Drug Pipeline MONTHLY UPDATE Critical updates in an ever changing environment March 2020 NEW DRUG INFORMATION ™ ● Anjeso (meloxicam IV): The U.S. Food and Drug Administration (FDA) approved Baudax Bio’s Anjeso for the treatment of moderate-to-severe pain. Anjeso has 30mg of meloxicam per mL and is health care administered as a once-daily intravenous bolus injection. Anjeso was approved based on two Phase 3 trials that evaluated postoperative pain in patients compared to placebo. Results demonstrated statistically significant reduction in the pain, based on the numeric pain rating scale (NPRS: baseline of 6.8) as the primary end point over the first 48 hours.1 Approval came after two complete response letter (CRL) denials from the FDA concerning onset and duration of the medication. Baudax Bio plans on launching Anjeso in late April or early May 2020 with a cost of $94 per treatment.2 ™ ● Twirla (ethinyl estradiol and levonorgestrel transdermal system): Agile Therapeutics’ Twirla received an FDA approval as a low dose contraceptive patch for the prevention of pregnancy. Twirla is a once weekly patch that Agile Therapeutics states should help increase patient compliance. As part of Twila’s approval, the FDA is requiring Agile Therapeutics to conduct a long-term prospective study comparing the risks for venous thromboembolism (VTE) and arterial thromboembolism (ATE) in new users of Twirla versus other combined hormonal contraceptives. The final study report for the Twirla study is scheduled to be submitted to the FDA in November 2032, with interim safety data reporting in November 2026. The FDA has requested additional post-marketing commitment from Agile Therapeutics to assess the residual drug content and strength.3 Currently, the only other transdermal patch available on the market is the generic version of Ortho Evra, Xulane®, that delivers 150mcg of a different progestin, norelgestromin, and 35mcg of ethinyl estradiol per day.4 Twirla is set to launch in fourth quarter 2020 with pricing to follow.5 ™ ● Vyepti (eptinezumab-jjmr): The FDA approved Adler BioPharmaceuticals’ Vyepti for the prevention of migraine. Vyepti is the first intravenous calcitonin gene-related peptide (CGRP) (compared to available subcutaneous CGRPs) that is used as preventive migraine treatment, which should be administered once every three months. Vyepti’s approval is based off two clinical trials, PROMISE-1 and PROMISE-2, which measured the frequency of migraines patients had compared to baseline. The clinical trials demonstrated a treatment benefit over placebo that was observed for both doses (100mg, 300mg) of Vyepti. PROMISE-1 demonstrated that Vyepti decreased migraine days by three to four days per month compared to baseline. PROMISE-2 demonstrated Vyetpti reduced migraine days by seven to eight days per month compared to baseline.6 Adler BioPharmaceuticals plans to launch Vyepti in April 2020 with wholesale acquisition cost (WAC) of $5,980 per year.7 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 2020 Page 2 ™ ● Nexletol (bempedoic acid): Esperion Therapeutics’ Nexletol has been approved by the FDA as an adjunct to diet and maximally tolerated statin therapy for the treatment of adults with heterozygous familial hypercholesterolemia or established atherosclerotic cardiovascular disease who require additional lowering of LDL-C. Nexletol is a first-in-class ATP citrate lyase inhibitor. In the past few years, there has been excitement over PCSK9 monoclonal antibodies for the treatment of cholesterol, however these agents are delivered subcutaneously and are very expensive. The FDA-approved Nexletol, based on Phase 3 study, demonstrated an average of 18% reduction of LDL-C when used with moderate or high intensity statins, compared with placebo.8 Esperion Therapeutics plan to launch Nexletol on March 30, 2020 with a wholesale acquisition cost (WAC) of $10 per day.9 ™ ● Nexlizet (bempedoic acid and ezetimibe): Esperion Therapeutics’ Nexlizet has been approved by the FDA as an adjunct to diet and maximally tolerated statin therapy for the treatment of adults with heterozygous familial hypercholesterolemia or established atherosclerotic cardiovascular disease who require additional lowering of LDL-C. Nexlizet was approved based on the Phase 3 Fixed Combination Drug Product lowering program, as well as safety data from the bempedoic acid tablet Phase 3 trial. Nexlizet lowered LDL-C by a mean of 38% compared to placebo when added on to maximally tolerated statins.10 Esperion Therapeutics plan to launch Nexlizet in July 2020 with a WAC of $10 per day. ™ ● Barhemsys (amisulpride): The FDA has approved Acacia Pharma’s Barhemsys for post-operative nausea and vomiting who are symptomatic despite having received prophylactic treatment. Barhemsys is an intravenous selective dopamine antagonist that can be used as prophylaxis or treatment as a single agent or in combination. The FDA approved Barhemsys based on four Phase 3 studies of more than 3,300 people. The studies demonstrated Barhemsys 10mg dose alone was significantly more effective at reducing post-operative nausea and vomiting compared to placebo (42% vs. 29%) and Barhemsys 5mg dose in combination with another antiemetic significantly reduced nausea and vomiting compared to placebo (58% vs 47%).11 Acacia Pharma plans to launch Barhemsys in the second half of 2020 with pricing to follow. ™ ● Nurtec ODT (rimegepant): Biohaven’s Nurtec orally disintegrating tablet (ODT) was approved by the FDA for treatment of acute migraine. Nurtec ODT is not for preventive migraine. Nurtec ODT is the only fast-dissolving formulation of the calcitonin gene-related peptide (CGRP) receptor antagonist class. Nurtec ODT, 75mg, can be taken without water and delivers pain relief within one hour, with sustained efficacy up to 48 hours.12 The FDA approved Nurtec ODT based on two Phase 3 clinical trials that demonstrated freedom from most bothersome symptoms at two hours post dose compared to placebo. Eighty-six percent of patients treated with Nurtec ODT did not require rescue medications within 24 hours post dose. In January 2020 the Institute for Clinical and Economic Review (ICER) evaluated CGRP receptor antagonist class and found Eli Lilly’s Reyvow® (lasmiditan), Biohaven’s Nurtec® (rimegepant) and Allergan’s Ubrelvy® (ubrogepant) all perform better than placebo, but evidence is not adequate to distinguish among them. For acute migraines, ICER states generic triptans would be the most effective and cost effective.13 Biohaven launched Nurtec ODT in March 2020, available in blister packs of eight tablets, with a WAC of $4,200-$4,600 annually.14 Drug Pipeline Monthly Update: March 2020 Page 3 ™ ● Durysta (bimatoprost sustained release implant): Allergan’s Durysta has been approved by the FDA for reduction of intraocular pressure (IOP) in patients with primary open-angle glaucoma or ocular hypertension. Durysta is a biodegradable intracameral implant that is limited to a single implant per eye and should not be re-administered to an eye previously treated with Durysta due to possible corneal endothelial cell loss. The FDA approved Durysta based on two Phase 3 studies of Durysta verses twice daily topical timolol 0.5% drops. Durysta reduced IOP by approximately 30% from baseline over the 12-week primary efficacy period (approximately 5-8mmHg in patients with a mean baseline IOP of 24.5mmHg) compared to competitior.15 Bimatoprost is available generically as an ophthalmic solution for the same indication as Allergan’s Durysta™ (bimatoprost sustained release implant). Launch and pricing pending. GENERIC DRUG INFORMATION ® ● Camptosar inj (irinotecan inj)+: Areva Pharmaceuticals has launched its generic version of Pfizer’s Camptosar injection for treatment of colorectal cancer. There are no longer any regulatory exclusivities. Camptosar generated $10 million in U.S. annual sales in 2018. ® ● Metastron inj (strontium-89 chloride inj)+: Biomed has launched its generic version of GE Health Care’s Metastron injection for treatment of bone pain in patients with skeletal metastases. Annual sales for Metastron are unknown. ® ● Phenobarbital inj (phenobarbital inj): Cameron Pharmaceuticals launched its version of Hikma’s Phenobarbital injection used as an anticonvulsant. Phenobarbital injection annual sales are unknown. ® ● Vimovo (naproxen/esomeprazole DR): Dr Reddy’s launched its version of Horizon Therapeutics’ Vimovo for treatment of osteoarthritis, rheumatoid arthritis and ankylosing spondylitis. Multiple manufacturers are set to launch in 2020. Vimovo generated $578 million in U.S. annual sales in 2018. ® ● Dymista (azelastine/fluticasone nasal spray): Apotex launched its version of Mylan’s Dymista for treatment of seasonal allergic rhinitis. Apotex is eligible for 180-day exclusivity. Multiple manufacturers are set to launch their generic versions of Dymista in August 2020. Dymista generated $141 million in U.S. annual sales in 2018. ® ● Geodon (ziprasidone inj): Gland Pharma launched its version of Pfizer’s Geodon injection for the treatment of schizophrenia. There are no longer any regulatory exclusivities on Geodon. Geodon injection generated