Pipeline Report Recent Specialty Drug Approvals February 2020

The Envolve Pharmacy Solutions Pipeline Report is a quarterly publication, 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 Specialty Drug Approvals

FDA AcariaHealth Cost Drug Name Manufacturer Indication(s) Drug Class Approval (AH) Access Comments (AWP Package Price) Date Status Givlaari • Approved for prophylaxis of acute attacks. givosiran • Alnylam • Hepatic porphyria Gastrointestinal 11/20/19 Limited access $561,600 / year • Is the first agent to be FDA-approved for this indication. subcutaneous injection

Oxbryta • Once daily oral therapy. • Global Blood • Potentially disease-modifying. voxelotor • Sickle cell disease Hematology 11/25/19 Limited access $150,005 / year Therapeutics • Will be used as subsequent and/or concomitant therapy after oral tablets or with hydroxyurea.

Vyondys 53 • First agent to be FDA-approved for DMD with exon 53 • Duchenne muscular gene mutations. $748,800 / year golodirsen • Sarepta Musculoskeletal 12/12/19 Limited access dystrophy (DMD) • FDA approval was based largely on changes in muscle (25 kg child) intravenous infusion dystrophin levels. Padcev • For patients who have previously received a programmed death enfortumab receptor-1 (PD-1) or programmed death-ligand 1 (PD-L1) inhibitor, • Astellas • Urothelial cancer Oncology 12/18/19 Limited access $546,912 / year vedotin-ejfv and a platinum-containing chemotherapy in the neoadjuvant/ intravenous infusion adjuvant, locally advanced or metastatic setting. Enhertu • The linker-payload combination allows for a higher drug-to- fam-trastuzumab • Daiichi Sankyo • Breast cancer Oncology 12/20/19 Limited access antibody ratio of ~8, which may help target low expressing HER2 $187,351 / year deruxtecan-nxki • AstraZeneca tumors by supplying more payload per antibody to a tumor. intravenous infusion

Ayvakit • For the treatment of adult patients with unresectable or metastatic • Gastrointestinal stromal disease harboring a PDGFRA exon 18 mutation, including PDGFRA avapritinib • BluePrint Medicines Oncology 1/9/20 Limited access $460,800 / year tumors D842V mutations. oral tablets • Is the only agent to be FDA-approved for this subpopulation. Tepezza • Genmab • Is the first treatment shown to reduce proptosis during active $411,280 / one-time teprotumumab-trbw • Horizon • Graves' ophthalmopathy Endocrinology 1/21/20 Limited access disease, in addition to treating other painful symptoms. course of therapy intravenous infusion Pharmaceuticals Tazverik • For metastatic or locally advanced disease that is not amenable to tazemetostat • Epizyme • Epithelioid sarcoma Oncology 1/23/20 Limited access curative surgery. Pending launch oral tablets • There are currently no other FDA-approved therapies.

Recent Non-Specialty Drug Approvals

Cost Drug Name Manufacturer Indication(s) Drug Class FDA Approval Date Comments (AWP Package Price) Xcopri • For use as adjunctive therapy. cenobamate • SK Biopharmaceuticals • Partial onset seizures Neurology 11/21/19 Pending launch • Multiple other therapies for partial onset seizures exist. oral tablets Ervebo Ebola zaire • Ebola virus infection Infectious • Merck 12/19/19 • First FDA-approved vaccine against Ebola virus disease. Pending launch vaccine, live prophylaxis disease intramuscular injection Caplyta • Demonstrated a positive metabolic, cardiovascular, and motor lumateperone • Intra-Cellular Therapies • Schizophrenia Psychiatry 12/20/19 adverse event profile. $19,008 / year oral capsules • Multiple other atypical antipsychotics are currently available. Dayvigo • Eisai • Same mechanism of action as Belsomra. lemborexant • Insomnia Sleep disorders 12/20/19 Pending launch • Purdue Phamaceuticals • Similar clinical utility. oral tablets Ubrelvy • First oral CGRP antagonist to be FDA-approved. • Allergan ubrogepant • Acute migraine pain Neurology 12/23/19 • For acute migraine treatment only, not indicated for $12,240 / year • Merck oral tablets migraine prophylaxis. Palforzia peanut (Arachis • Initial dosing approved for use in children aged 4-17 years. hypogaea) allergen • Approved with a Black Box Warning re: risk of treatment-induced • Aimmune • Peanut allergy Immunology 1/31/20 Pending launch powder-dnfp anaphylaxis. oral capsules • No other FDA-approved therapies exist. and sachets

Upcoming Specialty Products

Anticipated Drug Name Manufacturer Indication(s) Drug Class Mechanism of Action Comments Approval Date 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 MEDI551 • Neuromyelitis optica • MedImmune Anti-CD19 monoclonal • Would compete with Soliris. inebilizumab and neuromyelitis optica Ophthalmology 2/27/20 • AstraZeneca antibody • Ultomiris is also being studied for the same indication. intravenous infusion spectrum disorders RPC1063 Sphingosine • Relapsing forms of • Same mechanism of action as Gilenya, but potentially less cardiac ozanimod • Celgene Neurology 1-phosphate 1 and 5 3/25/20 multiple sclerosis adverse effects. oral capsules receptor modulator MitoGel • Would be the only FDA-approved non-surgical treatment for this indication. • UroGen mitomycin • Urothelial carcinoma Oncology DNA synthesis inhibitor • Proposed for the treatment of low-grade upper tract disease that is unamenable 4/18/20 Pharmaceuticals bladder instillation gel to endoscopic resection or with contraindication to nephroureterectomy. 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. RG6168 • Neuromyelitis optica Anti-interleukin-6 • Demonstrated benefit in both AQP4-positive and negative subjects. satralizumab • Genentech and neuromyelitis optica Ophthalmology 4/30/20 receptor antibody • Administered as a monthly subcutaneous injection after an initial loading phase. subcutaneous injection spectrum disorders RG7916 • Proposed for the treatment of SMA Types 1, 2, and 3. • PTC Therapeutics • Spinal muscular atrophy risdiplam Musculoskeletal SMN2 gene splicer • Would be the first daily oral therapy approved for SMA. 5/24/20 • Roche (SMA) oral therapy • Potential competitor to Spinraza and Zolgensma. Instiladrin nadofaragene • Ferring • Non-muscle invasive • Proposed for BCG-refractory disease; treatment is applied once every 12 weeks. Oncology Gene therapy 5/25/20 firadenovec Pharmaceuticals bladder cancer • Keytruda is FDA-approved for the same indication. intravesical injection Selective inhibitor of INCB 54828 fibroblast growth factor • Proposed for the treatment of advanced/ metastatic or surgically unresectable pemigatinib • Incyte • Cholangiocarcinoma Oncology 5/30/20 receptor (FGFR)-1, -2 disease with FGFR-2 translocation in patients who failed previous therapy. oral therapy and -3 IMMU-132 • Antibody-drug conjugate (ADC). • Triple negative breast Trop-2 receptor sacituzumab govitecan • Immunomedics Oncology • Impressive clinical activity seen in a refractory setting. 6/2/20 cancer (TNBC) monoclonal antibody intravenous infusion • Would be the first and only ADC approved for the treatment of metastatic TNBC. Ocaliva • Non-alcoholic Farnesoid X-activated • New indication for Ocaliva. obeticholic acid • Intercept Hepatology 6/26/20 hepatosteatosis (NASH) receptor agonist • Would be the first FDA-approved pharmacologic therapy for NASH. oral tablets AZD6244 • Neurofibromatosis type • AstraZeneca • Proposed for the treatment of pediatric patients aged three years and older selumetinib 1 (NF1) with plexiform Endocrinology MEK 1/2 inhibitor Q2 2020 • Merck with symptomatic, inoperable PNs. oral capsules neurofibromas (PN)

Upcoming Specialty Products

Mechanism of Anticipated Drug Name Manufacturer Indication(s) Drug Class Comments Action Approval Date

MP0112 Vascular • Age-related macular endothelial • In two phase III trials, treatment with abicipar pegol given every 8 or 12 weeks was non- abicipar pegol • Allergan Ophthalmology 7/9/20 degeneration growth factor inferior to Lucentis given every 4 weeks. intraocular injection (VEGF) inhibitor Anti-B cell GSK2857916 maturation • Proposed as monotherapy in patients who have failed at least three prior lines of belantamab mafodotin • GlaxoSmithKline • Multiple myeloma Oncology antigen (BCMA) therapy, including an anti-CD38 antibody and are refractory to a proteasome inhibitor 7/21/20 intravenous infusion monoclonal and an immunomodulatory agent. antibody UX 007 • Long-chain fatty Fatty acid • Currently available therapies include avoidance of fasting, low-fat/high carbohydrate triheptanoin • Ultragenyx acid oxidative Endocrinology replacement 7/31/20 diets, carnitine and medium-chain triglyceride (MCT) oil, a medical food product. oral liquid disorder therapy Revascor • Potentially large impacted population. rexlemestrocel-L • Mesoblast • Chronic heart failure Cardiovascular Stem cell therapy • Proposed for use in left ventricular systolic dysfunction. 2020 intramyocardial injection • Would be reserved for use in patients who had failed multiple other therapies. • Proposed for the treatment of relapsed/refractory disease after at least three prior lines JNJ-68284528 Anti-BCMA CAR-T • Janssen • Multiple myeloma Oncology of therapy. 2020 intravenous infusion therapy • Demonstrated a 100% overall response rate in the Phase I/II CARTITUDE-1 trial. • Proposed for the treatment of relapsed/refractory disease after at least five KTE-X19 • Mantle cell • Gilead Oncology CAR-T therapy prior therapies. 2020 intravenous infusion lymphoma • Demonstrated an overall response rate of 93%, including 67% with complete response. BMN 270 • Proposed for the treatment of adults with severe disease (~60% of the total hemophilia Coagulation valoctocogene roxaparvovec • BioMarin • Hemophilia A Gene therapy A population). 2020 disorders intravenous infusion • Current standard of care is factor VIII replacement therapy or Hemlibra. Ryoncil Immunology / • IV infusion twice weekly for 4 consecutive weeks. • Acute graft vs. remestemcel-L • Mesoblast Autoimmune Stem cell therapy • Among 50 patients who received ≥ 1 treatment infusion, the Day 100 mortality rate was 2020 host disease intravenous infusion disease 22%, in contrast to Day 100 mortality rates as high as 70% in historical controls. JCAR017 • Juno • Non-Hodgkin's • Would be third to market after Kymriah and Yescarta for this indication. lisocabtagene maraleucel Oncology CAR-T therapy 2020 Therapeutics lymphoma • Has demonstrated a relatively favorable adverse effect profile. intravenous infusion AMT-061 • For the treatment of adults with severe disease (~40% of the total hemophilia Coagulation etranacogene dezaparvovec • Uniqure • Hemophilia B Gene therapy B population). 2020-2021 disorders intravenous infusion • Current standard of care is factor IX replacement therapy. NSR-REP1 • Confirmation of diagnosis will be key, as clinical presentation of this disease is similar to • Nightstar • Choroideremia Ophthalmology Gene therapy 2020-2021 subretinal injection other conditions.

SRP-9001 • Duchenne muscular microdystrophin • Sarepta Musculoskeletal Gene therapy • Targets exons 18 through 58 (~60-75% of DMD patients have mutations in these exons). 2020-2021 dystrophy intravenous infusion

Upcoming Specialty Products

Anticipated Drug Name Manufacturer Indication(s) Drug Class Mechanism of Action Comments Approval Date • Would compete with SRP-9001 gene therapy for those with GALGT2 mutations between exons 18 and 58. • Sarepta • Duchenne muscular dystrophy Musculoskeletal Gene therapy • SRP-9001 is further along in the pipeline process, but it’s too 2020-2021 intra-arterial injection early to distinguish between the two agents’ relative safety and efficacy profiles.

SGT-001 • Solid • Development has been marred by safety issues and FDA-applied • Duchenne muscular dystrophy Musculoskeletal Gene therapy 2021 intravenous infusion Biosciences clinical trial holds, with thus far mediocre efficacy results.

• For the treatment of adults with severe disease (~60% of the total SPK-8011 • Spark Coagulation hemophilia A population). • Hemophilia A Gene therapy 2021 intravenous infusion • Roche disorders • Current standard of care is factor VIII replacement therapy or Hemlibra. • Current standard of care is surgery, followed by radiation and Ad-RTS-hIL-12 / veledimex • Ziopharm Gene therapy + oral chemotherapy (usually with temozolomide). intratumoral injection + • Recurrent glioblastoma Oncology 2021-2022 Oncology activator agent • Would potentially be used after resection and oral therapy radiation+temozolomide if progression or recurrence.

Upcoming Non-Specialty Products

Anticipated Drug Name Manufacturer Indication(s) Drug Class Mechanism of Action Comments Approval Date BHV3000 • Would compete with generically available oral triptans rimegepant • Biohaven • Migraine headaches Neurology CGRP antagonist 2/21/20 for the same indication. oral tablets ETC-1002 / Zetia Cholesterol hepatic biosyn- • Proposed for use in those who need additional • Esperion bempedoic acid / ezetimibe • Hyperlipidemia Cardiovascular thesis inhibitor/cholesterol LDL-C lowering despite the use of currently 2/26/20 Therapeutics oral tablets absorption inhibitor accessible therapies. CNS7056 • Sedation during remimazolam • Paion Anesthesia Benzodiazepine derivative • Rapid-acting, short-duration sedative. 4/3/20 gastrointestinal procedures intravenous infusion Ongentys • Proposed for use as an adjunctive treatment to • Neurocrine Catechol-o-methyltransferase opicapone • Parkinson's disease Neurology levodopa/carbidopa in patients experiencing 4/26/20 Biosciences (COMT) inhibitor oral capsules OFF episodes. SEP289 Dopamine and norepinephrine • Once-daily dosing. dasotraline • Sunovion • Binge eating disorder Psychiatry 5/14/20 reuptake inhibitor • Same indication as Vyvanse. oral tablet Amphora L-lactic acid, citric acid and • Maintains an acidic vaginal environment that is • Evofem • Pregnancy prevention Women's health Spermicide 5/25/20 potassium bitartrate inhospitable to sperm. topical therapy VP-102 • Current therapies in use include cryotherapy, scraping • Verrica cantharidin • Molluscum contagiosum Dermatology Vesicant and irritant or cantharidin obtained by provider offices from 7/13/20 Pharmaceuticals topical solution outside sources. Qutenza • Averitas • Diabetic peripheral capsaicin Neurology Substance P depletion • 8% topical patch. 7/13/20 Pharmaceuticals neuropathy topical patch RVL-1201 • Vertical Alpha-adrenergic receptor • Once-daily ophthalmic formulation. oxymetazoline • Blepharoptosis Ophthalmology 7/16/20 Pharmaceuticals agonist • Standard of care is surgery for severe cases. ophthalmic solution Viaskin Peanut • Proposed for treatment of children 4-11 years old. Epicutaneous desensitization peanut antigen • DBV Technologies • Peanut hypersensitivity Immunology • Once daily patch. 8/5/20 therapy transdermal patch • Would compete with Palforzia. TRC101 • Metabolic acidosis in Non-absorbable hydrochlo- • Currently there are no FDA-approved chronic therapies veverimer • Tricida patients with chronic Kidney disease 8/22/20 ride-binding polymer agent for treating metabolic acidosis. oral suspension kidney disease (CKD) Winlevi • Unlike oral hormonal therapies for acne, this therapy clascoterone • Cassiopea • Acne vulgaris Dermatology Dihydrotesterone antagonist 8/27/20 may be used in both male and female patients. topical cream SPN-812 • Attention deficit • Supernus Serotonin norepinephrine viloxazine hyperactivity disorder Psychiatry • Multiple other therapies for ADHD already exist. 11/8/20 Pharmaceuticals modulating agent (SNMA) oral therapy (ADHD) © 2020 Envolve. All rights reserved. Page 6 of 9 Pipeline Report Biosimilars February 2020

Biosimilars

Status / Estimated Biosimilar Currently Drug Name Manufacturer Biosimilar Reference Drug Indication(s) Drug Class Comments Approval Launched?

• Rheumatoid arthritis • Crohn's disease Avsola • Ulcerative colitis Yes - • Another biosimilar to Remicade, after infliximab-axxq • Amgen Remicade Immunology FDA-approved • Plaque psoriasis Inflectra, Renflexis Inflectra and Renflexis. intravenous infusion • Psoriatic arthritis • Ankylosing spondylitis SB8 BLA is under • Samsung Bioepis Yes - • Another biosimilar to Avastin, after bevacizumab biosimilar Avastin • Breast cancer Oncology FDA review; • Merck Mvasi, Zirabev Mvasi, Zirabev. intravenous infusion BSUFA date Q4 2020

Generic Specialty Agents - Recent Approvals

Generic Name Brand Name Manufacturer Market Launch Date

deferasirox Jadenu • Alembic 11/22/19 everolimus Afinitor (2.5 mg, 5 mg, 7.5 mg) • Par 12/10/19 penicillamine Depen • Par 1/2/20

Generic Specialty Agents - Pipeline Agents

Generic Name Brand Name Manufacturer Anticipated Launch Date

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 abiraterone acetate Zytiga (500 mg) • Teva 2020 thalidomide Thalomid • Lannett 2020 tolvaptan Samsca • Par 2020 • Mylan • Sandoz dimethyl fumarate Tecfidera • Teva 2020-2021 • Graviti Pharmaceuticals • Macleods Pharmaceuticals

Generic Non-Specialty Agents - Recent Approvals

Generic Name Brand Name Manufacturer Market Launch Date

mesalamine Apriso • Mylan 11/27/19 chlorzoxazone Lorzone • Novitium 11/27/19 sucralfate Carafate oral suspension • Amneal 12/3/19 ethinyl estradiol / etonorgestrel NuvaRing • Amneal 12/12/19 doxepin hydrochloride Silenor • Macoven Pharmaceuticals 12/16/19 travoprost Travatan Z • Mylan 12/18/19 dapsone Aczone 7.5% • Taro 1/2/20 insulin aspart recombinant Novolog vial, FlexPen • Novo Nordisk 1/2/20 insulin aspart protamine recombinant, insulin aspart recombinant Novolog Mix 70/30 vial, PenFill • Novo Nordisk 1/2/20 budesonide / formoterol fumarate dihydrate Symbicort • Prasco 1/6/20 naloxone hydrochloride Evzio • IJ Therapeutics 1/13/20

Generic Non-Specialty Agents - Pipeline Agents

Generic Name Brand Name Manufacturer Anticipated Launch Date

• Sandoz • Wockhardt acetaminophen Ofirmev 12/6/20 • Aurobindo • Custopharm • Actavis methylphenidate Aptensio XR 2020 • Teva meloxicam Vivlodex • Lupin 2020