Drug Pipeline Update

D Drug Insights > June 2016

→ New drug information → Generic drug information

●● Probuphine® (buprenorphine implant): The Food and ●● Glyset® (miglitol): Pfizer’s Glyset, used to treat type 2 Drug Administration (FDA) approved Braeburn and diabetes mellitus, is now available generically. Titan’s Probuphine, the first buprenorphine implant for ●● Doryx® (doxycycline hyclate delayed-release): There is the maintenance treatment of opioid dependence. now a generic version of Mayne Pharma’s Doryx tablets Probuphine provides a constant, low-level dose of for a wide variety of bacterial infections. According to buprenorphine for six months. IMS, Doryx had approximately $182 million in annual ●● Byvalson™ (nebivolol/valsartan): Allergan received FDA U.S. sales. approval for Byvalson for the treatment of high blood ●● Nuvigil® (armodafanil): Mylan launched the first generic pressure. Byvalson, is a fixed-dose combination of two version of Cephalon’s Nuvigil, used to improve FDA-approved blood pressure lowering agents, Bystolic® wakefulness, with 180 days of exclusivity. According to (nebivolol) and valsartan. IMS, Nuvigil had approximately $437 million in annual ●● Jentadueto® XR (linagliptin and metformin U.S. sales. hydrochloride extended-release): The FDA approved ●● Tikosyn® (dofetilade): There is now a generic version of Boehringer Ingelheim and Lilly’s extended release Pfizer’s Tikosyn capsules for the maintenance of normal formulation of Jentadueto for the treatment of type 2 sinus rhythm. Tikosyn converts atrial fibrillation and diabetes in adults. atrial flutter to normal sinus rhythm. Mayne Pharma will ●● Rayaldee® (calcifediol extended-release): The FDA have 180 days of exclusivity. According to IMS, Tikosyn approved OPKO Healths’ Rayaldee capsules for the had approximately $150 million in annual U.S. sales. treatment of secondary hyperparathyroidism associated ●● Makena® (hydroxyprogesterone caproate): There is now with vitamin D insufficiency in stage 3-4 chronic a generic version of Amag Pharmaceuticals’ and kidney disease. Lumara’s Makena for the prevention of preterm labor. ●● Gonitro™ (nitroglycerin sublingual powder): Espero Pharmaeuticals received FDA approval of Gonitro for the treatment of acute relief of an attack or prophylaxis of angina pectoris due to coronary artery disease.

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 > June 2016 Page 2

New molecular entity approvals in the past twelve months

Generic name Brand name Manufacturer Indication(s) Date approved* pimavanserin Nuplazid™ Acadia Psychosis associated with April 2016 Parkinson's disease brivaracetam Briviact® UCB Seizure February 2016

glycopyrronium Seebri™ Neohaler Novartis COPD November 2015

glycopyrronium/indacaterol Utibron™ Neohaler Novartis COPD November 2015

patiromer Veltassa™ Relypsa High potassium October 2015

insulin degludec/insulin aspart Ryzodeg™ Novo Nordisk Diabetes October 2015

insulin degludec Tresiba™ Novo Nordisk Diabetes October 2015

cariprazine Vraylar™ Allergan Bipolar and schizophrenia September 2015

rolapitant Varubi™ Tesaro Prevention and treatment of September 2015 chemotherapy induced nausea and vomiting flibanserin Addyi™ Sprout Pharmaceuticals Hypoactive sexual desire disorder August 2015 (women) sacubitril/valsartan Entresto™ Novartis Heart failure July 2015

brexpiprazole Rexulti™ Otsuka/Lundbeck Schizophrenia/depression July 2015

*Date indicates FDA approval date only. The product launch and marketing dates are determined by the approved product’s manufacturer. Drug Pipeline > June 2016 Page 3

Other new product approvals in the past twelve months

Generic name Brand name Manufacturer Indication(s) Date approved* calcifediol ER Rayaldee® OPKO Health Chronic kidney disease and June 2016 vitamin D insufficiency nitroglycerin sublingual powder Gonitro™ Espero Pharmaeuticals Relief of angina pectoris June 2016

nebivolol/valsartan Byvalson™ Allergan Hypertension June 2016

linagliptin/metformin Jentadueto XR® Boehringer Ingelheim and Diabetes May 2016 Lilly buprenorphine implant Probuphine® Braeburn and Titan Maintenance treatment of opioid May 2016 dependence oxycodone ER Xtampza™ Collegium Chronic pain May 2016

glycopyrrolate/formoterol Bevespi™ AstraZeneca COPD May 2016 Aerosphere bromfenac 0.075% BromSite™ InSite Vision Inflammation and pain associated April 2016 with cataract surgery sumatriptan succinate injection Zembrace™ Dr. Reddy’s Migraine February 2016 SymTouch™ sumatriptan, intranasal powder Onzetra™ Xsail™ Avanir and Optinose Migraine February 2016

lesinurad Zurampic™ AstraZeneca Gout January 2016

amphetamine extended-release Adzenys XR-ODT™ Neos Therapeutics ADHD January 2016 ODT insulin human injection Humulin® R Lilly Diabetes January 2016 U-500 KwikPen methylphenidate extended-release QuilliChew™ ER Pfizer ADHD December 2015

insulin glargine Basaglar™ Lilly Diabetes December 2015

naloxone Narcan® Adapt Pharma/ Opioid overdose November 2015 Lightlake Therapeutics calcipotriene/betamethasone, Enstilar® Leo Pharma Plaque psoriasis November 2015 aerosol foam meloxicam Vivlodex™ Iroko Pain October 2015

amphetamine Dynavel™ XR Tris Pharma ADHD October 2015

buprenorphine buccal film Belbuca™ Endo, Biodelivery Sciences Pain October 2015

aripiprazole lauroxil Aristada™ Alkermes Schizophrenia October 2015

morphine ER MorphaBond™ ER Inspirion Delivery Pain (abuse deterrent) October 2015

aspirin, extended-release Durlaza™ New Haven Pharmaceuticals Cardiovascular prevention September 2015

empagliflozin and metformin Synjardy™ Boehringer Ingelheim Diabetes August 2015

levetiracetam Spritam™ Aprecia Seizures August 2015

tacrolimus Envarsus® XR Veloxis Pharma Prophylaxis of rejection in kidney July 2015 transplant *Date indicates FDA approval date only. The product launch and marketing dates are determined by the approved product’s manufacturer. Drug Pipeline > June 2016 Page 4

Pipeline watch Anticipated FDA Generic name Brand name Manufacturer Indication(s) decision date istradefylline N/A Kyowa Kirin Parkinson’s disease June 2016

testosterone N/A Lipocine Replacement therapy June 2016

N/A Amphora™ Evofem Pregnancy prevention July 2016

lorcaserin Belviq™ XR Arena Weight loss July 2016

dronabinol oral solution Syndros® Insys Therapeutics Cachexia July 2016

methylnaltrexone oral Relistor® Valeant Opioid-induced constipation July 2016

lixisenatide Lyxumia™ Sanofi Diabetes July 2016

latanoprostene bunod Vesneo™ Bausch & Lomb/Valeant Glaucoma July 2016

lifitegrast N/A Shire Dry eye disease July 2016

insulin degludec and liraglutide Xultophy® Novo Nordisk Diabetes July 2016

lixisenatide/insulin glargine LixiLan™ Sanofi Diabetes August 2016

abametapir Xeglyze™ Hatchtech Head lice September 2016

aspirin/omeprazole Yosprala™ Pozen For secondary prevention of CV September 2016 disease in patients with high risk for ASA-induced ulcers oxycodone, controlled-release Remoxy® Pain Therapeutics and Pain, abuse deterrent September 2016 Durect insulin aspart N/A NovoNordisk Diabetes October 2016

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

cetirizine ophthalmic N/A Nicox Ophthalmics Allergic conjunctivitis October 2016

oxymetazoline HCl cream 1.0% N/A Allergan Rosacea October 2016 Drug Pipeline > June 2016 Page 5

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

Generic name Brand name Brand manufacturer Indication(s) Date approved* rosuvastatin Crestor® AstraZeneca High cholesterol April 2016

mometasone nasal spray Nasonex® Merck Seasonal allergies March 2016

imatinib Gleevec® Novartis Cancer (multiple indications) February 2016

dutasteride Avodart® GlaxoSmithKline BPH October 2015

memantine Namenda® Actavis Alzheimer’s disease July 2015

glatiramer Glatopa™ Teva Relapsing-remitting multiple June 2015 sclerosis *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 > June 2016 Page 6

Other first generic approvals in the past twelve months Generic name Brand name Brand manufacturer Indication(s) Date approved* hydroxyprogesterone Makena® Amag and Lumara Reduce preterm birth June 2016 dofetilide Tikosyn® Pfizer Irregular heartbeats June 2016 armodafanil Nuvigil® Cephalon Improve wakefulness June 2016 doxycyline hclate DR Doryx® Mayne Severe acne June 2016 miglitol Glyset® Pfizer Diabetes June 2016 hydrocodone-acetaminophen solution Zamicet Beach Pain May 2016 benzphetamine Regimex® Wraser Pharmaceuticals Weight loss May 2016 flurandrenolide cream Cordran® Aqua Pharmaceuticals Dermatoses April 2016 diclofenac sodium gel, 1% Voltaren® Gel Endo Osteoarthritis March 2016 frovatriptan tab Frova® Endo Migraines March 2016 zolpidem sublingual tablets Intermezzo® Purdue Insomnia March 2016 darifenacin 24 hr SR tabs Enablex® Actavis Overactive bladder March 2016 oxiconazole cream, 1% Oxistat® cream Pharmaderm Fungal infection March 2016 cyclopentolate ophthalmic solution, 0.5% Cyclogyl® 0.5% Alcon To produce mydriasis and March 2016 cycloplegia naftifine cream, 2% Naftin® Merz Pharmaceuticals Fungal infection February 2016 metformin modified release 24hr SR Glumetza ® Valeant Diabetes February 2016 norgestimate/ethinyl estradiol Ortho Tri-Cyclen Lo® Jannsen Contraceptive January 2016 linezolid suspension Zyvox® Pfizer Treatment of bacterial December 2015 infection repaglinide/metformin Prandimet™ NovoNordisk Diabetes December 2015 dutasteride/tamsulosin Jalyn® GlaxoSmithKline BPH December 2015 trimipramine Surmontil® Teva Antidepressant November 2015 nevirapine ER Viramune® XR Boehringer Ingelheim HIV November 2015 paliperidone ER Invega® Janssen Schizophrenia October 2015 fluvastatin Lescol® XL Novartis High cholesterol October 2015 testosterone transdermal gel, 1% Androgel® AbbVie Low testosterone October 2015 pimozide Orap® Teva Tourette’s disorder October 2015 methyltestosterone Testred® and Valeant Hormone replacement October 2015 Android® memantine oral solution Namenda® Actavis Alzheimer’s disease October 2015 rivastigmine TD patch Exelon® TD patch Novartis Alzheimer’s disease September 2015 tretinoin gel, 0.05% Atralin® Valeant Acne September 2015 naproxen SR 24hr Naprelan® SR Almatica and Shionogi Pain September 2015 Pharma tetrabenazine Xenazine® Lundbeck Chorea associated with August 2015 Huntington’s disease pramipexole extended-release Mirapex® Boehringer Ingelheim Parkinson’s disease August 2015 phenoxybenzamine Dibenzyline® Concordia Pheochromocytoma August 2015 acetaminophen/caffeine/dihydrocodeine Trezix® Wraser Pharmaceuticals Pain August 2015 megestrol acetate suspension Megace® ES Par Treatment of appetite loss August 2015

continued Drug Pipeline > June 2016 Page 7

Other first generic approvals in the past twelve months (continued) Generic name Brand name Brand manufacturer Indication(s) Date approved* budesonide inhalation susp, 1 mg/2 mL Pulmicort® Respules AstraZeneca Respiratory August 2015 almotriptan Axert® Jannsen Migraine July 2015 pyridostigmine bromide Mestinon® Timespan Valeant Myasthenia gravis July 2015 bexarotene Targretin® Valeant Cutaneous t-cell lymphoma July 2015

* 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.

Generics of top selling brand drugs potentially available soon

Generic name Brand name Brand manufacturer Indication(s) To market date* olmesartan and olmesartan/HCTZ Benicar®/ Daiichi-Sankyo High blood pressure October 2016 Benicar® HCT quetiapine XR Seroquel XR® AstraZeneca Schizophrenia/bipolar November 2016 disorder ezetimibe Zetia® Merck High cholesterol December 2016

eletriptan Relpax® Pfizer Migraines December 2016

glatiramer acetate Copaxone Teva Relapsing forms of multiple 4Q2016 40 mg/ml sclerosis sildenafil Viagra® Pfizer Erectile dysfunction Approved March 2016; launch anticipated December 2016 *Expected launch dates are predictions made by Prime Therapeutics based on industry information. 03002671

2992-A1 © Prime Therapeutics LLC 06/16