Pipeline Report August 2019

AcariaHealth Pipeline Report

August 2019 Pipeline Report Recent Drug Approvals August 2019

The AcariaHealth Pipeline Report is a quarterly publication, provided by Envolve Pharmacy Solutions, created to help clients prepare for shifts in pharmacy benefit management. The report includes updates across multiple disease states including recent and anticipated drug approvals, key changes in the biosimilar agent landscape, and notes on recent and anticipated generic product launches. This report should only be used as a guide, as information may have changed from the time of publication.

Recent Drug Approvals

FDA AcariaHealth Cost Drug Name Manufacturer Indication(s) Drug Class Approval (AH) Access Comments (AWP Package Price) Date Status

• One-time infusion. Zolgensma • Dramatic improvements in motor ability have been observed in infants who onasemnogene • Spinal muscular Neuromuscular $2.55 million / • Novartis 5/24/19 Limited Access received therapy. abeparvovec-xioi atrophy Type 1 agent one-time treatment • Approved with a Black Box Warning (BBW) re: acute serious liver injury. intravenous infusion • Spinraza is the only other FDA-approved agent.

Piqray • For relapsed or refractory HR+, HER2-negative, PIK3CA-mutant advanced or alpelisib • Novartis • Breast cancer Oncology 5/24/19 AH has access $18,600 metastatic disease in both men and postmenopausal women. oral tablets

Polivy • For use in combination with bendamustine and rituximab (BR). polatuzumab • Diffuse large B-cell $18,000 / cycle x 6 • Genentech Oncology 6/10/19 AH has access • Demonstrated significantly improved overall survival outcomes relative to vedotin-piiq lymphoma cycles total BR alone. intravenous infusion

Xpovio • For use in combination with dexamethasone for patients who have received at • Karyopharm selinexor • Multiple myeloma Oncology 7/3/19 Limited access least four prior therapies. $26,400 Therapeutics oral tablets • No other FDA-approved therapies exist for this indication.

Nubeqa darolutamide • Bayer • Prostate cancer Oncology 7/30/19 AH has access • Same mechanism of action and FDA-approved indication as Xtandi. $13,860 oral tablets

Turalio • For the treatment of adults who are not candidates for surgical treatment. • Tenosynovial giant pexidartinib • Daiichi Sankyo Oncology 8/2/19 Limited access • Approved with a BBW re: hepatotoxicity. Pending launch cell tumor (TGCT) oral capsules • No other FDA-approved systemic therapies exist for this indication.

Upcoming Products

Anticipated Drug Name Manufacturer Indication(s) Drug Class Mechanism of Action Comments Approval Date RXDX101 • Proposed for the treatment of ROS1-positive NSCLC, for which Xalkori is also • Non-small cell lung cancer Tyrosine kinase entrectinib • Genentech Oncology FDA-approved. 8/18/19 • NTRK-positive solid tumors inhibitor oral capsules • Vitrakvi is FDA-approved for NTRK-positive solid tumors. SRP-4053 • Proposed for the treatment of DMD with mutations amenable to exon • Sarepta • Duchenne Muscular Musculoskeletal Antisense golodirsen 53 skipping. 8/19/19 Therapeutics Dystrophy (DMD) disorders oligonucleotide intravenous infusion • No exon 53-specific therapies currently exist. ABT-494 • High selectivey for JAK1. upadacitinib • AbbVie • Rheumatoid arthritis Immunology JAK inhibitor • Once daily therapy. 8/20/19 oral tablets • Would compete with Xeljanz, Olumiant, injectable biologic DMARDs. SAR302503 • Approximately 70% of patients with myelofibrosis have insufficient response or fedratinib • Celgene • Myelofibrosis Oncology JAK-2 / FLT-3 inhibitor 9/3/19 do not tolerate Jakafi which is another therapy for myelofibrosis. oral capsules Scenesse • Erythropoietic Melanocyte stimulating afamelanotide • Clinuvel Dermatology • Administered bimonthly as a bioabsorbable implant. 10/6/19 Protoporphyria (EPP) hormone agonist subcutaneous implant Vumerity NF-E2 and NF-kappa • Proposed for relapsing remitting MS. • Alkermes diroximel fumarate • Muliple Sclerosis (MS) Neurology transcription factor • Represents another oral fumarate option. 10/17/19 • Biogen oral capsules stimulator • Presumably less gastrointestinal side effects relative to Tecfidera. RTH258 • Wet, age-related brolucizumab • Novartis Ophthalmology VEGF inhibitor • Potential competitor to Eylea. 11/21/19 macular degeneration intraocular injection ACE536 • Celgene / Type II activin receptor luspatercept • Beta-thalassemia anemia Hematology • Current standard of care is lifelong red blood transfusions. 12/4/19 Acceleron fusion protein subcutaneous injection RVT-802 • One-time treatment per lifetime. • Complete DiGeorge Thymic tissue allogeneic thymic tissue • Enzyvant Endocrinology • Demonstrated an overall survival of 72% among 85 patients with 12/5/19 syndrome regenerative therapy tissue replacement congenital athymia. SEG101 Anti-P-selectin • Reduced the median annual rate of vaso-occlusive crises leading to healthcare crizanlizumab • Novartis • Sickle cell disease Hematology 1/16/20 monoclonal antibody visits by 45.3% vs placebo in a Phase 2 trial. intravenous infusion E7438 • For metastatic or locally advanced disease that is not amenable to tazemetostat • Epizyme • Epithelioid sarcoma Oncology EZH2 enzyme inhibitor curative surgery. 1/23/20 oral tablets • There are currently no other FDA-approved therapies. ALD403 • Alder • Proposed for episodic and chronic migraines. eptinezumab • Migraine headaches Neurology CGRP antagonist 2/22/20 BioPharmaceuticals • 30-minute infusion once every 12 weeks in a hospital setting. intravenous infusion

Upcoming Products

Anticipated Drug Name Manufacturer Indication(s) Drug Class Mechanism of Action Comments Approval Date VX445 + Symdeko Cystic fibrosis • For patients 12 years of age and older who are homozygous for the CFTR-F508del elexacaftor + tezacaftor / transmembrane • Vertex • Cystic fibrosis Respiratory mutation or with 1 copy of the CFTR-F508del mutation and a minimal function 3/20/20 ivacaftor conductance regulator CFTR mutation (heterozygous). oral tablets modulator RPC1063 Sphingosine • Relapsing forms of ozanimod • Celgene Neurology 1-phosphate 1 and 5 • Same mechanism of action as Gilenya, but potentially less cardiac adverse effects. 3/25/20 multiple sclerosis oral capsules receptor modulator SAR650984 • Proposed for use in combination with pomalidomide and dexamethasone for Anti-CD38 monoclonal isatuximab • Sanofi • Muliple myeloma Oncology third-line treatment. 4/30/20 antibody intravenous infusion • Same mechanism of action and indication as Darzalex. BMN 270 valoctocogene Coagulation • For the treatment of adults with severe disease. • BioMarin • Hemophilia A Gene therapy 2020 roxaparvovec Disorders • Current standard of care is factor VIII replacement therapy or Hemlibra. intravenous infusion • IV infusion twice weekly for 4 consecutive weeks. Prochymal Immunology / • Acute graft vs. • Among 50 patients who received ≥ 1 treatment infusion, the Day 100 mortality remestemcel-L • Mesoblast Autoimmune Stem cell therapy 2020 host disease rate was 22%, in contrast to Day 100 mortality rates as high as 70% in intravenous infusion Disease historical controls.

Biosimilars

Status / Estimated Biosimilar Currently Drug Name Manufacturer Biosimilar Reference Drug Indication(s) Drug Class Comments Approval Launched? Kanjinti • Breast cancer Approved 6/13/19; • Another biosimilar to Herceptin, after trastuzumab-anns • Amgen / Allergan Herceptin Oncology Yes - Kanjinti • Gastric cancer Launched Herzuma, Ogivri, Ontruzant, Trazimera. intravenous infusion • Colorectal cancer Zirabev • Lung cancer Approved 6/27/19; bevacizumab-bvzr • Pfizer Avastin • Brain cancer Oncology Yes - Mvasi • Another biosimilar to Avastin, after Mvasi. Pending launch intravenous infusion • Renal cell carcinoma • Cervical cancer

Ruxience • Non-Hodgkin's Approved 7/23/19; rituximab-pvvr • Pfizer Rituxan Oncology No • Another biosmilar to Rituxan, after Truxima. lymphoma Pending launch intravenous infusion

Hadlima • Rheumatoid arthritis • Another biosimilar to Humira. Approved 7/23/19; adalimumab-bwwd • Samsung Bioepis Humira • Psoriasis Immunology No • The manufacturer has reached a patent Pending launch subcutaneous injection • Crohn's disease settlement that allows for launch of 6/30/23. TX-01 BLA is under • Tanvex • Chemotherapy- Yes - Zarxio and • Another biosimilar to Neupogen, after Zarxio filgrastim biosimilar Neupogen Hematology FDA review; Pharmaceuticals induced neutropenia Nivestym and Nivestym. subcutaneous injection PDUFA Date: 8/1/19 PF-06410293 • Rheumatoid arthritis BLA is under Rheumatology / • Another biosimilar to Humira, after Amjevita, adalimumab biosimilar • Pfizer Humira • Psoriasis FDA review; No Immunology Cyltezo and Hyrimoz. subcutaneous injection • Crohn's disease PDUFA Date: 10/1/19 LAEP2006 BLA is under • Chemotherapy- Yes - Fulphila, • Another biosimilar to Neulasta, after pegfilgrastim biosimilar • Sandoz Neulasta Hematology FDA review; induced neutropenia Udenyca Fulphila and Udenyca. subcutaneous injection PDUFA Date: 10/2/19 PF-708 BLA is under • Would be the first FDA-approved biosimilar teriparatide biosimilar • Alvogen / Pfenex Forteo • Osteoporosis Skeletal agent FDA review; No to Forteo. subcutaneous injection PDUFA Date: 10/7/19 ABP 710 • Rheumatoid arthritis BLA is under Rheumatology / Yes - Inflectra, • Another biosimilar to Remicade, after infliximab biosimilar • Amgen Remicade • Psoriasis FDA review; Immunology Renflexis Infectra and Renflexis. intravenous infusion • Crohn's disease PDUFA Date: 10/17/19

Generic Agents - Recent Approvals

Generic Name Brand Name Manufacturer Market Launch Date

• Mylan erlotinib Tarceva 25 mg, 100 mg, 150 mg 5/9/19 • Teva • Mylan fulvestrant Faslodex 5/30/19 • Teva sildenafil Revatio oral suspension • Novitium 5/31/19 • Fresenius icatibant Firazyr • InnoPharma 7/15/19 • Sandoz

Generic Agents - Pipeline Agents

Generic Name Brand Name Manufacturer Anticipated Launch Date

abiraterone acetate Zytiga 500 mg • Teva H2 2019

thalidomide Thalomid • Lannett Q3 2019

teriparatide Forteo • Teva Q3 2019 • Teva deferasirox Jadenu Q4 2019 • Zydus epoprostenol sodium Veletri • Sun Q4 2019 • Par everolimus Afinitor Q4 2019 • Endo emtricitabine / tenofovir disoproxil fumarate Truvada • Teva 9/30/20

efavirenz / emtricitabine / tenofovir disoproxil fumarate Atripla • Teva 9/30/20 • Par sapropterin dihydrochloride Kuvan tablets 10/1/20 • Endo