2ND4TH QUARTERQUARTER 2018 2019 PIPELINE REPORT

2ND QUARTER 2019 PIPELINE REPORT

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PIPELINE HIGHLIGHTS:

Recent Approvals

• Esperoct® (turoctocog alfa pegol) – Hemophilia A • Cablivi® (caplacizumab-yhdp) – Acquired thrombotic thrombocytopenic purpura (aTTP) • Asparlas® (calaspargase PEGOL-MKNL) – Acute lymphoblastic leukemia (ALL) • Gamifant® (-LZSG) – Hemophagocytic lymphohistiocytosis (HLH) • Elzonris® (tagraxofusp-ERZS) – Blastic plasmacytoid dendritic cell neoplasm (BPDCN) Anticipated FDA Approvals

• Zynquista (sotagliflozin)– Type 1 diabetes patients who lack adequate blood sugar control on therapy 3/2019 • Mayzent (siponimod) – Secondary progressive multiple sclerosis (SPMS) 3/2019) • Mavenclad (cladribine) – Relapsing-remitting multiple sclerosis 3/2019 • Risenkizumab – Plaque psoriasis 4/2019

Market Launched Biosimilar Approvals

• Udenyca (-cbqv)– 33% Savings over reference product Neulasta (pegfilgrastim)

Anticipated Biosimilars FDA Launch Dates

• Ogivri (-dkst) – Biosimilar for reference product Herceptin – FDA Approved 12/2017; Anticipated Launch Date June 2019 • Mvasi (-awwb) – Biosimilar for reference product Avastin – FDA Approved 9/2017; Anticipated Launch Date July 2019 • Ontruzant (trastuzumab-dttb) – Biosimilar for reference product Herceptin – FDA Approved 1/2019; Anticipated Launch Date 2019-2020 • Hyrimoz (adalimumab-adaz) – Biosimilar for reference product Humira – FDA Approved 10/2018; Anticipated Launch Date 2022-2023 • Truxima (-abbs) – Biosimilar for reference product Rituxan – FDA Approved 11/2018; Anticipated Launch Date Q1-2 2019

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Recent FDA Approvals

Disease or Therapy Options Approval Estimated Drug Name / Treatment Administration Clinical Comments Approximate Date WAC / Year Manufacturer Indication Comments WAC/Year

Approved $270,000 Cablivi Bleeding disorder: Rare disease, causes First-in-class product Therapy Options: per episode (caplacizumab- Acquired thrombotic episodes of life- provides a significant 02/6/2019 ››Standard (mfg- yhdp) thrombocytopenic threatening bleeding. improvement over treatment has estimated purpura (aTTP) Frequency and duration previous standard Sanofi been plasma average) of episodes vary. treatment. exchange and Anticipated First dose (IV) and immunosuppressant Coverage: several daily subQ drugs. Cablivi is Pharmacy doses given in hospital; given in addition to (for subQ continued subQ as these. doses) outpatient.

Approved $678,038 Gamifant Inflammatory Given IV. Usually started Gamma - Therapy Options 11/20/2018 based on 9 (emapalumab- blood disease: in hospital, may move blocking monoclonal (second-line): kg patient LZSG) Hemophagocytic to infusion center after antibody ››Stem Cell dosed at 1 lymphohistiocytosis stabilized. Duration of Novimmune, Sobi Second-line therapy transplant-- mg/kg twice (HLH) therapy variable. (first-line therapy: $350,000 to weekly Ultra-rare, rapidly immunosuppressants $800,000. Anticipated progressive, highly fatal + steroids) Coverage: disease; most often Medical affects infants from birth-18 mos.

Approved $205,212 Elzonris Rare Blood Cancer: IV infusion Diphtheria toxin Therapy Options: Based on (tagraxofusp- Blastic plasmacytoid (every 4 weeks) conjugated to human 12/21/2018 None, BPDCN 70kg person, ERZS) dendritic cell neoplasm -3 (IL-3) currently has no 2-5 day (BPDCN) protein, causing cell Stemline approved standard cycles death Being evaluated for therapies available Anticipated other types of leukemia. Black box warning Coverage: about potentially fatal Medical side effect.

Approved TBD Asparlas Blood & Bone Given IV as part of a ALL – 75% of American Therapy Options: (Calaspargase Marrow Cancer: multi-drug regimen childhood leukemia 12/20/2018 Likely to be a ››Oncaspar PEGOL-MKNL) Acute lymphoblastic every 21 days. and 78% in Europe differentiating (pegaspargase) leukemia (ALL) factor Servier ››Less frequent dosing Market launch $86,396 (1.73m2 Pharmaceuticals, than Oncaspar expected Q1 2019 adult at 3 doses for Anticipated induction and 3 for Shire ›Oncaspar preferred for Coverage: › consolidation) Medical patients with IV access problems.

Approved TBD Esperoct Hemophilia A IV infusion (twice PEGylated Coagulation Factor (turoctocog alfa weekly or every 4 days recombinant human VIII Therapy 02/19/2019 Anticipated pegol) to prevent bleeding Factor VIII; long Options: Coverage: episodes) acting formulation Medical Novo Nordisk ››Advate – $492,960 of NovoEight ›NovoEight – (Turoctocog Alfa) › $662,688 Market launch ››Xyntha – $492,960 expected 2020 ››Nuwiq – $562,094 ››Recombinate – $369,720

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Recent FDA Approvals (continued)

Disease or Therapy Options Approval Estimated Drug Name / Treatment Administration Clinical Comments Approximate Date WAC / Year Manufacturer Indication Comments WAC/Year

Approved TBD Herzuma Breast cancer: Anti-HER2 antibody Herceptin is a first-line Therapy Options: (Trastuzumab- HER2-positive breast administered IV chemo agent for HER- 12/14/2018 Expected ››Herceptin Pkrb) cancer 2+ breast cancer. to provide Biosimilar to reference (trastuzumab) - significant Celltrion drug Herceptin Not interchangeable $81,073 (76.5kg @ savings over with Herceptin, must 6mg/kg per cycle Established safety, Herceptin obtain new rx for for 1 year) efficacy data is based on when Herzuma This is one of studies of Herceptin launched several Herceptin Market launch biosimilars. Anticipated expected Q3 2019 Coverage: Pharmacy Approved TBD Ontruzant Cancer: Anti-HER2 antibody Herceptin is a first-line Therapy Options: 01/18/2019 (Trastuzumab- HER2-positive breast administered IV chemo agent for HER- Expected ››Herceptin DTTB) cancer, Gastric cancer, 2+ breast cancer. to provide Biosimilar to reference (trastuzumab) - Gastroesophageal significant Merck & Co drug Herceptin Not interchangeable $81,073 (76.5kg @ junction cancer savings over with Herceptin, must 6mg/kg per cycle Established safety, Herceptin obtain new rx for for 1 year) efficacy data is based on Ontruzant This is one of Anticipated studies of Herceptin several Herceptin Coverage: Market launch biosimilars. Pharmacy expected 2019-2020 Approved TBD Hyrimoz Inflammatory: Tumor necrosis factor Not interchangeable Therapy Options: 10/31/2018 (Adalimumab- Treatment of rheumatoid (TNF)-blocker injectable with Humira, must Expected ››Humira ADAZ) arthritis, plaque Biosimilar for reference obtain new rx for to provide (adalimumab)-- psoriasis, Crohn’s drug Humira Hyrimoz significant Sandoz $67,263 disease, and ulcerative savings over Established safety, Market launch colitis UK approved Humira when efficacy data is based on expected 2022-2023 adalimumab launched studies of Humira biosimilar saved Anticipated $386 million USD Coverage: or 75% total UK Pharmacy Humira spend

Anticipated FDA Approvals

Expected Drug Name / Disease or Administration FDA Review Indication Clinical Comments Therapy Options Manufacturer Comments Date

03/1/2019 Mayzent Multiple Sclerosis: Oral, once daily Sphingosine 1-phosphate Therapy Options: (siponimod) Secondary (S1P) receptor modulator SPMS leads to progressive, If still experiencing progressive multiple Novartis irreversible disability Mayzent is one of only relapses : sclerosis (SPMS) two drugs shown to slow ››Gilenya (Novartis) progression of SPMS. The other, mitoxantrone, has ››Ocrevus (Roche) serious side effects such as ››Lemtrada (Sanofi) heart failure and cancer. ››Tysabri (Biogen) SPMS without relapses: ››Mitoxantrone (generic) 03/20/2019 Solriamfetol Sleep Disorders: Estimated 65% excessive Solriamfetol will offer Therapy Options: Excessive daytime sleepiness persists in CPAP alternative for intolerant Jazz SK ››Positive Airway Pressure sleepiness in patients CPAP patients Biopharma- therapy or Continuous obstructive sleep ceuticals New Chemical Entity, Orphan Positive Airway Pressure apnea or narcolepsy Drug (CPAP)

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Anticipated FDA Approvals (continued)

Expected Drug Name / Disease or Administration FDA Review Indication Clinical Comments Therapy Options Manufacturer Comments Date

03/22/2019 Zynquista Diabetes: Oral Diabetic ketoacidosis, Therapy Options: (sotagliflozin) For patients with a serious diabetes Used along with insulin None type 1 diabetes who complication, was more Lexicon lack adequate blood frequent in those given Phamaceuticals; sugar control on sotagliflozin compared to Sanofi insulin therapy. insulin alone. In Jan 2019, the FDA Advisory Committee were evenly divided on whether the benefits of Zynquista outweighed the risks.

03/30/2019 Mavenclad Multiple Sclerosis: Oral Nucleoside analog Therapy Options: (cladribine) Relapsing-remitting that depletes B and T Unique Dosing Regimen: ››Gilenya (Novartis) multiple sclerosis lymphocytes EMD Serono 2 courses of 5 tablets one ››Ocrevus (Roche) Approved in UK month apart for 2 years, based on body weight ››Lemtrada (Sanofi) ››Tysabri (Biogen)

04/6/2019 Selinexor Bone Marrow Oral (twice weekly) option First in class, oral Selective Therapy Options: Cancer: for patients battling highly Inhibitor of Nuclear Export Karyopharm ››Bortezomib (Velcade) Penta- Refractory resistant, refractory myeloma compound Multiple Myeloma ››Carflizomib (Kyprolis) ››Ixazomib (Ninlaro)

04/25/2019 risankizumab Plaque Psoriasis SubQ injection every 12 weeks Interleukin-23 inhibitor Therapy Options: Moderate to Severe after induction AbbVie/BI 2017 study results show ››Humira (adalimumab) Being reviewed for promising results compared ››Enbrel () Crohn’s & Ulcerative to Stelara and Humira Colitis ››Stelara (ustekinumab) As more competitor products become available, price ››Cosentyx (secukinumab) competition and formulary ››Taltz (lxekizumab) exclusivity present challenges ›Siliq (brodalumab) to Humira and Enbrel. › ››Tremfya (guselkumab)

05/13/2019 Evenity Osteoporosis: SubQ injection once monthly First in class mechanism of Therapy Options: (romosozumab) Osteoporosis in for 1 yr action (sclerosin inhibitor) (based ››Actonel (risedronate) postmenopausal on BLA Amgen/UCB Compared to alendronate women with high risk ››Boniva (ibandronate) resubmission alone, Phase III trials showed of fractures date of July reduced vertebral fracture ››Tymlos (abaloparatide) 13, 2018) risk and increased bone ››Forteo (teriparatide) mineral density Reports of cardiovascular safety concerns in 2.5% trial patients

05/25/2019 Quizartinib Leukemia: Oral FLT-3 inhibitor Therapy Options: Relapsed/ refractory Ambit Patients with AML with FLT3- Quizartinib has been granted Salvage chemotherapy: FLT3-ITD acute Biosciences ITD gene mutations have a Breakthrough Therapy myeloid leukemia ›› Corporation; worse overall prognosis than designation and Priority Daiichi Sankyo those without this mutation. Review status. This means ››Azacitidine or decitabine the FDA must review it for + approval more quickly than it does drugs without this status.

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Biosimilar Pipeline

Biosimilar Reference Approval Launch Reference Biosimilar Name WAC / Product WAC / Interchangeable Disease Category Date Date Product Year Cost Year Cost

May 2018 June 2018 RetacritTM ** Retacrit - Epogen Biosimilar No Hematopoietic: Treatment of (-epbx) $154 Procrit Retacrit -$154 anemia due to chronic kidney (Epoetin Alfa) disease, Zidovudine in HIV- Epogen - $232 infected patients, chemotherapy Procrit - $360 in cancer patients, and reduction of allogeneic red blood cell transfusion in patients’ elective surgery December To Be Herzuma TBD Upon Interchangeability 2018 Determined (trastuzumab-pkrb) Launch is not anticipated

Expected June 2019 PF0528014 [Pfizer] TBD Upon Interchangeability Cancer: Treatment of Human FDA Review (trastuzumab) Launch is not anticipated Epidermal Herceptin Receptor 2 (HER2) adjuvant Q1 2019 $32,000 (trastuzumab) breast cancer, metastatic January To Be Ontruzant TBD Upon Interchangeability breast cancer, and metastatic 2019 Determined (trastuzumab-dtb) Launch is not anticipated gastric cancer

December June 2019 Ogivri TBD Upon No 2017 (trastuzumab-dkst) Launch

Expected To Be Grastofil TBD Upon Interchangeability Hematopoietic: To reduce FDA Review Determined () Launch is not anticipated the incidence of infection TBD 2018 in patents receiving chemotherapy, reduce the March 2015 September Zarxio® ** $4,390 No duration and time to recovery 2015 Neupogen from neutropenia caused by (filgrastim-sndz) $5,314 (filgrastim) chemotherapy, mobilization August 2012 2015 Granix® ** $3,999 No of progenitor blood cells for (tbo-filgrastim) collection by leukapheresis, and reducing the incidence July 2018 October NivestymTM ** $3,504 No and duration of complications 2018 (filgrastim-aafi) due to severe neutropenia.

September July 2019 Mvasi TBD Upon Avastin $162,576 No Cancer: Treatment of 2017 (bevacizumab- Launch (bevacizumab) Metastatic colorectal awwb) cancer, Non-squamous non-small cell lung cancer, Glioblastoma, Metastatic renal cell carcinoma, Persistent, recurrent, or metastatic carcinoma of the cervix December No US IxifiTM Not antici- No Immunological Agent: 2017 Launch (infliximab-qbtx) pated to be Ankylosing spondylitis, launched Crohn’s disease (fistulizing), due to adult, Crohn’s disease, adult acquisition Remicade and pediatric (6 years or $49,340 (infliximab) older), Plaque psoriasis, April 2017 July 2017 Renflexis® $31,831 No ** Psoriatic arthritis, Rheumatoid (infliximab-abda) arthritis in combination with methotrexate, Ulcerative April 2016 November Inflectra® $39,980 No ** colitis, adult 2016 (infliximab-dyyb) August 2017 2023 CyltezoTM TBD Upon No (adalimumab-adbm) Launch Immunosuppressant: Treatment of rheumatoid September 2023 AmjevitaTM TBD Upon Humira No $63,336 arthritis, plaque psoriasis, 2016 (adalimumab-atto) Launch (adalimumab) Crohn’s disease, and ulcerative October To Be Hyrimoz TBD Upon No colitis 2018 Determined (adalimumab) Launch

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Biosimilar Pipeline (continued)

Biosimilar Reference Approval Launch Reference Biosimilar Name WAC / Product WAC / Interchangeable Disease Category Date Date Product Year Cost Year Cost

August 2016 2019-2029 Erelzi® TBD Upon Enbrel $64,629 No Immunosuppressant: (etanercept-szzs) Launch (etanercept) Ankylosing spondylitis, Juvenile idiopathic arthritis (2 years or older), Plaque psoriasis adult, Psoriatic arthritis, Rheumatoid arthritis

November Q 1-2 2019 TruximaTM TBD Upon Rituxan $40,712 Interchangeability Cancer: Treatment of patients 2018 (rituximab-abbs) Launch (rituximab) is not anticipated with non-Hodgkin’s lymphoma, (BR&R, 2019) chronic lymphocytic leukemia, rheumatoid arthritis, granulomatosis with polyangiitis and microscopic polyangiitis.

June 2018 July 2018 FulphilaTM ** $4,175 No Hematopoietic: Reduce (pegfilgrastim- incidence of infection, jmdb) as manifested by febrile neutropenia, in patients with November January Udenyca** $4,175 No non‑myeloid malignancies 2018 2019 receiving myelosuppressive (pegfilgrastim- Neulasta cbqv) $6,231 anti‑cancer drugs associated (pegfilgrastim) with a clinically significant Expected To Be LapelgaTM TBD Upon Interchangeability incidence of febrile FDA Review Determined TPI‑120 Launch is not anticipated neutropenia. 2018 CHS-1701 Note: Biosimilar approval (pegfilgrastim) does not extend to Radiation Induced Neutropenia.

** Green boxes above indicate launched products.

The above information was assembled from government and clinical resources for knowledge purposes only. Information and drugs were selected by clinicians based on therapy and potential clinical impact without any manufacture affiliations or conflicts of interest. Approval status, dates, and WAC price are subject to variation. This document should not be exclusively used for decision-making purposes. WAC pricing data should be used for benchmarking purposes only. Prices listed above should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer.

Bibliography

IPD Analytics, LLC. (2018, December 15). IPD Analytics. Retrieved from http://www.ipdanalytics.com/ BR&R. (2019, January 18). Biosimilar Approval Status. Retrieved from BR&R Biosimilars Review & Report: https://biosimilarsrr.com/us-biosimilar-filings/ CenterWatch. (2019, February 15). 2019 FDA Approved Drugs. Retrieved from Centerwatch: https://www.centerwatch.com/drug-information/fda-approved-drugs/ Generics and Biosimilar Initatives. (2018, May). Biosimilars approved in the US. Retrieved from gabionline.net: www.gabionline.net/Biosimilars/General/Biosimilars-approved-in-the-US https://www.centerwatch.com/drug-information/fda-approved-drugs/. (n.d.). 2019 FDA Approved Drugs. Retrieved from CenterWatch. MarketWatch, Inc. (2018, August 30). Bayer Receives FDA Approval for Jivi®, New Hemophilia A Treatment With Step-Wise Prophylaxis Dosing Regimen . Retrieved from marketwatch.com: https://www.marketwatch.com/press-release/bayer-receives-fda-approval-for-jivi-new-hemophilia-a-treatment-with-step-wise-prophylaxis-dosing-regimen-2018-08-30 National Comprehensive Cancer Network. (2019, February 8). Breast Cancer, Version 4.2018 . Retrieved from NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines): https://www.nccn.org/professionals/physician_gls/pdf/breast.pdf U.S. Food and Drug Administration. (2017, September 07). FDA.gov. Retrieved from New Drugs at FDA: CDER’s New Molecular Entities and New Therapeutic Biological Products: https://www.fda.gov/Drugs/DevelopmentApprovalProcess/DrugInnovation/default.htm U.S. Food and Drug Administration. (2018, May 18). FDA approves Retacrit as a biosimilar to Epogen/Procrit. Retrieved from FDA.gov: https://www.fda.gov/drugs/informationondrugs/approved- drugs/ucm607723.htm U.S. Food and Drug Administration. (2018, May). FDA-Approved Biosimilar Products. Retrieved from FDA.gov: https://www.fda.gov/Drugs/DevelopmentApprovalProcess/HowDrugsareDevel- opedandApproved/ApprovalApplications/TherapeuticBiologicApplications/Biosimilars/ucm580432.htm U.S. Food and Drug Administration. (2018, Feb). NDA and BLA Calendar Year Approvals. Retrieved from FDA.gov: https://www.fda.gov/Drugs/DevelopmentApprovalProcess/ HowDrugsareDevelopedandApproved/DrugandBiologicApprovalReports/NDAandBLAApprovalReports/ucm373413.htm U.S. Food and Drug Administration. (2018). Press Announcements - New Drug Approvals. Retrieved from FDA.gov: https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/default.htm

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