Highlights from the Academy of Managed Care Pharmacy

Highlights from the Academy of Managed Care Pharmacy Managed Care & Specialty Pharmacy Annual Meeting 2019 March 25–28, 2019 San Diego, CA RESULTS WITH JUST LIGHTEN THE BURDEN OF A FEW DOSES1,2 FREQUENT DOSING1,3

With just 2 doses at Week 12, 64% ILUMYA™ is dosed at Weeks 0, 4, and 61% achieved PASI 75 (reSURFACE 1 and every 12 weeks thereafter and reSURFACE 2, respectively) – vs placebo: 6% and 6% (reSURFACE 1 1 and reSURFACE 2, respectively) DURABLE SAFETY PROFILE 64 With just 3 doses at Week 28, 74% WEEKS Through Week 64, the frequency of and 70% achieved PASI 75 (reSURFACE 1 adverse reactions was similar to that and reSURFACE 2, respectively)* during the placebo-controlled period of the trial, and no new adverse reactions were identifi ed VISIT ILUMYAPRO.COM 1 RESULTS THROUGH WEEK 64 IMPORTANT SAFETY INFORMATION (cont’d) Based on PASI 75 responders at Week 28 (reSURFACE 1) * These endpoints were considered “other” Infections secondary endpoints in reSURFACE 1 and 2. ILUMYA™ may increase the risk of infection. Treatment with ILUMYA™ should not be initiated in 84% maintained PASI 75* All results based on the recommended 100 mg patients with a clinically important active infection until the infection resolves or is adequately treated. – vs 22% placebo dose of ILUMYA™. Consider the risks and benefi ts of treatment prior to prescribing ILUMYA™ in patients with a chronic infection or a PASI=Psoriasis Area and Severity Index; history of recurrent infection. Instruct patients receiving ILUMYA™ to seek medical help if signs or symptoms of clinically PGA=Physician Global Assessment. important chronic or acute infection occur. If a patient develops a clinically important or serious infection, or is not responding to standard therapy, closely monitor and consider discontinuation of ILUMYA™ until the infection resolves. Pretreatment Evaluation for Tuberculosis reSURFACE 1 and 2 were Phase 3, double-blind, placebo-controlled trials of ILUMYA™ given at Weeks 0, 4, and every 12 weeks thereafter. Patients in reSURFACE 1 (N=463) and reSURFACE 2 (N=463) with moderate-to-severe plaque psoriasis who were candidates for phototherapy or systemic therapy were Evaluate patients for tuberculosis (TB) infection prior to initiating treatment with ILUMYA™. Do not administer ILUMYA™ randomized to ILUMYA™ 100 mg or placebo. At Week 28, patients in reSURFACE 1 initially randomized to ILUMYA™ who achieved at least PASI 75 were to patients with active TB infection. Initiate treatment of latent TB prior to administering ILUMYA™. Consider anti-TB re-randomized to either continue initial treatment or to receive placebo up to 64 weeks. The co-primary endpoints of both trials were: 1) the proportion of therapy prior to initiation of ILUMYA™ in patients with a past history of latent or active TB in whom an adequate subjects who achieved at least PASI 75 and 2) the proportion of subjects with a PGA 0 or 1 and at least a 2 point improvement, both at Week 12. Other evaluated outcomes included PASI 90/100 at Week 12 and PASI 75 at Week 28. reSURFACE 1 also measured maintenance of e¨ cacy in responders up to Week 64.1,2 course of treatment cannot be confi rmed. Patients receiving ILUMYA™ should be monitored closely for signs and symptoms of active TB during and after treatment. INDICATION ILUMYA™ (tildrakizumab-asmn) is indicated for the treatment of adults with moderate-to-severe Immunizations Prior to initiating therapy with ILUMYA™, consider completion of all age-appropriate immunizations according to plaque psoriasis who are candidates for systemic therapy or phototherapy. current immunization guidelines. Patients treated with ILUMYA™ should not receive live vaccines. IMPORTANT SAFETY INFORMATION Adverse Reactions CONTRAINDICATIONS The most common (≥1%) adverse reactions associated with ILUMYA™ treatment that were more frequent than ILUMYA™ is contraindicated in patients with a previous serious hypersensitivity reaction to tildrakizumab in the placebo group are upper respiratory infections, injection-site reactions, and diarrhea. or to any of the excipients. Please see brief summary of Full Prescribing Information on next page or visit ILUMYApro.com WARNINGS AND PRECAUTIONS Hypersensitivity References: 1. ILUMYA™ [package insert]. Princeton, NJ: Sun Pharmaceuticals, Inc. 2. Data on File. Sun Pharmaceutical Industries, Inc. 3. Rigopoulos D, Ioannides D, The ILUMYA™ trademark is the property of Sun Pharma Global FZE. Cases of angioedema and urticaria occurred in ILUMYA™-treated subjects in clinical trials. Chaidemenos G, et al. Patient preference study for di erent characteristics of systemic © 2018 Sun Dermatology, a division of Sun Pharmaceutical If a serious allergic reaction occurs, discontinue ILUMYA™ immediately and initiate appropriate therapy. psoriasis treatments (Protimisis). Dermatol Ther. 2018;31(3):e12592. Industries, Inc. All rights reserved. PM-US-ILY-0203 12/2018

TILD18CDPR7874_Branded_Jrnl_Ad_Spread_r11.indd 1 1/9/19 4:07 PM RESULTS WITH JUST LIGHTEN THE BURDEN OF A FEW DOSES1,2 FREQUENT DOSING1,3

TILD18CDPR7874_Branded_Jrnl_Ad_Spread_r11.indd 1 1/9/19 4:07 PM Brief Summary of Prescribing Information for ILUMYA™ (tildrakizumab-asmn) Safety Through Week 52/64 ILUMYA™ (tildrakizumab-asmn) injection, for subcutaneous use Through Week 52 (Trials 1 and 3) and Week 64 (Trial 2), no new adverse reactions were See package insert for full Prescribing Information identified with ILUMYA use and the frequency of the adverse reactions was similar to that observed during the placebo-controlled period. INDICATIONS AND USAGE ILUMYA™ is indicated for the treatment of adults with moderate- to-severe plaque psoriasis who are candidates for systemic therapy or phototherapy. Immunogenicity As with all therapeutic proteins there is the potential for immunogenicity. The detection CONTRAINDICATIONS of antibody formation is highly dependent on the sensitivity and specificity of the assay. ILUMYA is contraindicated in patients with a previous serious hypersensitivity reaction to Additionally, the observed incidence of antibody (including neutralizing antibody) tildrakizumab or to any of the excipients [see Warnings and Precautions]. positivity in an assay may be influenced by several factors including assay methodology, WARNINGS AND PRECAUTIONS sample handling, timing of sample collection, concomitant medications, and underlying Hypersensitivity: Cases of angioedema and urticaria occurred in ILUMYA treated disease. For these reasons, comparison of incidence of antibodies to tildrakizumab in the subjects in clinical trials. If a serious hypersensitivity reaction occurs, discontinue ILUMYA studies described below with the incidences of antibodies in other studies or to other immediately and initiate appropriate therapy [see Adverse Reactions]. products may be misleading. Infections: ILUMYA may increase the risk of infection. Although infections were slightly Up to Week 64, approximately 6.5% of subjects treated with ILUMYA 100 mg developed more common in the ILUMYA group (23%), the difference in frequency of infections antibodies to tildrakizumab. Of the subjects who developed antibodies to tildrakizumab, between the ILUMYA group and the placebo group was less than 1% during the placebo- approximately 40% (2.5% of all subjects receiving ILUMYA) had antibodies that were controlled period. However, subjects with active infections or a history of recurrent classified as neutralizing. Development of neutralizing antibodies to tildrakizumab was infections were not included in clinical trials. Upper respiratory infections occurred more associated with lower serum tildrakizumab concentrations and reduced efficacy. frequently in the ILUMYA group than in the placebo group [see Adverse Reactions]. DRUG INTERACTIONS The rates of serious infections for the ILUMYA group and the placebo group were ≤0.3%. Live Vaccinations Treatment with ILUMYA should not be initiated in patients with any clinically important Avoid use of live vaccines in patients treated with ILUMYA [see Warnings and Precautions]. active infection until the infection resolves or is adequately treated. USE IN SPECIFIC POPULATIONS In patients with a chronic infection or a history of recurrent infection, consider the risks Pregnancy: Risk Summary and benefits prior to prescribing ILUMYA. Instruct patients to seek medical help if signs or Limited available data with ILUMYA use in pregnant women are insufficient to inform a symptoms of clinically important chronic or acute infection occur. If a patient develops a drug associated risk of adverse developmental outcomes. Human IgG is known to cross clinically important or serious infection or is not responding to standard therapy, monitor the placental barrier; therefore, ILUMYA may be transferred from the mother to the fetus. the patient closely and consider discontinuation of ILUMYA until the infection resolves [see An embryofetal developmental study conducted with tildrakizumab in pregnant monkeys Adverse Reactions]. revealed no treatment-related effects to the developing fetus when tildrakizumab was Pretreatment Evaluation for Tuberculosis: Evaluate patients for tuberculosis (TB) administered subcutaneously during organogenesis to near parturition at doses up to 159 infection prior to initiating treatment with ILUMYA. Initiate treatment of latent TB prior to times the maximum recommended human dose (MRHD). When dosing was continued administering ILUMYA. In clinical trials, of 55 subjects with latent TB who were concurrently until parturition, a small increase in neonatal death was observed at 59 times the MRHD treated with ILUMYA and appropriate TB prophylaxis, no subjects developed active [see Data]. The clinical significance of this nonclinical finding is unknown. TB (during the mean follow-up of 56.5 weeks). One other subject developed TB while All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. receiving ILUMYA. Monitor patients for signs and symptoms of active TB during and after The background risk of major birth defects and miscarriage for the indicated population ILUMYA treatment. Consider anti-TB therapy prior to initiation of ILUMYA in patients with is unknown. In the U.S. general population, the estimated background risk of major a past history of latent or active TB in whom an adequate course of treatment cannot be birth defects and miscarriage in clinically recognized pregnancies is 2-4% and confirmed. Do not administer ILUMYA to patients with active TB infection. 15-20%, respectively. Immunizations: Prior to initiating therapy with ILUMYA, consider completion of all age Data: Animal Data appropriate immunizations according to current immunization guidelines. Avoid the use of In an embryofetal developmental study, subcutaneous doses up to 300 mg/kg live vaccines in patients treated with ILUMYA. No data are available on the response to live tildrakizumab were administered to pregnant cynomolgus monkeys once every two weeks or inactive vaccines. during organogenesis to gestation day 118 (22 days from parturition). No maternal or ADVERSE REACTIONS embryofetal toxicities were observed at doses up to 300 mg/kg (159 times the MRHD of The following serious adverse reactions are discussed elsewhere in the labeling: 100 mg, based on AUC comparison). Tildrakizumab crossed the placenta in monkeys. Hypersensitivity Reactions [see Warnings and Precautions] In a pre- and postnatal developmental study, subcutaneous doses up to 100 mg/kg Infections [see Warnings and Precautions] tildrakizumab were administered to pregnant cynomolgus monkeys once every two Clinical Trial Experience weeks from gestation day 50 to parturition. Neonatal deaths occurred in the offspring Because clinical trials are conducted under widely varying conditions, adverse reaction of one control monkey, two monkeys at 10 mg/kg dose (6 times the MRHD based on rates observed in the clinical trials of a drug cannot be directly compared to rates in the AUC comparison), and four monkeys at 100 mg/kg dose (59 times the MRHD based on clinical trials of another drug and may not reflect the rates observed in practice. AUC comparison). The clinical significance of these nonclinical findings is unknown. No In clinical trials, a total of 1994 subjects with plaque psoriasis were treated with ILUMYA, tildrakizumab-related adverse effects were noted in the remaining infants from birth of which 1083 subjects were treated with ILUMYA 100 mg. Of these, 672 subjects were through 6 months of age. exposed for at least 12 months, 587 for 18 months, and 469 for 24 months. Lactation: Risk Summary Data from three placebo-controlled trials (Trials 1, 2, and 3) in 705 subjects (mean age There are no data on the presence of tildrakizumab in human milk, the effects on the 46 years, 71% males, 81% white) were pooled to evaluate the safety of ILUMYA (100 mg breastfed infant, or the effects on milk production. Human IgG is known to be present in administered subcutaneously at Weeks 0 and 4, followed by every 12 weeks [Q12W]) [see human milk. Tildrakizumab was detected in the milk of monkeys [see Data]. Clinical Studies]. The developmental and health benefits of breastfeeding should be considered along with Placebo-Controlled Period (Weeks 0-16 of Trial 1 and Weeks 0-12 of Trials 2 and 3) the mother’s clinical need for ILUMYA and any potential adverse effects on the breastfed In the placebo-controlled period of Trials 1, 2, and 3 in the 100 mg group, adverse events child from ILUMYA or from the underlying maternal condition. occurred in 48.2% of subjects in the ILUMYA group compared to 53.8% of subjects in the Pediatric Use: Safety and effectiveness of ILUMYA in pediatric patients (<18 years of age) placebo group. The rates of serious adverse events were 1.4% in the ILUMYA group and have not been established. 1.7% in the placebo group. Geriatric Use: A total of 1083 subjects were exposed to ILUMYA 100 mg during Phase 2 Table 1 summarizes the adverse reactions that occurred at a rate of at least 1% and at a and 3 trials. A total of 92 subjects were 65 years or older, and 17 subjects were 75 years higher rate in the ILUMYA group than in the placebo group. or older. Although no differences in safety or efficacy were observed between older and Table 1: Adverse Reactions Occurring in ≥1% of Subjects in the ILUMYA Group and younger subjects, the number of subjects aged 65 and over is not sufficient to determine More Frequently than in the Placebo Group in the Plaque Psoriasis Trials 1, 2, and 3 whether they respond differently from younger subjects. Adverse Reaction ILUMYA 100 mg Placebo OVERDOSAGE: In the event of overdosage, monitor the patient for any signs or symptoms (N=705) N (%) (N=355) N (%) of adverse reactions and administer appropriate symptomatic treatment immediately. PATIENT COUNSELING INFORMATION: Advise the patient and/or caregiver to read the Upper respiratory 98 (14) 41 (12) FDA-approved patient labeling (Medication Guide). infections* Instruct patients and/or caregivers to read the Medication Guide before starting ILUMYA Injection site reactions† 24 (3) 7 (2) therapy and to reread the Medication Guide each time the prescription is renewed. Advise Diarrhea 13 (2) 5 (1) patients of the potential benefits and risks of ILUMYA. Hypersensitivity * Upper respiratory infections include nasopharyngitis, upper respiratory tract infection, viral Advise patients to seek immediate medical attention if they experience any symptoms of upper respiratory tract infection, and pharyngitis. serious hypersensitivity reactions [see Warnings and Precautions]. † Injection site reactions include injection site urticaria, pruritus, pain, reaction, erythema, Infections inflammation, edema, swelling, bruising, hematoma, and hemorrhage. Instruct patients of the importance of communicating any history of infections to the During the placebo-controlled period of Trials 1, 2, and 3, adverse reactions that occurred doctor and contacting their doctor if they develop any symptoms of infection [see Warnings at rates less than 1% but greater than 0.1% in the ILUMYA group and at a higher rate than in and Precautions]. the placebo group included dizziness and pain in extremity. Specific Adverse Reactions Hypersensitivity Reactions Cases of angioedema and urticaria occurred in ILUMYA-treated subjects in clinical trials [see Warnings and Precautions]. Infections Manufactured by: Sun Pharma Global FZE, Inc. Infections were slightly more common in the ILUMYA group. The difference in frequency Sharjah, U.A.E. U.S. License No. 2092 of infections between the ILUMYA group (23%) and the placebo group was less than 1% Distributed by: Sun Pharmaceutical Industries, Inc., Cranbury, NJ 08512 during the placebo-controlled period. The most common (≥1%) infections were upper © 2018 Sun Pharma Global FZE. All rights reserved. respiratory infections. The rates of severe infections for the ILUMYA group and the placebo PLR-00015 group were ≤0.3%. RX ONLY

TILD18CDPR7874_Branded_Jrnl_Ad_Spread_r11.indd 2 1/4/19 11:54 AM Brief Summary of Prescribing Information for ILUMYA™ (tildrakizumab-asmn) Safety Through Week 52/64 ILUMYA™ (tildrakizumab-asmn) injection, for subcutaneous use Through Week 52 (Trials 1 and 3) and Week 64 (Trial 2), no new adverse reactions were See package insert for full Prescribing Information identified with ILUMYA use and the frequency of the adverse reactions was similar to that Highlights from the Academy of Managed Care Pharmacy observed during the placebo-controlled period. INDICATIONS AND USAGE ILUMYA™ is indicated for the treatment of adults with moderate- to-severe plaque psoriasis who are candidates for systemic therapy or phototherapy. Immunogenicity Managed Care & Specialty Pharmacy Annual Meeting 2019 As with all therapeutic proteins there is the potential for immunogenicity. The detection CONTRAINDICATIONS of antibody formation is highly dependent on the sensitivity and specificity of the assay. ILUMYA is contraindicated in patients with a previous serious hypersensitivity reaction to Additionally, the observed incidence of antibody (including neutralizing antibody) March 25–28, 2019 | San Diego, CA tildrakizumab or to any of the excipients [see Warnings and Precautions]. positivity in an assay may be influenced by several factors including assay methodology, WARNINGS AND PRECAUTIONS sample handling, timing of sample collection, concomitant medications, and underlying Hypersensitivity: Cases of angioedema and urticaria occurred in ILUMYA treated disease. For these reasons, comparison of incidence of antibodies to tildrakizumab in the subjects in clinical trials. If a serious hypersensitivity reaction occurs, discontinue ILUMYA studies described below with the incidences of antibodies in other studies or to other immediately and initiate appropriate therapy [see Adverse Reactions]. products may be misleading. Infections: ILUMYA may increase the risk of infection. Although infections were slightly Up to Week 64, approximately 6.5% of subjects treated with ILUMYA 100 mg developed more common in the ILUMYA group (23%), the difference in frequency of infections antibodies to tildrakizumab. Of the subjects who developed antibodies to tildrakizumab, between the ILUMYA group and the placebo group was less than 1% during the placebo- approximately 40% (2.5% of all subjects receiving ILUMYA) had antibodies that were controlled period. However, subjects with active infections or a history of recurrent classified as neutralizing. Development of neutralizing antibodies to tildrakizumab was infections were not included in clinical trials. Upper respiratory infections occurred more associated with lower serum tildrakizumab concentrations and reduced efficacy. frequently in the ILUMYA group than in the placebo group [see Adverse Reactions]. DRUG INTERACTIONS The rates of serious infections for the ILUMYA group and the placebo group were ≤0.3%. Live Vaccinations Table of Contents Treatment with ILUMYA should not be initiated in patients with any clinically important Avoid use of live vaccines in patients treated with ILUMYA [see Warnings and Precautions]. active infection until the infection resolves or is adequately treated. USE IN SPECIFIC POPULATIONS In patients with a chronic infection or a history of recurrent infection, consider the risks Pregnancy: Risk Summary Regulatory Guidance on Biosimilar Development, Plus a Look at the Biosimilar Pipeline and benefits prior to prescribing ILUMYA. Instruct patients to seek medical help if signs or Limited available data with ILUMYA use in pregnant women are insufficient to inform a symptoms of clinically important chronic or acute infection occur. If a patient develops a drug associated risk of adverse developmental outcomes. Human IgG is known to cross 4 clinically important or serious infection or is not responding to standard therapy, monitor the placental barrier; therefore, ILUMYA may be transferred from the mother to the fetus. the patient closely and consider discontinuation of ILUMYA until the infection resolves [see An embryofetal developmental study conducted with tildrakizumab in pregnant monkeys Adverse Reactions]. revealed no treatment-related effects to the developing fetus when tildrakizumab was Pretreatment Evaluation for Tuberculosis: Evaluate patients for tuberculosis (TB) administered subcutaneously during organogenesis to near parturition at doses up to 159 How to Address the Drug Coupon Challenge infection prior to initiating treatment with ILUMYA. Initiate treatment of latent TB prior to times the maximum recommended human dose (MRHD). When dosing was continued administering ILUMYA. In clinical trials, of 55 subjects with latent TB who were concurrently until parturition, a small increase in neonatal death was observed at 59 times the MRHD 6 treated with ILUMYA and appropriate TB prophylaxis, no subjects developed active [see Data]. The clinical significance of this nonclinical finding is unknown. TB (during the mean follow-up of 56.5 weeks). One other subject developed TB while All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. receiving ILUMYA. Monitor patients for signs and symptoms of active TB during and after The background risk of major birth defects and miscarriage for the indicated population Session Puts a Spotlight on Health Care Disruptors and Innovators ILUMYA treatment. Consider anti-TB therapy prior to initiation of ILUMYA in patients with is unknown. In the U.S. general population, the estimated background risk of major a past history of latent or active TB in whom an adequate course of treatment cannot be birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 8 confirmed. Do not administer ILUMYA to patients with active TB infection. 15-20%, respectively. Immunizations: Prior to initiating therapy with ILUMYA, consider completion of all age Data: Animal Data appropriate immunizations according to current immunization guidelines. Avoid the use of In an embryofetal developmental study, subcutaneous doses up to 300 mg/kg On the Horizon: The Specialty Pharmacy Pipeline live vaccines in patients treated with ILUMYA. No data are available on the response to live tildrakizumab were administered to pregnant cynomolgus monkeys once every two weeks or inactive vaccines. during organogenesis to gestation day 118 (22 days from parturition). No maternal or 9 ADVERSE REACTIONS embryofetal toxicities were observed at doses up to 300 mg/kg (159 times the MRHD of The following serious adverse reactions are discussed elsewhere in the labeling: 100 mg, based on AUC comparison). Tildrakizumab crossed the placenta in monkeys. Hypersensitivity Reactions [see Warnings and Precautions] In a pre- and postnatal developmental study, subcutaneous doses up to 100 mg/kg Infections [see Warnings and Precautions] tildrakizumab were administered to pregnant cynomolgus monkeys once every two Best Practices for Navigating Preapproval Information Exchange Clinical Trial Experience weeks from gestation day 50 to parturition. Neonatal deaths occurred in the offspring 10 Because clinical trials are conducted under widely varying conditions, adverse reaction of one control monkey, two monkeys at 10 mg/kg dose (6 times the MRHD based on rates observed in the clinical trials of a drug cannot be directly compared to rates in the AUC comparison), and four monkeys at 100 mg/kg dose (59 times the MRHD based on clinical trials of another drug and may not reflect the rates observed in practice. AUC comparison). The clinical significance of these nonclinical findings is unknown. No In clinical trials, a total of 1994 subjects with plaque psoriasis were treated with ILUMYA, tildrakizumab-related adverse effects were noted in the remaining infants from birth How to Manage Generics When They Become Too Costly of which 1083 subjects were treated with ILUMYA 100 mg. Of these, 672 subjects were through 6 months of age. exposed for at least 12 months, 587 for 18 months, and 469 for 24 months. Lactation: Risk Summary 11 Data from three placebo-controlled trials (Trials 1, 2, and 3) in 705 subjects (mean age There are no data on the presence of tildrakizumab in human milk, the effects on the 46 years, 71% males, 81% white) were pooled to evaluate the safety of ILUMYA (100 mg breastfed infant, or the effects on milk production. Human IgG is known to be present in administered subcutaneously at Weeks 0 and 4, followed by every 12 weeks [Q12W]) [see human milk. Tildrakizumab was detected in the milk of monkeys [see Data]. Specialty Drug Growth Continues: A Look at the Pipeline Clinical Studies]. The developmental and health benefits of breastfeeding should be considered along with Placebo-Controlled Period (Weeks 0-16 of Trial 1 and Weeks 0-12 of Trials 2 and 3) the mother’s clinical need for ILUMYA and any potential adverse effects on the breastfed 12 In the placebo-controlled period of Trials 1, 2, and 3 in the 100 mg group, adverse events child from ILUMYA or from the underlying maternal condition. occurred in 48.2% of subjects in the ILUMYA group compared to 53.8% of subjects in the Pediatric Use: Safety and effectiveness of ILUMYA in pediatric patients (<18 years of age) placebo group. The rates of serious adverse events were 1.4% in the ILUMYA group and have not been established. 1.7% in the placebo group. Real-Time Benefit Checks May Improve Medication Adherence, Reduce Patient Costs Geriatric Use: A total of 1083 subjects were exposed to ILUMYA 100 mg during Phase 2 Table 1 summarizes the adverse reactions that occurred at a rate of at least 1% and at a and 3 trials. A total of 92 subjects were 65 years or older, and 17 subjects were 75 years 14 higher rate in the ILUMYA group than in the placebo group. or older. Although no differences in safety or efficacy were observed between older and Table 1: Adverse Reactions Occurring in ≥1% of Subjects in the ILUMYA Group and younger subjects, the number of subjects aged 65 and over is not sufficient to determine More Frequently than in the Placebo Group in the Plaque Psoriasis Trials 1, 2, and 3 whether they respond differently from younger subjects. posters Adverse Reaction ILUMYA 100 mg Placebo OVERDOSAGE: In the event of overdosage, monitor the patient for any signs or symptoms (N=705) N (%) (N=355) N (%) of adverse reactions and administer appropriate symptomatic treatment immediately. PATIENT COUNSELING INFORMATION: Advise the patient and/or caregiver to read the Upper respiratory 98 (14) 41 (12) FDA-approved patient labeling (Medication Guide). Nonadherence, Switching Still a Study Finds Tildrakinzumab Is Safe in infections* Instruct patients and/or caregivers to read the Medication Guide before starting ILUMYA Problem When Treating Psoriasis 5 Patients With Metabolic Syndrome 8 Injection site reactions† 24 (3) 7 (2) therapy and to reread the Medication Guide each time the prescription is renewed. Advise Diarrhea 13 (2) 5 (1) patients of the potential benefits and risks of ILUMYA. Hypersensitivity Early PASI Response May Predict Longer- Study Finds Tildrakizumab May * Upper respiratory infections include nasopharyngitis, upper respiratory tract infection, viral Advise patients to seek immediate medical attention if they experience any symptoms of upper respiratory tract infection, and pharyngitis. serious hypersensitivity reactions [see Warnings and Precautions]. Term Outcomes for Tildrakizumab Decrease Cardiometabolic Symptoms † Injection site reactions include injection site urticaria, pruritus, pain, reaction, erythema, Infections inflammation, edema, swelling, bruising, hematoma, and hemorrhage. Instruct patients of the importance of communicating any history of infections to the in Patients With Psoriasis 7 in Patients With Psoriasis 13 During the placebo-controlled period of Trials 1, 2, and 3, adverse reactions that occurred doctor and contacting their doctor if they develop any symptoms of infection [see Warnings at rates less than 1% but greater than 0.1% in the ILUMYA group and at a higher rate than in and Precautions]. the placebo group included dizziness and pain in extremity. Specific Adverse Reactions Hypersensitivity Reactions PUBLISHER Gene Conselyea Cases of angioedema and urticaria occurred in ILUMYA-treated subjects in clinical trials [see Warnings and Precautions]. EDITOR Kerri Fitzgerald EDITORIAL SUPPORT Neal Learner Infections Manufactured by: Sun Pharma Global FZE, Inc. Infections were slightly more common in the ILUMYA group. The difference in frequency Sharjah, U.A.E. U.S. License No. 2092 ART DIRECTOR Ari Mihos of infections between the ILUMYA group (23%) and the placebo group was less than 1% Distributed by: Sun Pharmaceutical Industries, Inc., Cranbury, NJ 08512 630 Madison Avenue GRAPHIC DESIGNER Natalie Blodgett during the placebo-controlled period. The most common (≥1%) infections were upper © 2018 Sun Pharma Global FZE. All rights reserved. 2nd Floor PROJECT MANAGER Christopher Wittholt respiratory infections. The rates of severe infections for the ILUMYA group and the placebo PLR-00015 Manalapan, NJ 07726 ACCOUNT MANAGER Maria Sercia group were ≤0.3%. RX ONLY

TILD18CDPR7874_Branded_Jrnl_Ad_Spread_r11.indd 2 1/4/19 11:54 AM AMCP 2019 Highlights

Regulatory Guidance on Biosimilar Development, Barriers persist surrounding the Plus a Look at the Biosimilar uptake of biosimilars. Some of the Pipeline key areas that need improvement Eighteen biosimilars have been licensed by the Food and Drug Administration (FDA) since 2015, seven of are education for clinicians and which have launched. When submitting a biosimilar to the FDA, manufacturers must show the following: patients, improved informational • Biosimilarity to reference product materials, interchangeability • Same mechanism(s) of action (if known) requirements, health care and • Condition(s) for use (i.e., indications) were previously approved for reference product public acceptance of these agents,

• Same route, dosage form, and strength and the ‘nocebo’ effect.

• Manufacturing facility meets standards to ensure safety, purity, and potency Since last year, the FDA has released several guidance During a presentation at the AMCP Annual Meet- documents for biosimilars, including information on ing, Jennifer M. Day, PharmD, coordinator of labeling, licensing, and nonproprietary naming. And since emerging therapeutics strategy program at Kaiser 2013, 45 states and Puerto Rico have passed substitu- Permanente in Downey, California, discussed regulation laws for switching to a biosimilar. They include: tory and utilization updates for U.S. biosimilars. Former FDA Commissioner Scott Gottlieb, MD, • Must first be FDA-approved as “interchangeable” said the agency is focused on advancing policies that make the process of biosimilar development • Prescriber may prevent with “no substitutions” more efficient. The key areas of focus include: on prescription

• Improving the efficiency of the • Almost all require RPh communication to prescriber biosimilar and interchangeable product development and approval process • Many require RPh to retain records

• Maximizing scientific and regulatory clarity for • Many require patients be informed the biosimilar product development community Per the Bipartisan Budget Act of 2018, biosimi- • Supporting market competition by reducing lars can be included in coverage gap manufacturer gaming of FDA requirements or other discount program within Medicare Part D. A policy attempts to unfairly delay competition change from the Centers for Medicare & Medicaid Services resulted in lower cost-sharing for low- • Developing effective communications to income Medicare Part D beneficiaries and promotes improve understanding of biosimilars medication adherence and biosimilar utilization. among patients, clinicians, and payers Dr. Day then discussed U.S. biosimilar uptake patterns. Filgrastim-sndz launched in September 2015 and currently holds 44.3% of the filgrastim market share,

4 according to January 2019 IMS Health data. However, Presentation B3: Riding the Biosimilars Wave: in another drug class, despite having two infliximab The Latest on Utilization, Regulation and biosimilar products available, the reference product, Pipeline. AMCP Annual Meeting 2019. Remicade®, continues to hold 93% of the market share. Barriers persist surrounding the uptake of biosimilars. Some of the key areas that need improvement are education for clinicians and patients, improved informational materials, interchangeability require- How to Address the Drug ments, health care and public acceptance of these agents, and the “nocebo” effect. Other barriers include Coupon Challenge new competition from reformulated therapies, long- term contracts and rebates for reference products, The number of drugs with copay cards has soared in skinny labels and off-label use of drugs, and patent the past 10 years, from 75 drugs in 2009 to 700 drugs in litigation and settlements for reference products. 2015. These direct-to-consumer funding programs include She said that in the next 10 years, the market could see manufacturer-provided patient assistance programs (PAPs) biosimilars become available for aflibercept, alemtuzumab, and charitable PAPs. certolizumab pegol, denosumab, eculizumab, golimumab, During a presentation at the AMCP Annual Meet- natalizumab, omalizumab, onabotulinumtoxinA, pani- ing, Josh Golden, area senior vice president of Solid tumumab, ranibizumab, tocilizumab, and ustekinumab. Benefit Guidance in Atlanta, Georgia, andManual Dr. Day concluded by noting a statistic from the RAND Jayabalan, PharmD, MBA, clinical pharmacist ac- Corporation: “We estimate that biosimilars will lead to count manager of Magellan Rx Management in Can- a reduction of $54 billion in direct spending on biologic ton, Michigan, discussed different direct-to-consumer drugs from 2017 to 2026 (range $24 to $150 billion).” ■ payment and management options for payers.

POSTER

etanercept. Reinitiation rates ranged from 19% Nonadherence, Switching Still a Problem When with secukinumab to 44% with etanercept. Similar Treating Psoriasis trends were observed for the 12- and 18-month post-index periods, and outcomes were worse Many patients with moderate-to-severe psoriasis the researchers assessed: with prolonged follow-up. are treated with biologics; however, a study found • Adherence (proportion of days covered ≥0.8) “Despite many new self-administered therapies that adherence rates for these treatments were with frequent dosing [coming] to market, there low, and patients were nonpersistent with treat- • Nonpersistence (no refill within pre-defined is still [a] need for new therapies that could offer ment. The results of the study were presented at gaps for each therapy) better adherence through long-term control in an the AMCP Annual Meeting during a poster session • Discontinuation (no claim for any study medi- office setting,” the researchers concluded. titled “Biologic and Apremilast Treatment Patterns cation after a treatment gap) The study is limited by its use of a population in Moderate-to-Severe Plaque Psoriasis.” with commercial or private Medicare supplemental Researchers queried the IBM® MarketScan® • Switching (subsequent claim of the index medi- coverage, limiting the generalizability of the out- Commercial and Medicare Supplemental databases cation after a treatment gap) comes. The study also relied on information from a to identify adult patients with psoriasis who were • Reinitiation (initiation of a biologic, apremilast, or database, which could have errors. newly initiating secukinumab, ixekizumab, adali- other systemic medications that is different from mumab, ustekinumab, etanercept, or apremilast the index medication after a treatment gap) The study was sponsored by Sun between January 1, 2015, and August 31, 2018. A total of 7,773 patients were included. Over the Pharmaceutical Industries, Inc. Eligible patients had not previously received the 24-month follow-up period, adherence to treat- index agent and had no evidence of cancer or HIV ment ranged from 21% for etanercept to 33% for Feldman SR, Zhang J, Zhao Y, Martinez D, Lopez-Gonzalez over the 12-month pre-index period. Patients also secukinumab. Nonpersistence rates ranged from L, Hoit Marchlewicz E, Shrady G, Lowry S, Mendelsohn A. had continuous medical and pharmacy benefits 58% with ustekinumab to 87% with etanercept. Biologic and Apremilast Treatment Patterns in Moderate- over the 12-month pre-index and 24-month post- Discontinuation rates ranged from 38% with to-Severe Plaque Psoriasis. Abstract L5. Presented index periods. ustekinumab to 51% with adalimumab. Switching at the AMCP Managed Care & Specialty Pharmacy Annual Meeting, March 25-28; San Diego, CA. Over 12-, 18-, and 24-month follow-up periods, rates ranged from 17% with apremilast to 42% with

5 AMCP 2019 Highlights

Copay cards typically reduce copayment to a speci- sponsored debit cards may sidestep these programs. fied dollar amount that have monthly or annual caps. Patients may also be exposed to a midyear cost spike if These can be distributed in various ways (print, elec- the coupon value is exhausted (called the “coupon cliff”). tronic, debit card, and electronic systems for prescrib- Variable copay programs can also be imple- ing physicians); however, coupons are prohibited for mented to maximize the use of available direct-to- federal-funded plans, such as Medicare and Medicaid. consumer funding. Thus, copays may be scaled The speakers discussed different stakeholder per- by product or “tiered” for groups of products. spectives on these copay cards. For patients, coupons However, uptake of this solution is slow. ■ and cards can lower out-of-pocket costs, particularly at a time when cost-sharing is shifting more of the Presentation B4: The Copay Card Conundrum: Examining financial responsibility to patients. Patients often the Usage, Regulation, and Management of Direct-to- learn about coupons from the prescriber or dispens- Consumer Funding Programs. AMCP Annual Meeting 2019. ing pharmacy, or directly from the manufacturer. For manufacturers, multiple studies have shown that coupons increase treatment adherence. In addition, coupons can protect drug market share from competitors. There are also tax advantages Session Puts a Spotlight on for manufacturers, particularly for programs that are managed by charitable foundations. Health Care Disruptors and For plan sponsors, reactions to coupons vary based on the drug and class. Coupons can encourage the use of Innovators more expensive brand name products, thus increasing Despite its rising level of health care spending, the United overall costs, as coupons can increase brand drug sales States lags behind other countries in many outcomes by 60%. These coupons eliminate the financial barriers to and quality measures. Much of the U.S. health care costs off-label or inappropriate use of a product, but they can includes major administrative functions and infrastructure subvert plan design strategy and undermine formulary that bring little or no value to the system, some contend. tier decisions. Coupons can also contribute to drug cost During a presentation at the AMCP Annual Meet- inflation, as pharmaceutical companies must recover the ing, Jorge Font, MPH, senior vice president of Precision costs of these cards through wholesale price. Brand drugs for Value, LLC, in Sugar Land, Texas, and Elizabeth with coupons have been shown to have 12% to 13% annual Oyekan, PharmD, FCSHP, CPHQ, senior director of price growth, while drugs without coupons had 7% to 8% quality and population health solutions at Precision for annual price growth, according to a report from CNN. Value, LLC, in Centennial, Colorado, discussed innovative The speakers then laid out the “copay conundrum:” and disruptive companies and services that will likely Specialty drugs drive up benefit costs, leading plan change the health care landscape in the coming decade. sponsors to increase deductibles and coinsurance. Manu- Value-based care has become a key focus in health facturers then offer coupons to insured patients, and care, and while preliminary outcomes for disease-specific plan sponsors adopt management programs, so manu- conditions have shown good results, questions remain facturers offer debit cards. For plan sponsors, formulary as to the overall impact. Thus, more progress is needed, exclusions, benefit design, and utilization management particularly in areas where spending remains high. may need to be employed to manage this situation. The speakers noted that there are different arche- The speakers then discussed accumulator adjustment types for health care disruption and innovation: programs, which “back-out” the value of indirect funding for specialty drugs. Most solutions are automated within • Care delivery disruptors the adjudication platform, and these programs are frequently offered at no charge to plan sponsors. Uptake of • Technology and big data enablers this solution is increasing, as many pharmacy benefit man- agers saw a significant increase in program participation • Personalized care enhancers in 2018 and 2019. There are challenges to these programs, however, including that they are not feasible in the retail • Cost trends and access facilitators setting and self-filing is difficult. In addition, industry-

6 • Legislative and performance drivers POSTER They then gave examples for each of these categories: The CVS/Aetna merger is a care delivery disruptor that may re- Early PASI Response May Predict duce cost of care through scale and site of care and integrate Longer-Term Outcomes for data. An example of the technology and big data enablers is Tildrakizumab in Patients With health care blockchain, which helps manage clinical trials Psoriasis data and electronic medical records, while maintaining regulatory compliance. Data cannot be changed without leaving Tildrakizumab is a humanized, IgG1/ĸ monoclonal antibody that is approved for the treatment of adults with moderate-to-severe plaque a mark, and the complex coded data is highly secure. United psoriasis. In a study, researchers found that the majority of patients Healthcare, Quest, Humana, and Multiplan are participating with moderate-to-severe psoriasis treated with tildrakizumab 100 in a pilot to keep provider directories accurate, while IBM mg achieved Psoriasis Area and Severity Index (PASI) 75 at week Canada, Kalibrate, and Boehringer Ingelheim are using a 28. The results of the study were presented at the AMCP Annual blockchain app to complete medical histories in hospitals. Meeting during a poster session titled “Clinical Implications of Early The Amazon, J.P. Morgan Chase & Co., and Berkshire PASI Responses to Tildrakizumab in Patients with Moderate-to-Severe Hathaway Inc., Health Transformation Alliance is an Plaque Psoriasis.” The post-hoc analysis pooled data from two phase III trials: example of access facilitators. These corporations are reSURFACE 1 and reSURFACE 2. They included patients who were seeking to create a health system that reduces costs randomized to receive tildrakizumab 100 mg at weeks zero, four, and increases supply chain efficiency, transparency, 16, and 28. Researchers classified 575 patients based on their and consumerism by incorporating innovative technol- response: PASI <50 (n=48), PASI 50 to 74 (n=82), PASI 75 to 89 ogy, operating in a not-for-profit structure, and creating (n=137), PASI 90 to 99 (n=175), and PASI 100 (n=133). The research- consumer-focused solutions to encourage competition and ers evaluated whether early improved PASI scores could signal transparency. Use of biomarkers in cancer is an example week 28 responders. Weeks four and 16 PASI cutoff thresholds (PASI <50 or PASI ≥50) of personalized care enhancers. A more personalized were used to examine week 28 PASI responder (PASI ≥75), super approach to cancer diagnosis and care can reduce unnec- responder (PASI ≥90), and nonresponder (PASI <75) status. essary therapies, toxicities, and adverse events, as well Most patients (85%) with PASI <50 at week 16 did not achieve PASI as maximize response to and durability of treatment. ≥75 at week 28, and 58% of patients with PASI <50 at week 28 did Finally, an example of legislative and performance not achieve at least PASI 50 at week 16. Less than half of patients drivers is Medicaid’s use of social determinants of health, (41%) achieved PASI ≥50 at week four; two-thirds achieved PASI ≥90 including genetics, behavior, and social and environ- and more than 85% achieved PASI ≥75 at week 28. Among the week 28 super-responders and responders, 50% and 45%, respectively, mental factors. This includes addressing housing and achieved PASI ≥50 at week four, suggesting that PASI improvements community development, job creation, exercise, and as early as week four may predict patients’ week 28 PASI improve- education, as well as identifying public health patterns. ment status, according to the researchers. Patients achieving PASI ≥50 The Centers for Medicare & Medicaid Services is work- at week four were more likely to become responders (PASI ≥75) and ing with communities to expand their geographic reach, super-responders (PASI ≥90) by week 28. access, and success to provide more cost-effective care. The study was sponsored by Sun Pharmaceutical Industries, Inc. The speakers concluded by discussing strategies for keep- ing up with disruptors and innovators: Establish a culture Feldman SR, Merola JF, Pariser D, Zhang J, Zhao Y, Parno J, Mendelsohn A, Lowry S, and process for rapid implementation of new endeavors; Gottlieb A. Clinical Implications of Early PASI Responses to Tildrakizumab in Patients focus on quality, access, and affordability; pursue partner- with Moderate-to-Severe Plaque Psoriasis. Abstract L3. Presented at the AMCP ships; invest in data analytics and health information tech- Managed Care & Specialty Pharmacy Annual Meeting, March 25-28; San Diego, CA. nology; and focus on improving access and convenience. Necessity drives innovation, and there is currently a profound need to improve the efficiency, quality, and cost of the health care system, the speakers concluded. ■

Presentation B5: Disruptive Innovation in Health Care: The 2020 Emerging Trends, Entrants, and Drivers of Change. AMCP Annual Meeting 2019.

7 AMCP 2019 Highlights

On the Horizon: The -- How does this compare to current treatment options? Specialty Pharmacy Pipeline • Market share Specialty medications represent about 1.5% to 2.5% of prescriptions but comprise approximately 50% of total -- Will prescribers and patients prescription costs. The average cost of a specialty drug want the new treatment? is approximately $4,000, and specialty cost inflation has run between 11% of 15%. According to a study, 55% of -- Are there other viable treatment options employer respondents rated drug costs as their top concern, that payers will require first? and 71% said they do not feel that the current prices of orphan drugs are sustainable. • Treatment cost During a presentation at the AMCP Annual Meet- ing, Susan Trieu, PharmD, director of enterprise -- Is there anything else to treat this condition? specialty clinical solutions at MedImpact Health- care Systems, Inc., in Southlake, Texas, gave an Other factors to consider include the line of business overview of the specialty pharmacy pipeline. (commercial, Medicare, Medicaid), size of the plan, wheth- Dr. Trieu said that when considering the budget er it’s a genetic disease, regional differences, the need for impact, the following components are important: centers of excellence, and medical versus pharmacy costs. She then discussed some specialty drugs in the pipe- • Population line. An investigational chimeric antigen receptor T-cell therapy, bb2121, is in development for the treatment -- What does this new agent offer? of relapsed/refractory multiple myeloma. In a phase I study of heavily pretreated patients, there was a 95.5%

POSTER

respectively; in the tildrakizumab 200 mg group, Study Finds Tildrakinzumab Is Safe in Patients With the incidences were 62.7% (n=42) and 52.9% Metabolic Syndrome (n=139), respectively. The most common serious AEs in the tildraki- Metabolic syndrome is a combination of risk fac- studies: reSURFACE 1 and reSURFACE 2. The trials zumab 100 mg group for patients with metabolic tors related to cardiovascular disease and diabe- included adults with moderate-to-severe chronic syndrome were gastrointestinal and cardiac tes, including hypertension, dyslipidemia, elevated plaque psoriasis who continuously received disorders. In the tildrakizumab 200 mg group with fasting glucose, and central obesity. Patients with tildrakizumab 100 mg (n=369) or 200 mg (n=330) metabolic syndrome, the most common serious psoriasis may be at an increased risk for metabolic at weeks zero and four, as well as every 12 weeks AEs were injury/procedural complications and syndrome. thereafter to week 64 (reSURFACE 1) or week 52 nervous system disorders. For both doses, the The effect of metabolic syndrome on the safety (reSURFACE 2). Among the patients, 79 (21.4%) in incidences of fatal AEs were comparable between of biologic treatments is not well understood, so the 100 mg group and 67 (20.3%) in the 200 mg patients with (n=2) and without (n=2) metabolic researchers assessed the adverse event (AE) pro- group had metabolic syndrome. Baseline demo- syndrome. Metabolic status did not appear to file of tildrakizumab in patients with metabolic syn- graphics and disease characteristics were similar; result in worsening of diabetes. drome versus those without. They found that the however, patients with metabolic syndrome had safety of tildrakinzumab did not vary in patients higher median baseline weight, body mass index, The study was sponsored by Sun with metabolic syndrome and were consistent with and prevalence of cardiovascular disease and Pharmaceutical Industries, Inc. the known safety profile. The results of the study diabetes. were presented at the AMCP Annual Meeting dur- The most common treatment-related AE was Mehta NN, Lebwohl MG, Gottlieb AB, Mendelsohn AM, ing a poster session titled “Safety of Tildrakizumab infection, which occurred in similar incidences Parno J, Rozzo SJ, Menter AM. Safety of Tildrakizumab in Patients with Preexisting Metabolic Syndrome: among all treatment groups regardless of meta- in Patients with Preexisting Metabolic Syndrome: Post Post Hoc Analysis of 2 Phase 3 Clinical Studies bolic status, according to the researchers. In the Hoc Analysis of 2 Phase 3 Clinical Studies (reSURFACE (reSURFACE 1 and reSURFACE 2).” tildrakizumab 100 mg group, the incidences of 1 and reSURFACE 2). Abstract L10. Presented at The post-hoc analysis included data from two infections in patients with and without metabolic the AMCP Managed Care & Specialty Pharmacy Annual Meeting, March 25-28; San Diego, CA. phase III, double-blind, randomized, controlled syndrome were 50.6% (n=40) and 53.1% (n=154),

8 overall response rate in the 22 patients who received III clinical trial data, pharmacoeconomic data, and patient- the highest dose, including a 50% complete response reported outcomes prior to a product’s approval and launch. rate. The median progression-free survival was 11.8 This communication can provide benefits to both pay- months. Many patients (63%) experienced cytokine ers and manufacturers, as plans can more accurately release syndrome, and 33% of patients experienced neu- forecast formularies and manufacturers can provide rotoxicity. If approved, this drug may launch in 2020. factual, accurate, and nonmisleading information on Risdiplam is an investigational oral agent for the treat- products or indications that are not yet approved, ac- ment of spinal muscular atrophy (SMA). In the phase II/ cording to Elisabeth Brisley, MPH, legislative analyst III FIREFISH study that included patients with type 1 at AMCP, who delivered a presentation on the topic at SMA, 95% (n=20/21) were event-free at 10.5 months. In the AMCP Annual Meeting, along with Amy Duhig, the phase II/III SUNFISH study that included patients PhD, vice president of consulting services at Xcenda, with type 2 and 3 SMA, 63% of patients (n=19/30) had LLC, in Palm Harbor, Florida, and Sheila M. Thomas, improvement of three or more points in motor function PharmD, global head of patient insights and engage- measure at 12 months. No patients have discontinued ment strategy at Sanofi, Inc, in Bridgewater, New Jersey. treatment due to adverse events (AEs). In the FIREFISH Dr. Duhig discussed the findings of a survey of 47 trial, 10 patients (48%) had at least one serious AE, and U.S. payers to gauge their opinion on preapproval in- two patients died due to disease progression. In the formation exchange. The survey included 30 questions, SUNFISH trial, six patients (11.8%) had at least one and respondents included payers from managed care serious AE. The sponsors plan on filing 2H in 2020. organizations (66%) and pharmacy benefit manag- Valoctocogene roxaparvovec is an adeno-associated ers (26%). More than half (57%) were part of regional virus-factor VIII vector gene therapy in development for plans, and many (62%) were pharmacy directors. Com- the treatment of adults with severe hemophilia A with no bined, the respondents covered 203 million lives. inhibitors. In a phase I/II trial of nine adult patients, the The researchers found that the most important types high-dose cohort (n=7) saw increased factor VIII levels, of preapproval information were product pricing infor- which was maintained one year after infusion. The high- mation (89%), study results (77%), possible timelines for dose cohort had an annualized bleeding rate that decreased Food and Drug Administration (FDA) approval/clear- from 16 events to one event after the gene transfer. No ance/licensure (77%), and indication information (74%). patients developed inhibitors to factor VIII or thrombosis. Some respondents (40%) said the frequency of this type Seven patients experienced an increase in alanine amino- of information has increased, but most (68%) said the transferase levels with resolution. The manufacturer plans quality of the information has remained the same. to file via accelerated approval this year or next year. Payers reported some gaps in the communication, Specialty spend will continue to increase due including topics such as plans for further trials/subgroup to a very active pipeline, Dr. Trieu concluded, not- analyses, pricing, place in therapy, other indications in ing that the impact on payers will vary based on pursuit, health resource utilization/outcomes data, dos- the size of the treatable population and plan. ■ age strength/product size, and more. Approximately half of those who perceived a proactive information gap Presentation B8: Budgeting for the 2021 Specialty said that formulary decision-making could be improved Drug Spend. AMCP Annual Meeting 2019. if this gap were closed. Many respondents said the preferred timing of proactive information is six months prior to approval. A majority (93%) said their preferred source of this information is a medical science liaison. Dr. Thomas then provided outcomes from a survey of 41 Best Practices for Navigating U.S. manufacturers to gauge their opinion on preapproval information exchange. The survey included 10 questions, Preapproval Information and respondents were from small- to large-sized companies, most (56%) of which conducted health economics and Exchange outcomes research. Respondents were split when asked Preapproval information exchange is the if there was a process in place to deal with preapproval communication between biopharmaceutical companies and information exchange materials: 37% said yes, while population health decision-makers on topics such as phase 39% said no, but a process was under development. Most

9 AMCP 2019 Highlights

said they shared information through an account man- type of material and provide timely updates when infor- ager (67%) and health economic outcome liaison (60%). mation has changed. Lastly, flexibility is a necessity! ■ She then discussed best practices for delivering a credible message: “The focus should not be on who Presentation F4: The Road to Pre-Approval Information Ex- but should be on the what and ensuring appropri- change: Where Are We Today? AMCP Annual Meeting 2019. ate skills and competencies of individuals delivering the information.” Dr. Thomas’ tips include:

• Know your audience How to Manage Generics • Desirable skills and competencies are similar pre- and post-approval When They Become Too

• Job title will likely vary based on size Costly and structure of manufacturer There is insufficient competition in the generic drug marketplace, and market consolidation has led to price • May require a team of individuals with increases. Because of a lack of appropriate alternatives for complementary areas of expertise these therapies, generic drugs may be expensive. However, shifting utilization to lower-cost alternatives can produce • Labels of “promotional” versus “nonpromotional” considerable plan savings. personnel should not limit the ability to communicate During a presentation at the AMCP Annual Meeting, Sara Carruth, PharmD, manager of health econom- • Individuals should be trained to communicate ics and outcomes at MedImpact Healthcare Systems, at the top of their scope of practice Inc., in San Diego, California, and Alan Lukazewski, RPh, CDE, CGP, director of clinical pharmacy at Dr. Thomas said that it is important to stay educated NeuGen Health in Madison, Wisconsin, discussed on the latest FDA Final Guidance surrounding this type strategies for managing this expense and successfully of communication. Firms should develop and implement transitioning patients to lower-cost alternatives. a robust internal training plan for communicating this To manage high-cost generics, payers can increase member cost-sharing for these agents, creating an incen- tive to switch to lower-cost alternatives. Payers should identify clinically relevant, lower-cost therapies and engage in multichannel communication with the member, prescriber, and pharmacy to discuss alternatives. When comparing alternatives, plans should consider total drug spend, cost per unit, cost per claim, cost per 30-day supply, and change in cost. To identify lower-cost alternatives, rank the generic drugs by total cost or total plan paid at formulation level and filter for those meeting the pre-defined cost threshold. Then, examine other drugs in the therapeutic class and indication; the costs should also be verified at the individual strength level, as this can differ and may not result in cost savings. However, once a change is made, the dynamic nature of the generic marketplace requires continuous monitoring of prices and costs. Members may not be interested in switching medications: In a survey published in the American Journal of Managed Care, 53.6% of members self-reported that they would rather

10 medication, while 26.0% said they switched to a medication on formulary. However, a copay differential can be a management strategy. According to MedImpact data, a greater proportion of members switched to a lower-cost Utilization management alternatives when there was a larger copay differential. Utilization management strategies, such as uptiering, strategies, such as uptiering, step step therapy, and benefit exclusion, along with communication outreach can also help move members to therapy, and benefit exclusion, lower-cost alternative treatments. Future directions for communication of these changes can include real-time along with communication prescriber notification of lower-cost alternatives through e-prescribing, outreach through text message and outbound outreach can also help move calls, and optimizing member cost-sharing incentives. ■ members to lower-cost Presentation F7: Generic Trend Management: Decreasing High Cost Generic Spend by Shifting alternative treatments. Utilization. AMCP Annual Meeting 2019.

drugs have already been approved: caplacizumab-yhdp Specialty Drug Growth (for acquired thrombotic thrombocytopenic purpura), turoctocog alfa pegol (for hemophilia A), esketamine Continues: A Look at the (for depression), and brexanolone (for depression). Dr. Tharaldson then provided an extensive look at projected Pipeline approvals for the top specialty pharmaceutical drug classes. Key specialty pharmaceuticals market trends include Inflammatory conditions are the leading therapy class increased competition along with cancer and orphan drug based on per-member, per-year spending ($153 billion). development, according to Aimee Tharaldson, PharmD, The pipeline includes: senior clinical consultant of emerging therapeutics at Express Scripts in Woodbury, Minnesota, who gave a • Risankizumab, an interleukin (IL)-23 presentation at the AMCP Annual Meeting. inhibitor for psoriasis (expected 2019) In the past four years, a number of specialty drug generic options have been approved, representing $14 • Upadacitinib, a JAK-1 inhibitor for billion in overall U.S. spending opportunities, with rheumatoid arthritis (RA; 2019) the potential for $24 billion in expected specialty generics in the next five years. Through 2023, 71 • Ustekinumab, an IL-12 and -23 inhibitor specialty therapy patents will expire, representing for ulcerative colitis (2019) a $55 billion market opportunity. In addition, the biosimilar market keeps growing, as seven more • Bimekizumab, an IL-17A and -17F agents are projected to be approved this year. There inhibitor for psoriasis (2020) has also been extensive oncology drug development over the past seven years, with 2017 and 2018 see- • Filgotinib, a JAK-1 inhibitor for RA, ulcerative ing increasing growth after a slowdown in 2016. colitis, and Crohn’s disease (2020) The orphan drug pipeline, however, is experienc- ing extensive growth, as these agents represent more Various multiple sclerosis (MS) medica- than half (53%) of the current specialty pharmacy tions are in development, including: pipeline. Food and Drug Administration approvals for the agents continue to grow in comparison with tra- • Cladribine, a nucleoside analog that depletes B and ditional drugs. In quarter one of 2019, four specialty T lymphocytes for relapsing MS (RMS; 2019)

11 AMCP 2019 Highlights

• Siponimod, a sphingosine 1-phosphate receptor market has seven medications in the pipeline, which modulator for secondary progressing MS (2019) could result in approvals between 2020 and 2022. Lastly, Dr. Tharaldson discussed some • Diroximel fumarate, a monomethyl unique pipeline drugs, including: fumarate prodrug for RMS (2019) • Romosozumab for postmenopausal osteoporosis • Ozanimod, a sphingosine 1-phosphate receptor modulator for RMS (2019) • Onasemnogene for spinal muscular atrophy

• Dimethyl fumarate, a monomethyl • Bremelanotide for hypoactive sexual desire disorder fumarate prodrug for RMS (2020) • Celiprolol for vascular Ehlers-Danlos syndrome A number of oncology products are in development and are projected to be approved • Tafamidis for transthyretin cardiomyopathy before the end of the year, including: • Afamelanotide for erythropoietic protoporphyria • Erdafitinib for urothelial cancer • Fenfluramine for Dravet syndrome • Quizartinib for acute myeloid leukemia • Golodirsen for Duchenne muscular dystrophy ■ • Selinexor for multiple myeloma Presentation P1: Specialty Pharmaceuticals in • Pexidartinib for tenosynovial giant cell tumor Development. AMCP Annual Meeting 2019.

• Entrectinib for NTRK-fusion+ solid tumors

• Polatuzumab for diffuse large B-cell lymphoma Real-Time Benefit Checks • Darolutamide for prostate cancer May Improve Medication • Fedratinib for myelofibrosis Adherence, Reduce Patient In addition, four new HIV medications are ex- Costs pected to be approved within the next two years, including dolutegravir/lamivudine, cabotegravir/ Providers often have a limited knowledge of a specific rilpivirine, fostemsavir, and leronlimab (PRO-140). patient’s insurance coverage when prescribing medications, The nonalcoholic steatohepatitis pipeline for 2020 and a real-time benefit check program may be a solution and beyond is extensive as well, with 11 phase II and for this. Real-time benefit checks can provide information phase III drugs pending approval. This is particularly on coverage (quantity limits, prior authorization, step important, as current treatment options are limited; therapy), channel options (retail, mail order, specialty), most recommendations for treatment are focused on patient payment details, and alternative drugs based on the weight, diet, and exercise. However, these new treat- patient’s plan formulary. ment options come with many unknowns, includ- During a presentation at the AMCP Annual ing a steep projected price of $3,000 to $70,000 per Meeting, Jacqueline Hager, BS, product manager at year. It remains to be determined which patients Surescripts in Minneapolis, Minnesota, and Roger G. will be prescribed the medications and which will Pinsonneault, RPh, vice president of product innovation remain on a diet and exercise-focused regimen. at Gemini Health in Alpharetta, Georgia, discussed There are nine medications pending approval different options and implementation strategies for for Alzheimer’s disease, which are projected for ap- real-time prescription benefit check programs. proval in 2021 to 2024 and beyond. The hemophilia

12 This program uses a standard format to exchange POSTER data between providers and pharmacy claims proces- sors in real time. Providers, prescribers, or the pharmacy Study Finds Tildrakizumab originate a request from their practice management system. The pharmacy claims processor adjudicates the May Decrease Cardiometabolic requests and communicates a response in real time. The Symptoms in Patients With practice management software receives the response Psoriasis and presents the details in the provider’s workflow. Patients with psoriasis have a higher prevalence of cardiometabolic The proposed Medicare Part D rule for 2020 seeks to risk factors associated with metabolic syndrome, including major make revisions to the Medicare Advantage program (Part C) adverse cardiovascular events, obesity, hypertension, and diabetes. and Prescription Drug Benefit Program (Part D) regulations Researchers assessed the impact of tildrakizumab on cardiometa- to support health and drug plans’ negotiation for lower drug bolic factors in patients with psoriasis with and without metabolic prices and reduce out-of-pocket costs for enrollees. A real- syndrome. time benefits tool can provide patient-specific cost-sharing The study found that changes in cardiometabolic disease risk factors following treatment with tildrakizumab were generally con- information within the prescriber’s electronic health record. sistent regardless of metabolic syndrome status. The results of the Providers can identify a patient’s specific benefit plan and study were presented at the AMCP Annual Meeting during a poster assess utilization management tools that are included. session titled “The Effect of Tildrakizumab on Cardiometabolic Risk According to the Medicare guidance, these tools Factors in Psoriasis by Metabolic Syndrome Status: Post Hoc Analy- “should not be used by providers to evaluate alterna- sis of 2 Phase 3 Trials (reSURFACE 1 and reSURFACE 2).” tives for drugs prior to discussing whether the patient The post-hoc analysis included data from two phase III, intends to self-pay for the prescribed drugs. Health care double-blind, randomized, controlled studies: reSURFACE 1 and reSURFACE 2. The trials included adults with moderate-to-severe providers … should ensure that individuals are aware chronic plaque psoriasis who continuously received tildrakizumab that information about services or treatment, such as a 100 mg (n=369) or 200 mg (n=330) at weeks zero and four, as future prescription, may be disclosed to the plan by the well as every 12 weeks thereafter to week 64 (reSURFACE 1) or tool and effectuate the individual’s disclosure restric- week 52 (reSURFACE 2). Among the patients, 79 (21.4%) in the tion request by refraining to use the tool in instances 100 mg group and 67 (20.3%) in the 200 mg group had metabolic in which the patient intends to self-pay in full.” syndrome. Baseline demographics and disease characteristics were According to research presented from Surescripts, the similar; however, patients with metabolic syndrome had higher median baseline weight, body mass index, and prevalence of average savings per prescription with the use of a real- cardiovascular disease and diabetes. time benefit check can range from $21 for cardiology to Following continuous treatment with tildrakizumab 100 mg or $228 for psychiatry. The speakers gave an example of 200 mg, mean changes and mean percentage changes from base- the use of this program in action: The prescriber se- line in cardiometabolic disease risk factors were generally consis- lects 90 capsules of cariprazine—an antipsychotic used tent regardless of metabolic syndrome status. In the tildrakizumab to treat schizophrenia or bipolar disorder—at a patient’s 100 mg group, patients with metabolic syndrome experienced preferred pharmacy. The real-time benefit check noti- clinically relevant numerical decreases in fasting glucose, triglycer- ides, and systolic blood pressure. Similarly, patients with metabolic fies the prescribed that this medication will cost the syndrome in the tildrakizumab 200 mg group experienced numeri- patient $1,775.84 but that it is available through their cal decreases in systolic and diastolic blood pressure readings. pharmacy benefit manager’s mail order pharmacy for Targeted, prospective studies may provide further understanding just $125. The prescriber then sends the prescription to of these finding, the researchers noted. the mail or pharmacy for added savings for the patient. The study was sponsored by Merck Sharp & Dohme Corp., a subsidiary When engaging with a real-time benefit check of Merck & Co., Inc, and Sun Pharmaceutical Industries, Inc. program, employ a team-based approach to discuss costs with the patient. Establish a process to docu- Mehta NN, Lebwohl MG, Gottlieb AB, Mendelsohn AM, Parno J, Rozzo SJ, ment cost concerns that the entire team can refer- Menter AM. The Effect of Tildrakizumab on Cardiometabolic Risk Factors in ence, and train your team to have financial conversa- Psoriasis by Metabolic Syndrome Status: Post Hoc Analysis of 2 Phase 3 Trials (reSURFACE 1 and reSURFACE 2). Abstract L9. Presented at the AMCP Managed tions with the patient, the speakers concluded. ■ Care & Specialty Pharmacy Annual Meeting, March 25-28; San Diego, CA.

Presentation V7: Regulation to Outcomes: The Impact of Real-Time Prescription Benefit Check. AMCP Annual Meeting 2019.