy, an anti-VEGF biological therapy, and if RAS wild-type, an anti-EGFR therapy. March news

●● “Pfizer’s rheumatoid arthritis med Xeljanz®, which already bears a black-box warning, has run into cardiovascular safety problems with a higher dose in clinical trials. But whether those safety troubles belong to the entire class of JAK inhibitors remains to be seen.”2

●● “Alkermes plc and Biogen Inc. announced that the FDA has accepted for review the New Drug Application (NDA) for diroximel fumarate (BIIB098), a novel oral fumarate in development for the treatment of relapsing forms of multiple sclerosis (MS). The NDA has been assigned a PDUFA (Prescription Drug User Fee Act) target action date in the fourth quarter of 2019. If approved, Biogen intends to market diroximel fumarate under the brand name VUMERITY™, which has been conditionally accepted by the FDA and will be confirmed upon approval.”3

●● “Eli Lilly has a battle on its hands in the migraine prevention category with third-to-market CGRP inhibitor Emgality® but could get a leg-up with an indication in episodic cluster headache.”4

●● “Regeneron and Sanofi announced that the FDA has accepted for Priority Review the supplemental Biologics License Application (sBLA) for Dupixent® (dupilumab) as an add-on maintenance treatment for adults with inadequately controlled severe chronic rhinosinusitis with nasal polyps (CRSwNP).”5 Specialty Pipeline Update: March 2019 Page 3

Specialty new product approvals in the past twelve months Route of Month Generic name Brand name Manufacturer Indication(s) administration approved esketamine Spravato™ Janssen Treatment-resistant depression Nasal spray March 2019

Antihemophilic factor Esperoct™ Novo Nordisk Hemophilia A IV February 2019 (recombinant), glycopegylated-exei caplacizumab-yhdp Cablivi™ Sanofi Acquired thrombotic IV/SC December 2018 thrombocytopenic purpura monomethyl fumarate delayed- Bafiertam™ Banner Life Science Relapsing multiple sclerosis Oral December 2018 release (tentative approval) immune globulin subcutaneous Cutaquig™ Octapharma Primary humoral SC December 2018 [human]-hipp immunodeficiency levodopa Inbrija™ Accorda OFF episodes in Parkinson’s Inhalation December 2018 Therapeutics disease ravulizumab-cwvz Ultromiris™ Alexion Paroxysmal nocturnal IV December 2018 Pharmaceuticals hemoglobinuria amifampridine Firdapse™ Catalyst Lambert-Eaton myasthenic Oral November 2018 Pharmaceuticals syndrome (LEMS) emapalumab-lzsg Gamifant™ Novimmune Hemophagocytic IV November 2018 lymphohistiocytosis (HLH) elapegademase-lvlr Revcovi™ Leadiant Adenosine deaminase severe IM October 2018 Pharmaceuticals combined immune deficiency (ADA-SCID) inotersen Tegsedi™ Ionis Polyneuropathy of hereditary SC October 2018 Pharmaceuticals/ transthyretin-mediated Akcea amyloidosis (hATTR) amikacin liposome Arikayce™ Insmed Mycobacterium avium complex Inhalation September 2018 (MAC) lung disease antihemophilia factor Jivi™ Bayer Hemophilia A IV September 2018 [recombinant] PEGylated-aucl riluzole Tiglutik™ ITF Pharma Amyotrophic lateral sclerosis Oral September 2018 (ALS) cenegermin-bkbj Oxervate™ Dompe Neurotrophic keratitis Eye drop August 2018 farmaceutici SpA lanadelumab-flyo Takhzyro™ Shire Prevention of hereditary SC 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 of hATTR IV August 2018

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)

continued Specialty Pipeline Update: March 2019 Page 4

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

Route of Month Generic name Brand name Manufacturer Indication(s) administration approved cannabidiol Epidiolex® GW Lennox-Gastaut syndrome and Oral July 2018 Pharmaceuticals Dravet syndrome baricitinib Olumiant® Lilly/Incyte Rheumatoid arthritis Oral June 2018

pegvaliase-pqpz Palyniziq™ BioMarin Phenylketonuria SC 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 ITP Oral April 2018 hexahydrate burosumab-twza Crysvita® Ultragenyx and X-linked hypophosphatemia SC April 2018 Kyowa Kirin tildrakizumab-asmn Ilumya® Sun Pharmaceutical Plaque psoriasis SC April 2018

New indications for approved specialty products

Generic name Brand name Manufacturer New Indication(s) Date approved dupilumab Dupixent® Sanofi/Regeneron Expand atopic dermatitis indication to patients aged March 2019 12 – 17 years of age tacrolimus extended-release Envarsus XR® Veloxis Prophylaxis of organ rejection in kidney transplant December 2018

romiplostim Nplate® Amgen Pediatric patients 1 year of age and older with December 2018 chronic ITP recombinant antihemophilic Novoeight® Novo Nordisk On-demand treatment and control of bleeding November 2018 factor episodes in hemophilia A eltrombopag Promacta® Novartis First-line treatment of severe aplastic anemia (SAA) November 2018

sodium oxybate oral solution Xyrem® Jazz Pediatric narcolepsy patients October 2018 Pharmaceuticals 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 September 2018 age 2 and older with active systemic juvenile idiopathic arthritis riluzole Tiglutik™ ITF Pharma ALS September 2018

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

lumacaftor/ivacaftor Orkambi® Vertex Children ages 2 – 5 who have 2 copies of the August 2018 Pharmaceuticals F508del-CFTR mutation

continued Specialty Pipeline Update: March 2019 Page 5

New indications for approved specialty products (continued)

Generic name Brand name Manufacturer New Indication(s) Date approved ivacaftor Kalydeco® Vertex Pediatric patients aged 12 months to younger than August 2018 Pharmaceuticals 2 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 [human] Cinryze® Shire Pediatric patients with hereditary angioedema (HAE) July 2018

methoxy polyethylene Mircera® Roche Pediatric patients aged 5 – 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 SC 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 April 2018 (recombinant) patients with von Willebrand disease sargramostim Leukine® Sanofi-Aventis Hematopoietic syndrome of acute radiation April 2018 syndrome

Oncology product approvals in the past twelve months Route of Date Generic name Brand name Manufacturer Indication(s) administration approved trastuzumab and Herceptin Genentech/ HER2-overexpressing SC infusion February 2019 hyaluronidase-oysk Hylecta™ Halozyme breast cancer calaspargase pegol-mknl Asparlas™ Shire Acute lymphoblastic leukemia IV December 2018 (ALL) tagraxofusp-erzs Elzonris™ Stemline Blastic plasmacytoid dendritic IV December 2018 Therapeutics cell neoplasm gilteritinib Xospata™ Astellas relapsed or refractory (r/r) acute Oral November 2018 myeloid leukemia (aml) larotrectinib Vitrakvi™ Loxo Solid tumors with NTRK gene Oral November 2018 Oncology 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)

continued Specialty Pipeline Update: March 2019 Page 6

Oncology product approvals in the past twelve months (continued)

Route of Date Generic name Brand name Manufacturer Indication(s) administration approved 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 Intravenous September 2018 pasudotox-tdfk MedImmune hairy cell 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 IDH1 mutation r/r AML Oral July 2018 Pharmaceuticals binimetinib Mektovi™ Array BioPHarma BRAF V600E or V600K mutation Oral July 2018 metastatic melanoma encorafenib Braftovi™ Array BioPharma BRAF V600E or V600K Oral July 2018 mutation 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 Lutathera™ Advanced Accelerator Gastroenteropancreatic Intravenous February 2018 dotatate Applications neuroendocrine tumors (GEP-NETs) Specialty Pipeline Update: March 2019 Page 7

New indications for approved oncology drugs

Generic name Brand name Manufacturer New Indication Date approved atezolizumab Tecentriq® Genentech With Abraxane (nab-paclitaxel) March 2019 chemotherapy for first-line treatment of unresectable locally advanced or metastatic triple-negative breast cancer (TNBC) that expresses PD-L1 trifluridine/tipiracil Lonsurf® Taiho Metastatic gastric or gastroesophageal March 2019 junction adenocarcinoma previously treated with at least 2 prior lines of chemotherapy that included a fluoropyrimidine, a platinum, either a taxane or irinotecan, and if appropriate, HER2/neu-targeted therapy pembrolizumab Keytruda® Merck Adjuvant treatment of melanoma March 2019

ibrutinib Imbruvica® Janssen/AbbVie Previously untreated adult CLL/SLL January 2019

cabozantinib Cabometyx® Exelixis Previously treated HCC January 2019

dasatinib Sprycel® BMS First-line in pediatric patients with newly January 2019 diagnosed Philadelphia chromosome- positive ALL (Ph+ ALL) olaparib Lynparza® AstraZeneca/ Maintenance therapy for deleterious or December 2019 Merck suspected deleterious germline or somatic BRCA-mutated advanced epithelial ovarian, fallopian tube or primary peritoneal cancer atezolizumab Tecentriq® Roche With Avastin®, paclitaxel and carboplatin December 2018 for first-line treatment of NSCLC pembrolizumab Keytruda® Merck Advanced hepatocellular carcinoma (HCC) November 2018

venetoclax Venclexta® Abbvie With azacitidine or decitabine or low- November 2018 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 With chemotherapy for certain adults with November 2018 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 Coagulation Factor X, Human Coagadex Bio Products Hereditary factor X deficiency younger September 2018 Laboratory than 12 nivolumab Opdivo® BMS Metastatic small cell lung cancer (SCLC) August 2018

lenvatinib Lenvima® Eisai HCC August 2018

ribociclib Kisqali® Novartis With fulvestrant for the treatment of July 2018 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

continued Specialty Pipeline Update: March 2019 Page 8

New indications for approved oncology drugs (continued)

Generic name Brand name Manufacturer New Indication Date approved 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: With June 2018 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 at May 2018 least 2 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 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 1 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, February 2018 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 Specialty Pipeline Update: March 2019 Page 9

New indications for approved oncology drugs (continued)

Generic name Brand name Manufacturer New Indication Date approved 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 With Herceptin® and chemotherapy for January 2018 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

Biosimilar product approvals in the past twelve months Reference Route of Month Generic name Brand name product Manufacturer Indication(s) administration approved trastuzumab-qyyp Trazimera™ Herceptin® Pfizer HER2-positive breast IV March 2019 cancer or gastric or gastroesophageal junction cancer trastuzumab-dttb Ontruzant® Herceptin® Samsung Bioepis/Merck HER2-positive breast IV December 2018 cancer or gastric or gastroesophageal junction cancer trastuzumab-pkrb Herzuma® Herceptin® Celltrion and Teva HER2-positive breast IV December 2018 cancer rituximab-abbs Truxima™ Rituxan® Celltrion and Teva NHL IV November 2018

pegfilgrastim-cbqv Udenyca™ Neulasta® Coherus BioSciences Neutropenia SC November 2018

adalimumab-adaz Hyrimoz™ Humira® Sandoz/Novartis Autoimmune SC October 2018

filgrastim-aafi Nivestym™ Neupogen® Pfizer Neutropenia IV/SC July 2018

pegfilgrastim-jmdb Fulphila™ Neulasta® Mylan/Biocon Neutropenia SC June 2018

epotin alfa-epbx Retacrit® Procrit®/Epogen® Pfizer/Hospira Anemia IV/SC May 2018 Specialty Pipeline Update: March 2019 Page 10

Specialty pipeline Route of Anticipated Generic name Brand name Manufacturer Indication(s) administration approval date* siponimod Mayzent™ Novartis Secondary progressive multiple Oral March 2019 sclerosis (SPMS) romosozumab Evenity™ Amgen/UCB Osteoporosis SC March 2019

cladribine Mavenclad™ EMD Serono/Ivax Short-course treatment of relapsing Oral March 2019 multiple sclerosis risankizumab Skyrizi™ AbbVie Plaque psoriasis SC April 2019

immune globulin N/A ADMA Biologics Primary immune deficiency disease IV 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 r/r FLT3-ITD AML Oral May 2019

onasemnogene Zolgensma® Novartis Spinal muscular atrophy Type 1 IV May 2019 abeparvovec (SMA1) celiprolol Edsivo™ Acer Vascular Ehlers-Danlos syndrome Oral June 2019

mannitol Bronchitol™ Chiesi Group and Cystic fibrosis Inhalation June 2019 Pharmaxis riluzole Nurtec™ Biohaven ALS Oral July 2019

afamelanotide Scenesse® Clinuvel Erythropoietic protoporphyria SC July 2019 Pharmaceuticals tafamidis meglumine Vyndaqel™ Pfizer Transthyretin amyloid Oral July 2019 cardiomyopathy (ATTR-CM) entrectinib N/A Genentech NTRK fusion-positive metastatic Oral August 2019 solid tumors or ROS1-positive NSCLC golodirsen N/A Sarepta DMD amendable to skipping IV August 2019 Exon 53 upadacitinib N/A Abbvie Rheumatoid arthritis Oral August 2019

polatuzumab vedotin N/A Genentech R/R diffuse large B-cell lymphoma IV August 2019

pexidartinib N/A Daiichi Sankyo Tenosynovial giant cell tumor Oral August 2019

fedratinib N/A Celegene Myelofibrosis Oral September 2019

PF708 (teriparatide) N/A Pfenex/Alvogen Osteoporosis SC October 2019

diroximel fumarate Vumerity™ Alkermes/Biogen Relapsing forms of MS Oral 4Q2019

tafamidis free acid N/A Pfizer ATTR-CM Oral November 2019

AR101 N/A Aimmune Peanut allergy Oral January 2020

* Anticipated approval dates are predictions made by Prime Therapeutics based on industry information. Specialty Pipeline Update: March 2019 Page 11

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

Autoimmune SB5 (adalimumab) N/A Samsung Autoimmune SC July 2019 (Humira® Bioepis biosimilar) PF-06410293 N/A Pfizer Autoimmune SC 4Q2019 (adalimumab) (Humira® biosimilar)

IV Oncology PF-05280014 N/A Pfizer HER2-positive IV March 2019 (trastuzumab) (Herceptin breast cancer biosimilar) ABP 980 Kanjinti™ Amgen/Allergan HER2-positive IV June 2019 (trastuzumab) (Herceptin breast cancer biosimilar) PF-0643935 N/A Pfizer NSCLC IV June 2019 (bevacizumab) (Avastin® biosimilar) PF-05280586 N/A Pfizer NHL IV July 2019 (Rituxan® biosimilar) *Anticipated approval dates are predictions m ade by Prime Therapeutics based on industry information.

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 benefit benefit Zolgensma® SMA1 May 2019 Spinraza® None $$ to (onasemnogene abeparvovec or AVXS-101) $$$ Novartis Lentiglobin™/Bluebird Bio Transfusion-dependent TBD Allogenic HSCT None $$ β-thalassemia/IV *Notations: $ < $0.08 per member per month (PMPM), $$ = $0.08- $0.39 PMPM, $$$ = $0.40- $2.00 PMPM, $$$$ > $2.01 PMPM

References 1. https://www.fiercepharma.com/pharma/j-j-s-depression-nasal-spray-spravato-carrying-big-expectations-and-restrictions-scores-fda. 2. https://www.fiercepharma.com/marketing/does-pfizer-s-xeljanz-share-its-safety-issues-burgeoning-jak-class. 3. https://www.globenewswire.com/news-release/2019/02/25/1741439/0/en/Alkermes-and-Biogen-Announce-U-S-Food-and-Drug-Administration-Acceptance-of-Diroximel-Fumarate-New-Drug-Application-for- Multiple-Sclerosis.html. 4. https://pharmaphorum.com/news/lilly-claims-fast-fda-review-for-emgality-in-cluster-headache/.

5. https://www.empr.com/home/news/dupixent-sbla-gets-priority-review-for-chronic-rhinosinusitis-with-nasal-polyps-indication/.

2992-B1 © Prime Therapeutics LLC 03/19