Drug Pipeline Monthly Update Critical updates in an ever changing environment March 2018 New drug information ● Apadaz™ (benzhydrocodone/acetaminophen): KemPharm received Food and Drug Administration (FDA) approval for Apadaz for the short-term (no more than 14 days) management of acute pain severe enough to require an opioid analgesic and for which alternative treatments are inadequate. Benzhydrocodone is a prodrug of the opioid agonist hydrocodone. KemPharm originally applied for an abuse-deterrent indication, the final approved product labelling does not include abuse-deterrent labeling as the results did not demonstrate abuse-deterrence by current measurement standards. Apadaz was scheduled as a CII, a drug that has the potential to be abused. ● ZTlido™ (lidocaine topical system): Sorrento Therapeutics received FDA approval for ZTlido for the relief of pain associated with post-herpetic neuralgia also known as post-shingles pain. Up to three patches may be applied to the skin to cover the most painful area for up to 12 hours in a 24-hour period. Compared with one Lidoderm® (lidocaine patch 5%, 700 mg), one ZTlido (1.8%, 36mg) provides equivalent lidocaine exposure due to a non-aqueous adhesive material.1 ● Symfi Lo™ (efavirenz [EFV], lamivudine [3TC], and tenofovir disoproxil fumarate [TDF]): The FDA approved Mylan’s Symfi Lo as a complete regimen for the treatment of human immunodeficiency virus type 1 (HIV-1) infection. Symfi Lo contains 400 mg of EFV, 300 mg of 3TC, and 300 mg of TDF. Symfi Lo provides a complete regimen with a lower dose of efavirenz than Gilead’s Atripla® (600 mg EFV, 200 mg emtricitabine, and 300 mg TDF). Launch is expected in March or April 2018.2 Mylan plans to discount Symfi Lo’s wholesale acquisition cost (WAC) significantly from the WAC of other single tablet regimens available in the United States.3 ● Cimduo™ (lamivudine/TDF): Mylan also received approval for Cimduo, a 2-drug combination of 3TC and TDF to be used in combination with other antiretroviral agents for the treatment of HIV-1 infection. CimDuo is expected to launch in the second quarter of 2018.2 Mylan will set Cimduo’s WAC at a significant discount compared to other tenofovir-based double combination products available in the US.3 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: March 2018 Page 2 Generic drug information ● Namenda XR® (memantine ER): Mylan, Par Pharma, Amneal Pharmaceuticals, and Lupin Pharmaceuticals launched their generic versions of Allergan’s Namenda XR for the treatment of Alzheimer’s disease. According to IMS data, Namenda XR had $929 million in annual sales in the U.S. ● Solodyn® (minocycline ER): Both Teva and Impax Generics launched their generic versions of Valeant’s Solodyn in the strengths of 65 mg and 115 mg for the treatment of acne. Generic versions of the 55 mg, 80 mg, and 105 mg are expected in February 2019. According to IMS data, Solodyn had $148 million in annual sales in the U.S. ● Ritalin LA® (methylphenidate LA): Sandoz and Mayne Pharma launched their generic versions of Novartis’ Ritalin LA 10 mg capsule. This is the first generic for Ritalin LA 10 mg, generic versions of other strengths have already been launched. ● Gabitril® (tiagabine 12 mg, 16 mg): Amneal launched their generic version for Cephalon’s Gabitril tablets for the adjunctive therapy in adults and children 12 years and older in the treatment of partial seizures. Generic versions of other strengths have already been launched. No patents or exclusivities remain. Drug Pipeline Monthly Update: March 2018 Page 3 New molecular entity approvals in the past twelve months Generic name Brand name Manufacturer Indication(s) Date approved* benzhydrocodone/ Apadaz™ KemPharm Pain March 2018 acetaminophen bictegravir/ Biktarvy™ Gilead HIV February 2018 emtricitabine/ tenofovir alafenamide ertugliflozin Steglatro™ Merck/Pfizer Diabetes December 2017 ozenoxacin Xepi™ Medimetriks Impetigo December 2017 netarsudil Rhopressa® Aerie Glaucoma or ocular hypertension December 2017 Pharmaceuticals semaglutide Ozempic™ Novo Nordisk Diabetes December 2017 letermovir Prevymis™ Merck Prophylaxis of CMV infection and disease November 2017 secnidazole Solosec™ Symbiomix Bacterial vaginosis October 2017 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 *Date indicates FDA approval date only. The product launch and marketing dates are determined by the approved product’s manufacturer. Other new product approvals in the past twelve months Generic name Brand name Manufacturer Indication(s) Date approved* efavirenz, lamivudine, tenofovir Symfi Lo™ Mylan HIV March 2018 disoproxil fumarate lamivudine, tenofovir disoproxil Cimduo™ Mylan HIV March 2018 fumarate lidocaine topical system 1.8% ZTlido™ Sorrento Pain associated with post-herpetic March 2018 Therapeutics neuralgia (PHN) amantadine extended-release Osmolex ER™ Osmotica Parkinson’s disease and drug-induced February 2018 Pharmaceutical extrapyramidal symptoms ertugliflozin/metformin Segluromet™ Merck/Pfizer Diabetes December 2017 ertugliflozin/sitagliptin Steglujan™ Merck/Pfizer Diabetes December 2017 mometasone furoate Sinuva™ Intersect ENT, Inc Recurrent nasal polyps December 2017 glycopyrrolate Lonhala™ Sunovion COPD December 2017 Magnair™ Pharmaceuticals dolutegravir/rilpivirine Juluca™ Viiv Healthcare HIV-1 infection December 2017 sodium hyaluronate TriVisc™ OrthogenRx, Inc Osteoarthritis November 2017 aprepitant Cinvanti™ Heron Therapeutics Chemotherapy-induced nausea and November 2017 vomiting continued Drug Pipeline Monthly Update: March 2018 Page 4 Other new product approvals in the past 12 months (continued) Generic name Brand name Manufacturer Indication(s) Date approved* aripiprazole with sensor Abilify® MyCite™ Otsuka Drug-device combo for schizophrenia, November 2017 bipolar disorder and major depression latanoprostene bunod Vyzulta® Valeant Glaucoma or ocular hypertension November 2017 Pharmaceuticals pregabalin extended-release Lyrica® CR Pfizer Neuropathic pain October 2017 rolapitant Varubi™ Tesara/Opko Health Chemotherapy-induced nausea and October 2017 vomiting exenatide extended-release Bydureon® BCise™ AstraZeneca Diabetes October 2017 insulin aspart FIAsp™ Novo Nordisk Diabetes October 2017 fluticasone propionate nasal Xhance™ Optinose US, Inc Nasal polyps October 2017 spray fluticasone furoate, Trelegy™ Ellipta® GSK/Innoviva COPD September 2017 umeclidinium, vilanterol amphetamine extended-release Adzenys™ ER Neos Therapeutics ADHD September 2017 suspension spironolactone suspension CaroSpir™ CMP Pharma Cardiovascular August 2017 insulin lispro Admelog® Sanofi Diabetes September 2017 (full approval December 2017) lesinurad/allopurinol Duzallo™ Ironwood Uncontrolled gout August 2017 Pharmaceuticals pitavastatin sodium Nikita™ Lupin High cholesterol August 2017 beclomethasone dipropionate Qvar® RediHaler™ Teva Asthma August 2017 insulin glargine Lusduna® Nexvue™ Merck Diabetes August 2017 methylphenidate Cotempla™ XR-ODT Neos Therapeutics ADHD July 2017 extended-release orally disintegrating tablets mixed salts of a single-entity Mydayis™ Shire ADHD July 2017 amphetamine products pitavastatin Zypitamag™ 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 with abuse-deterrent properties April 2017 Daiichi Sankyo *Date indicates FDA approval date only. The product launch and marketing dates are determined by the approved product’s manufacturer. Drug Pipeline Monthly Update: March 2018 Page 5 Pipeline watch Anticipated FDA Generic Name Brand Name Manufacturer Indication(s) Decision Date acetaminophen/ibuprofen Maxigesic® AFT Pharmaceuticals Pain December 2017 testosterone undecanoate Jatenzo™ Clarus Therapeutics Testosterone replacement December 2017 promethazine/hydrocodone/ Hydexor™ Charleston Labs Pain and opioid-induced nausea and April 2018 acetaminophen vomiting levodopa inhalation powder Inbrija™ Acorda Therapeutics Off symptoms of Parkinson’s disease April 2018 elagolix N/A Abbvie Inc./ Pain associated with endometriosis May 2018 Neurocrine Biosciences andexanet alfa AndexXa™ Portola Anticoagulant reversal agent May 2018 testosterone undecanoate Tlando™ Testosterone Lipocine May 2018 replacement polyethylene glycol and Plenvu™ Salix and Norgine Bowel cleansing May 2018 ascorbate botulinum toxin type A Evosyal™ Evolus/Daewoong Frown lines May 2018 vaginal estradiol Yuvvexy™ TherapeuticsMD Menopause May 2018 celecoxib/amlodipine Consensi™ Kitov Pharma Osteoarthritis pain/hypertension May 2018 lofexidine N/A US WorldMeds Opioid use disorder May 2018 moxidectin N/A Medicines River blindness June 2018 Development for Global Health plazomicin N/A Achaogen Bacterial infection June 2018 tafenoquine N/A 60 Degrees Prevention