Drug Pipeline Monthly Update Critical updates in an ever changing environment December 2018 New drug information ● Temixys™ (lamivudine/tenofovir disoproxil fumarate): The Food and Drug Administration (FDA) approved Celltrion’s Temixys in combination with other antiretroviral agents for the treatment of HIV-1 infection in adults and pediatric patients weighing at least 35 kg, dosed once daily. Temixys is a combination of two nucleoside reverse transcriptase inhibitors (NRTIs) in one tablet. Celltrion intends to sell Temixys at a discounted price compared to Gilead’s Truvada® (emtricitabine/tenofovir disoproxil fumarate).1 Celltrion plans to launch early 2019.1 ● Tolsura™ (itraconazole) capsules: Mayne Pharma received FDA approval for Tolsura for the treatment of systemic fungal infections in adult patients including certain forms of: → blastomycosis, → histoplasmosis, and → aspergillosis Mayne notes that this is a Super-BioAvailable (SUBA) formulation of itraconazole that has been shown in clinical studies to have increased bioavailability and reduced variability when compared to other itraconazole formulations.2 Tolsura will launch in January 2019.2 ● Montegrity™ (prucalopride): The FDA approved Shire’s Montegrity, a once daily, oral medication for the treatment of adults with chronic idiopathic constipation (CIC). Montegrity will compete for market share in the CIC space with Allergan’s Linzess® (linaclotide), Takeda’s Amitiza® (lubiprostone), and Synergy’s Trulance® (plecanatide). Montegrity is anticipated to launch in 2019. continued 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: December 2018 Page 2 Generic drug information ● Fortesta® (testosterone transdermal gel pump): Actavis Pharma launched the first true generic of Endo Pharmaceuticals’ Fortesta gel pump. Fortesta is indicated in males for testosterone replacement therapy. Fortesta gel pump generated < $10 million in U.S. annual sales in 2017. ● Harvoni® (edipasvir/sofosbuvir): Asegua Therapeutics/Gilead launched an authorized generic for Gilead Science’s Harvoni that is indicated for the treatment of: → chronic hepatitis C virus (HCV) in adults with genotype 1, 4, 5, or 6 infections without cirrhosis or with compensated cirrhosis; → adults with genotype 1 infection with decompensated cirrhosis, in combination with ribavirin; → adults with genotype 1 or 4 infection who are liver transplant recipients without cirrhosis or with compensated cirrhosis, in combination with ribavirin; and → pediatric patients 12 years of age and older or weighing at least 35 kg with genotype 1, 4, 5, or 6 without cirrhosis or with compensated cirrhosis. Harvoni generated $5,549 million in U.S. annual sales in 2017. ● Epclusa® (sofosbuvir/velpatasvir): Asegua Therapeutics/Gilead launched an authorized generic of Gilead Science’s Epclusa for adult patients with chronic HCV genotype 1, 2, 3, 4, 5, or 6 infections: → without cirrhosis or with compensated cirrhosis; → with decompensated cirrhosis for use in combination with ribavirin. Epclusa is expected to be protected from additional generic competition until 2032. Epclusa generated $2,747 million in U.S. annual sales in 2017. ● Zytiga® (abiraterone): Teva Pharmaceuticals, Hikma, and Mylan launched their generic versions of Janssen Biotech’s Zytiga 250 mg tablet which is indicated in combination with prednisone for the treatment of patients with: → metastatic castration-resistant prostate cancer (CRPC); and → metastatic high-risk castration-sensitive prostate cancer (CSPC). Teva, Hikma, and Mylan have shared 180-day exclusivity. Patriot launched an authorized generic version of Zytiga 250 mg. Zytiga 500 mg tablets are not available generically. Zytiga generated $1,224 million in U.S. in 2017. ● Epipen® (epinephrine auto-injector): Teva Pharmaceuticals launched the first true generic version of Mylan Specialty’s Epipen 0.3 mg auto-injector indicated for the emergency treatment of allergic reactions (Type I) including anaphylaxis. Epipen had annual U.S. sales of $763 million in 2017. ● Rapaflo® (silodosin): Sandoz launched the first generic version of Allergan’s Rapaflo capsule for the treatment of the signs and symptoms of benign prostatic hyperplasia (BPH). Multiple manufacturers have since launched their generic versions of Rapaflo. Rapaflo brand generated $206 million in U.S. sales in 2017. ● Amicar® (aminocaproic acid): Vitruvias Therapeutics launched the first true generic of Clover Pharmaceuticals’ Amicar tablet 1000 mg indicated to enhance hemostasis when fibrinolysis contributes to bleeding. Amicar generated $53 million in annual U.S. sales in 2017. Drug Pipeline Monthly Update: December 2018 Page 3 New molecular entity approvals in the past twelve months Generic name Brand name Manufacturer Indication(s) Date approved* prucalopride Montegrity™ Shire CIC December 2018 rifamycin Aemcolo™ Cosmo Travelers’ diarrhea November 2018 Pharmaceuticals revefenacin Yupelri™ AcelRx COPD November 2018 Pharmaceuticals baloxavir marboxil Xofluza™ Shinogi & Co Influenza October 2018 omadacycline Nuzyra™ Paratek Pneumonia and skin infections October 2018 Pharmaceuticals sarecycline Seysara™ Allergan and Paratek Acne October 2018 Pharmaceuticals galcanezumab-gnlm Emgality™ Eli Lilly Prevention of migraine September 2018 fremanezumab-vfrm Ajovy™ Teva Prevention of migraine September 2018 doravirine Pifeltro™ Merck HIV September 2018 eravacycline Xerava™ Tetraphase Pharma Complicated intra-abdominal infections September 2018 segesterone acetate/ Annovera™ TherapeuticsMD Inc Pregnancy prevention August 2018 ethinyl estradiol elagolix Orilissa® AbbVie Pain with endometriosis July 2018 tafenoquine Krintafel® GSK Radical cure of P. vivax malaria July 2018 tecovirimat Tpoxx™ Siga Technologies Smallpox July 2018 glycopyrronium tosylate Qbrexa™ Dermina Excessive sweating July 2018 plazomicin Zemdri™ Achaogen Complicated urinary tract infections July 2018 moxidectin Moxidectin™ Medicines River blindness June 2018 Development for Global Health erenumab-aooe Aimovig® Amgen/Novartis Prevention of migraine May 2018 sodium zirconium cyclosilicate Lokelma™ AstraZeneca Hyperkalemia May 2018 lofexidine Lucemyra™ US WorldMeds Mitigation of opioid withdrawal symptoms May 2018 coagulation factor Xa Andexxa® Portola Factor Xa reversal agent May 2018 (recombinant), inactivated-zhza bictegravir/emtricitabine/ Biktarvy™ Gilead HIV February 2018 tenofovir alafenamide *Date indicates FDA approval date only. The product launch and marketing dates are determined by the approved product’s manufacturer. continued Drug Pipeline Monthly Update: December 2018 Page 4 Other new product approvals in the past twelve months Generic name Brand name Manufacturer Indication(s) Date approved* itraconazole capsule Tolsura™ Mayne Pharma Fungal infections December 2018 lamivudine/tenofovir disoproxil Temixys™ Celltrion HIV November 2018 fumarate sufentanil Dsuvia™ AcelRx Pain November 2018 Pharmaceuticals clobazam oral soluble film (OSF) Sympazan™ Aquestive Lennox-Gastaut syndrome November 2018 Therapeutics levoleucovorin Khapzory™ Spectrum Rescue after high-dose methotrexate October 2018 therapy halobetasol propionate lotion Bryhali™ Bausch Health Cos Plaque psoriasis October 2018 0.01% Inc (Valeant) meloxicam orally disintegrating Qmiiz ODT™ TerSera Pain and inflammation October 2018 tables estradiol and progesterone Bijuva™ TherapeuticsMD Vasomotor symptoms due to menopause October 2018 testosterone enanthate Xyosted™ Antares Testosterone replacement therapy October 2018 latanoprost Xelpros™ Sun Pharma Open-angle glaucoma September 2018 buprenorphine/naloxone SL film Cassipa™ Teva Opioid dependence September 2018 doravirine, lamivudine and Delstrigo™ Merck HIV September 2018 tenofovir disoproxil fumarate loteprednol etabonate Inveltys™ Kala Pharmaceuticals Post-operative inflammation and pain September 2018 following ocular surgery tretinoin Altreno™ Ortho Dermatologic Acne September 2018 methylphenidate Jornay PM™ Ironshore ADHD August 2018 Pharmaceuticals cyclosporine Cequa™ Sun Pharma Dry eye disease August 2018 tafenoquine Arakoda™ 60 Degrees Prevention of malaria August 2018 Pharmaceuticals risperidone injectable Perseris™ Indivior Schizophrenia August 2018 pimavanserin, 34 mg capsule, Nuplaxid® Acadia Parkinson’s disease psychosis July 2018 10 mg tablet Pharmaceutical darunavir, cobicistat, Symtuza® Janssen HIV July 2018 emtricitabine, tenofovir alafenamide aripiprazole lauroxil Aristada Initio™ Alkermes Schizophrenia July 2018 desmopressin Nocdurna™ Ferring Nocturia July 2018 Pharmaceuticals celecoxib/amlodipine Consensi™ Kitov Pharma Osteoarthritis pain/hypertension May 2018 vaginal estradiol Imvexxy™ TherapeuticsMD Menopause symptoms May 2018 polyethylene glycol 3350, sodium Plenvu® Norgine Osmotic laxative May 2018 ascorbate, sodium sulfate, ascorbic acid, sodium chloride and potassium chloride for oral solution continued Drug Pipeline Monthly Update: December 2018 Page 5 Other new product approvals in the past 12 months (continued) Generic name Brand name Manufacturer Indication(s) Date approved* efavirenz, lamivudine, tenofovir Symfi™ Mylan HIV April 2018 disoproxil fumarate efavirenz, lamivudine,