Drug Pipeline Monthly Update

Critical updates in an ever changing environment

September 2017

New drug information

●● Zerviate™ (cetirizine ophthalmic solution): The U.S. Food and Drug Administration (FDA) approved Nicox Ophthalmic’s Zerviate for the twice daily treatment of ocular itching associated with allergic conjunctivitis.

●● Benznidazole Tablets: The FDA granted accelerated approval to Chemo Research’s Benznidazole Tablets for the treatment of Chagas disease (American trypanosomiasis) caused by Trypanosoma cruzi in pediatric patients 2 to 12 years of age. Prior to approval, this drug was only available through the Centers for Disease Control and Prevention. The Chemo group worked with its U.S.-based pharmaceutical division Exeltis, as well as Mundo Sano and Drugs for Neglected Diseases initiative (DNDi) to complete the New Drug Application and notes that a substantial part of any revenue derived from the future sale of the neglected tropical disease priority review voucher they received will be directed towards enhancing access to treatment for Chagas patients and improving patient health in other disease areas.1

●● Zypitamag™ (pitavastatin magnesium): Zydus Pharmaceuticals received FDA approval for Zypitamag for high cholesterol. Zypitamag is an alternate salt product of Kowa Company Ltd’s Livalo® (pitastatin calcium).

●● Admelog® (insulin lispro injection): The FDA granted tentative approval for Sanofi’s Admelog for the treatment of adults and children with diabetes mellitus. Tentative approval from the FDA means that Admelog met all necessary regulatory requirements for approval in the United States, pending any patent issues yet to be resolved.

●● Adzenys™ ER (amphetamine): Neos Therapeutics received FDA approval of Adzenys ER, amphetamine extended-release oral suspension for the treatment of attention deficit hyperactivity disorder (ADHD) in patients aged 6 years and older. Adzenys ER is considered bioequivalent to Shire’s Adderall® XR.

●● Trelegy™ Ellipta® (fluticasone furoate, umeclidinium and vilanterol): GlaxoSmithKline and Innoviva received FDA approval of Trelegy Ellipta, a triple drug combination inhaler for the long-term, once-daily maintenance treatment of appropriate patients with chronic obstructive pulmonary disease (COPD), including chronic bronchitis and/or emphysema. Trelegy Ellipta is the first inhaler to contain the combination of three drug classes in one inhaler: an inhaled corticosteroid, an anticholinergic, and a long-acting beta2-adrenergic agonist.

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. Drug Pipeline Monthly Update: September 2017 Page 2

Generic Drug Information

●● Sabril® (vigabatrin): Par Pharmaceuticals launched the first generic of Lundbeck’s Sabril, an adjunctive therapy for refractory complex partial seizures and a monotherapy for pediatric patients with infantile spasms. No patents or exclusivities remain. According to IMS, Sabril had approximately $329 million in U.S. sales over the past year.

●● Fosrenol® (lanthanum): Natco Pharma/Lupin pharmaceuticals launched the first generic of Shire’s Fosrenol to reduce serum phosphate in patients with end stage renal disease (ESRD). Multiple manufacturers are awaiting FDA approval of their generic tablets. According to IMS, Fosrenol had $122.4 million in U.S. sales over the past year. Drug Pipeline Monthly Update: September 2017 Page 3

New molecular entity approvals in the past 12 months

Generic name Brand name Manufacturer Indication(s) Date approved* benznidazole Benznidazole Chemo Research/ Chagas disease August 2017 Tablets DNDi/Mundo Sano betrixaban Bevyxxa™ Portola Prophylaxis of venous thromboembolism July 2017

delafloxacin Baxdela™ Melinta Skin infections June 2017

naldemedine Symproic® Shionogi Pain March 2017

safinamide Xadago® Newron Parkinson’s disease March 2017 Pharmaceuticals desmopressin nasal spray Noctiva™ Allergan and Serenity Nocturnal polyuria March 2017

house dust mite sublingual Odactra™ Merck, Sharp & House dust mite allergies March 2017 allergy immunotherapy Dohme plecanatide Trulance™ Synergy Chronic idiopathic constipation January 2017

crisaborole Eucrisa™ Pfizer/Anacor Mild to moderate atopic dermatitis December 2016

prasterone Intrarosa® Endoceutics Inc Pain during intercourse November 2016

*Date indicates FDA approval date only. The product launch and marketing dates are determined by the approved product’s manufacturer. Drug Pipeline Monthly Update: September 2017 Page 4

Other new product approvals in the past twelve months

Generic name Brand name Manufacturer Indication(s) Date approved* fluticasone furoate, Trelegy™ Ellipta® GSK/Innoviva COPD September 2017 umeclidinium, vilanterol amphetamine extended release Adzenys™ ER Neos Therapeutics ADHD September 2017 suspension insulin lispro Admelog® Sanofi Diabetes August 2017

lesinurad/allopurinol Duzallo™ Ironwood Uncontrolled gout August 2017 Pharmaceuticals pitavastatin sodium Nikita™ Lupin High cholesterol August 2017

beclomethasone dipropionate Qvar® RediHaler™ Teva Teva August 2017

insulin glargine Lusduna® Nexvue™ Merck Diabetes August 2017

methylphenidate extended- Cotempla™ XR-ODT Neos Therapeutics ADHD July 2017 release orally disintegrating tablets mixed salts of a single-entity Mydayis™ Shire ADHD July 2017 amphetamine products pitavastatin Zipitamag Zydus High cholesterol July 2017

epinephrine injection Symjepi™ Adamis Allergic reactions June 2017 Pharmaceuticals Corporation cetirizine ophthalmic solution Zerviate™ Nicox Ophthalmic Eye itching May 2017

methotrexate solution Xatmep™ Silvergate ALL and arthritis in pediatric patients April 2017 Pharmaceuticals oxycodone, immediate-release RoxyBond™ Inspirion/ Pain, abuse deterrent April 2017 Daiichi Sankyo dapagliflozin/saxagliptin Qtern™ AstraZeneca Diabetes February 2016

lisdexamfetamine (chew tab) Vyvanse® Shire ADHD February 2017

naloxone nasal spray, 2 mg Narcan® Adapt Pharma Inc Opioid overdose January 2016

fluticasone propionate ArmonAir™ Teva Asthma January 2016 RespiClick® fluticasone AirDuo™ Teva Asthma January 2016 propionate/salmeterol RespiClick® oxymetazoline Rhofade™ Allergan Rosacea January 2016

hydrocodone extended release Vantrela™ ER Teva Pain, abuse deterrent January 2016

morphine extended release Arymo™ ER Egalet Pain, abuse deterrent January 2016

insulin glargine Basaglar™ Eli Lilly Diabetes December 2015, launched in December 2016 empagliflozin/metformin Synjardy® XR Eli Lilly Diabetes December 2016 extended release Lantus® (insulin glargine)/ Soliqua™ Sanofi Diabetes November 2016 Adlyxin™ (lixisenatide) Tresiba® (insulin degludec/ Xultophy® Novo Nordisk Diabetes November 2016 Victoza® (liraglutide) Drug Pipeline Monthly Update: September 2017 Page 5

Other new product approvals in the past twelve months contined

Generic name Brand name Manufacturer Indication(s) Date approved* doxylamine/pyridoxine XR Bonjesta® Duchesnay Pregnancy-related nausea and vomiting November 2016

tenofovir alafenamide Vemlidy® Gilead Hepatitis B November 2016

mebendazole Vermox® Johnson & Johnson/ Parasitic disease November 2016 Janssen norethindrone/estradiol fe Taytulla™ Apil Pregnancy prevention October 2016

sumatriptan/naproxen Treximet® Permix Migraine October 2016

*Date indicates FDA approval date only. The product launch and marketing dates are determined by the approved product’s manufacturer.

Pipeline watch Anticipated FDA Generic name Brand name Manufacturer Indication(s) decision date ITCA 650 (exenatide mini-pump) N/A Intarcia Diabetes September 2017

secnidazole Solosec™ Symbiomix Bacterial vaginosis September 2017

insulin aspart FIAsp™ Novo Nordisk Diabetes September 2017

tadalafil PharmFilm® N/A MonoSol RX ED September 2017

aripiprazole, digital tablet Abilify® Otsuka, Proteus Health Drug/device combo for schizophrenia, 4th Quarter 2017 bipolar disorder and major depression testosterone enanthate Xyosted™ Antares Testosterone replacement October 2017 auto-injector QuickShot™ Pharmaceuticals rolapitant N/A Tesaro, Opko Health Chemotherapy-induced nausea and October 2017 vomiting aprepitant Cinvanti™ Heron Therapeutics Chemotherapy-induced nausea and November 2017 vomiting buprenorphine monthly depot N/A Indivior Opioid use disorder November 2017

semaglutide N/A Novo Nordisk Diabetes December 2017

ertugliflozin N/A Merck/Pfizer Diabetes December 2017

ertugliflozin/metformin N/A Merck/Pfizer Diabetes December 2017

ertugliflozin/sitagliptin N/A Merck/Pfizer Diabetes December 2017

acetaminophen/ibuprofen Maxigesic® AFT Pharmaceuticals Pain December 2017

SUN-101/eFlow (glycopyrrolate) N/A Sunovion COPD December 2017 Pharmaceuticals Inc dolutegravir/rilpivirine N/A Viiv Healthcare HIV-1 infection December 2017

ethinyl estradiol/ Twirla™ Agile Therapeutics Pregnancy prevention December 2017 levonorgestrel transdermal Drug Pipeline Monthly Update: September 2017 Page 6

Pipeline watch contined Anticipated FDA Generic name Brand name Manufacturer Indication(s) decision date testosterone undecanoate Jatenzo™ Clarus Therapeutics Testosterone replacement December 2017

mometasone furoate sinus Sinuva™ Intersect ENT Chronic sinusitis January 2017 implant buprenorphine FluidCrystal® N/A Braeburn Opioid use disorder January 2018 Pharmaceuticals polyethylene glycol and Plenvu™ Salix and Norgine Bowel cleansing February 2018 ascorbate andexanet alfa AndexXa™ Portola Anticoagulant reversal agent February 2018

LPCN 1021 (testosterone) N/A Lipocine Testosterone replacement February 2018

bictegravir/emtricitabine/ N/A Gilead HIV-1 infection February 2018 tenofovir alafenamide netarsudil Rhopressa™ Aerie Pharmaceuticals Glaucoma or ocular hypertension February 2018

First generic approvals of top selling brand-name drugs in the past twelve months

Generic name Brand name Manufacturer Indication(s) Approval date* prasugrel Effient® Eli Lilly/Daiichi Reduction of CV events August 2017 Sankyo eletriptan Relpax® Pfizer Migraine August 2017

mesalamine delayed release Lialda® Zydus Ulcerative colitis August 2017

moxifloxacin ophthalmic solution Vigamox® Apotex Eye infection July 2017

testosterone topical transdermal Axiron® Lilly Testosterone replacement July 2017 solution atomoxetine Strattera® Eli Lilly ADHD June 2017

ezetimibe/simvastatin Vytorin® Merck/Schering- High cholesterol May 2017 Plough desvenlafaxine SR Pristiq® Pfizer Depression March 2017

methylphenidate ER Concerta® Janssen ADHD January 2017

oseltamivir phosphate capsules Tamiflu® Roche/Genetech Influenza December 2016

ezetimibe Zetia® Merck High cholesterol December 2016

olmesartan and olmesartan/ Benicar®/ Daiichi-Sankyo High blood pressure November 2016 HCTZ Benicar® HCT quetiapine XR Seroquel XR® AstraZeneca Schizophrenia/Bipolar disorder November 2016

*Date usually indicates FDA approval date. The product’s launch date is determined by the manufacturer. Generic approvals that do not come to market within three months of approval are listed and dated when they enter the market. Drug Pipeline Monthly Update: September 2017 Page 7

Other first generic launches in the past twelve months

Generic name Brand name Manufacturer Indication(s) Date approved* adapalene/benzoyl peroxide Epiduo® Galderma Acne August 2017 scopolamine Transderm-Scop® Sandoz, Baxter Motion sickness August 2017 Healthcare, Glaxo Consumer Healthcare sevelamer carbonate Renvela® Genzyme Control serum phosphorus August 2017 melphalan Alkeran® Apo Pharma Multiple myeloma/epithelial July 2017 carcinoma of the ovary olopatadine solution Pataday® Teva Eye itching June 2017 thyroid tab Armour Thyroid® Actavis Hypothyroid June 2017 desoximetasone ointment Topicort® Taro Skin conditions May 2017 tazarotene cream Tazorac® Allergan Plaque psoriasis and acne April 2017 levonorgestrel/ethinyl estradiol Quartette® Teva Pregnancy prevention April 2017 venlafaxine extended-release Venlafaxine ER® UCB Pharma/Vertical Depression and anxiety April 2017 Pharmaceuticals zileuton extended-release Zyflo CR® Chiesi USA Asthma April 2017 prednisolone sodium phosphate Millipred® Zylera Pharmaceuticals Inflammatory conditions March 2017 oral solution 10 mg/5 mL prednisolone sodium phosphate Veripred® 20 Zylera Pharmaceuticals Inflammatory conditions March 2017 oral solution 20mg/5mL methylphenidate SR 60 mg Ritalin® LA Novartis ADHD March 2017 flurandrenolide oint Cordran® Aqua Pharmaceuticals Skin irritation February 2017 lopinavir/ritonavir soln Kaletra® AbbVie HIV January 2017 aspirin/dipyridamole Aggrenox® Boehringer Ingelheim Reduce risk of stroke January 2017 dexmethylphenidate Focalin XR® Novartis ADHD January 2017 rasagiline Azilect® Teva Neuroscience Parkinson’s disease January 2017 aprepitant Emend® Merck/Schering-Plough Chemotherapy induced nausea/ January 2017 vomiting epinephrine injection, Authorized generic of Mylan Anaphylaxis December 2016 USP auto-injection Epipen® and Epipen Jr® Auto-Injector bimatoprost Latisse® Allergan Dermatologics Eyelash growth December 2016 armodafinil Nuvigil® Cephalon Improve wakefulness in patients with November 2016 excessive sleepiness associated certain disorders fluoxetine tablets Sarafem® Actavis Premenstrual dysphoric disorder November 2016 olmesartan/amlodipine/ Tribenzor® Daiichi Sankyo Hypertension November 2016 hydrochlorothiazide amlodipine/olmesartan Azor® Daiichi Sankyo Hypertension November 2016 hydromorphone XR Exalgo® Mallinckrodt Brand Pain October 2016 Pharma Yuvafem® (estradiol vaginal tab) Vagifem® Novo Nordisk Vaginitis October 2016 flurandrenolide lotion Cordran® Aqua Pharmaceuticals Eczema October 2016 *Date usually indicates FDA approval date. The product’s launch date is determined by the manufacturer. Generic approvals that do not come to market within three months of approval are listed and dated when they enter the market. Drug Pipeline Monthly Update: September 2017 Page 8

Generics of top selling brand drugs potentially available soon

Generic name Brand name Manufacturer Indication(s) To market date* oseltamivir phosphate suspension Tamiflu® Roche/Genentech Influenza 2017

buprenorphine Butrans Purdue Pain October 2017

exenatide Byetta® AstraZeneca Diabetes October 2017

tadalafil Adcirca Eli Lilly PAH November 2017

sildenafil citrate Viagra® Pfizer ED December 2017

tenofovir disoproxil fumarate Viread Gilead HIV/HBV December 2017– January 2018 tadalafil Cialis® Lilly ED 2018

glatiramer acetate 40 mg/mL Copaxone® Teva Multiple sclerosis 2017-2018

ethinyl estradiol/etonogestrel NuvaRing® Organon/Merck & Co Pregnancy prevention April 2018

testosterone Androgel® AbbVie Testosterone 2018 (1.62%) replacement loteprednol Lotemax® Bausch + Lomb/Valeant Eye inflammation 2018

difluprednate Durezol® Alcon/Novartis Eye inflammation January 2018

ganirelix acetate Ganirelix® Organon/Merck & Co Infertility January 2018

memantine extended release Namenda XR Forest/Allergan Alzheimer’s disease First half 2018

*Expected to market dates are predictions made by Prime Therapeutics based on industry information.

References 1. https://www.dndi.org/2017/media-centre/press-releases/fda-approves-benznidazole-chagas-children/

All brand names are property of their respective owners.

2992-A1 © Prime Therapeutics LLC 09/17