Specialty pharmacy: The topic that won t stop growing.

Specialty pharmacy: The topic that won t stop growing. Employee Benefits Planning Association Grant Knowles, PharmD, CSP Ardon Health Specialty pharmacy Vice President of Operations June 4 th, 2015

Overview

Healthcare spending (past and future) $6,000 53% Billions $5,000 $4,000 $3,000 $2,298 $2,501 $2,701 $2,915 $3,273 $3,660 $4,142 $4,702 $2,000 $1,000 $0 CMS. National Health Expenditure Projections 2006-2022. http://www.cms.gov/research-statistics-data-and-systems/statistics- Trends-and-Reports/NationalHealthExpendData/downloads/proj2012.pdf

Prescription spending (past and future) 500 450 54% 426 Billions 400 350 300 250 236 255 263 262 295 331 373 200 150 100 50 0 CMS. National Health Expenditure Projections 2010-2020. https://www.cms.gov/nationalhealthexpenddata/downloads/proj2010.pdf CMS. National Health Expenditures Aggregate, Per Capita Amounts, Percent Distribution, and Average Annual Percent Growth: Selected Calendar Years 1960-2009. https://www.cms.gov/nationalhealthexpenddata/downloads/tables.pdf

Patent cliff generic relief $90 billion dollars in reduced spend over the last 5 years

Patent cliff generic relief Brand name (generic name) Uses Retail sales ($Mil) Lipitor (atorvastatin) High cholesterol 5,803 Plavix (clopidigrel) Prevention of arterial thrombotic events 5,020 Singulair (montelukast) Asthma, allergic rhinitis 3,823 Seroquel (quetiapine) Schizophrenia, bipolar disorder 3,549 Actos (pioglitazone) Type 2 diabetes 2,913 Cymbalta (duloxetine) Depression, fibromyalgia, chronic pain, diabetic peripheral neuropathy 2,891 Lexapro (escitalopram) Depression 2,590 Zyprexa (olanzapine) Schizophrenia, bipolar disorder 2,114 Concerta (methylphenidate ADHD 1,560 extended-release) Levaquin (levofloxacin) Bacterial infections 1,542 Diovan (valsartan) Hypertension, CHF 1,430 Diovan HCT (valsartan/hctz) Hypertension 1,430 TriCor (fenofibrate) Hypotriglyceridemia 1,123 Lidoderm (topical patch) Post-herpetic neuralgia 1,066 Geodon (ziprasidone) Schizophrenia 1,058 Provigil (modafinil) Narcolepsy, idiopathic hypersomnolence 1,014 Aciphex (rabeprazole) GERD, stomach ulcers 1,006 *First-time generics are subject to significant change as a result of multiple patent protections, patent litigation, pediatric or other exclusivities, at-risk launches, and delays between patent expiration and launch of first-time generics. IMS retail claims data [database online]. Fairfield, CT: IMS Health; 2014. http://www.imshealth.com.

Specialty prescriptions An undeniable and growing proportion of healthcare spend.

Defining

What is specialty medication? Certain pharmaceuticals, biotech, or biological drugs, which may be offered by PBM*, that are used in the management of chronic or genetic disease, including but not limited to injectable, infused, or oral medications, or products that otherwise require special handling. *PBM - Prescription Benefit Manager Chan, L (2009). Control Specialty Drug Cost By Making Your PBM Helpful. Managed Care. http://www.managedcaremag.com/archives/0908/0908.specialtydrugcost.html

Specialty medications 1% of prescriptions 25-35% of prescription spend 15-25% increase per year x 3 years 8 out of the top 10 medications in 2013 9 out of the top 10 prescription in 2022 Cost $311 PMPY in 2014 $7,000 - $400,000/member/treatment year 28 times more costly than non-specialty Drug Trend Report Express Script - 2014 EvaluatePharma. World Preview 2014-2020..

Specialty Parameters High Cost Complex admin Unique monitoring Specific climate needs Require additional patient education Require 24/7 clinical support Drugs not available in retail settings $1,000- $40,000 per Rx Injection, infusion REMS*, efficacy criteria Specific storage or shipment protocol hightouch disease states, adherence High sideeffects, adherence assistance LDD ± *REMS Risk Evaluation and Mitigation Strategies ± LDD Limit Distribution Drugs

How payers define specialty High Cost Requiring special monitoring Treats orphan disease Requires specialty handling Limited distribution Indicated for disease already classified as specialty 85% 81% 71% 73% 67% 66% Requires patient admin training From 91 payers with over 124 million lives EMD Serono Injectable Digest (10 th Edition). 43% 0% 20% 40% 60% 80% 100%

How payers define high cost 45% 40% 40% 35% 30% 29% 25% 20% 15% 10% 5% 14% 17% 0% From 91 payers with over 124 million lives EMD Serono Injectable Digest (10 th Edition). <$600 $600-$800 $1000-1200 >$1,200

Past & Future

Spending on traditional therapies will grow at slower rates. Specialty spend will experience hand-over-fist growth in the foreseeable future.

Specialty spend $140 $120 $ in Billions $124 $100 $80 $60 $40 $20 $55 $1.7 trillion spend by Specialty 2030, Spend estimates PCMA $0 2005 2014 IMS - Medicines Use and Spending Shifts April, 2015 PCMA - Pharmaceutical Care Management Association

Towering trends 25.0% 20.0% 22.6% 22.3% 21.3% 15.0% 10.0% 9.0% 10.3% 10.9% 5.0% 3.9% 4.3% 0.0% -5.0% -0.5% 2015 2016 2017 Traditional Specialty Overall Drug Trend Report 2014 Express Script

Price of medications PMPY $800 $700 $669 $665 $691 $721 $600 $566 $500 $400 $300 $311 $381 $466 $200 $100 $0 2014 2015 2016 2017 Traditional Specialty Drug Trend Report 2014 Express Script

Top 10 medications in 2010 Medication 2009 Sales in Billions BOLD Indicate Specialty Medications *Now generic products EvaluatePharma. World Preview 2016. May 2010. Available at: http://www.windhover.com/download/blog/ep0510worldpreview2016.pdf. Accessed August 30, 2011. 2010 Sales in Billions 1 *Plavix $5.5 $6.1 2 *Lipitor $5.6 $5.3 3 Advair $4.0 $4.0 4 *Seroquel $3.4 $3.7 5 Epogen/Procrit $3.8 $3.5 6 *Actos $3.2 $3.5 7 Abilify $3.2 $3.3 8 Enbrel $3.2 $3.3 9 *Singulair $3.0 $3.2 10 Remicade $3.0 $3.0

Top 10 medications in 2013 Product Generic Name Company 1 Humira adalimumab AbbVie 2 Lantus BOLD Indicate Specialty Medications EvaluatePharma. World Preview 2020. insulin glargine recombinant 3 Enbrel etanercept Amgen 4 Remicade infliximab Johnson & Johnson Pharmacologic al Class Anti-tumour necrosis factor alpha (TNFa) MAb 2013 2020 5,236 6,566 Sanofi Insulin 4,978 6,299 Tumour necrosis factor alpha (TNFa) inhibitor Anti-tumour necrosis factor alpha (TNFa) MAb 4,256 4,918 3,891 4,594 5 Rituxan rituximab Roche Anti-CD20 MAb 3,594 2,251 6 Neulasta pegfilgrastim Amgen Granulocyte colony-stimulating factor (G-CSF) Dipeptidyl peptidase IV inhibitor 3,499 2,640 Januvia/ sitagliptin 7 Merck & Co 2,946 3,255 Janumet phosphate 8 Avastin bevacizumab Roche Anti-VEGF MAb 2,780 2,130 Epogen/ 9 epoetin alfa Amgen + JNJ Erythropoietin 2,748 1,502 Procrit 10 Revlimid lenalidomide Celgene Immunomodulator 2,489 2,603

Top 10 medications in 2020 Product BOLD Indicate Specialty Medications EvaluatePharma. World Preview 2020. Generic Name 1 Humira adalimumab AbbVie 2 Lantus insulin glargine recombinant 3 Enbrel etanercept Amgen Company 4 Remicade infliximab Johnson & Johnson 5 Sovaldi sofosbuvir Gilead Sciences 6 Tecfidera dimethyl fumarate Pharmacological Class Anti-tumour necrosis factor alpha (TNFa) MAb 2013 2020 5,236 6,566 Sanofi Insulin 4,978 6,299 Biogen Idec Tumour necrosis factor alpha (TNFa) inhibitor Anti-tumour necrosis factor alpha (TNFa) MAb Hepatitis C nucleoside NS5B polymerase inhibitor Nuclear factor erythroid 2-related factor (Nrf2) pathway activator 7 Nivolumab nivolumab Bristol-Myers Squibb Anti-programmed 8 Eylea aflibercept Regeneron Pharmaceuticals 9 Imbruvica ibrutinib Pharmacyclics 10 Xtandi enzalutamide Astellas Pharma death-1 (PD-1) MAb 4,256 4,918 3,891 4,594 136 4,567 864 4,175-3,618 VEGFr kinase inhibitor 1,409 3,583 Bruton's tyrosine kinase (BTK) inhibitor Androgen receptor antagonist 14 3,564 442 3,337

Prescription spend distribution Prescription Spend in Billions 600 Billions 500 400 300 200 100 255 266 275 287 124 379 148 413 181 456 Expected double again by 2020 219 506 0 2014 2015 2016 2017 Traditional Specialty Total IMS - Medicines Use and Spending Shifts April, 2015 Drug Trend Report 2014 Express Script

Prescription spend distribution 2014 2015 2016 2017 Traditional Specialty Traditional Specialty Traditional Specialty Traditional Specialty 33% 36% 40% 43% 67% 64% 60% 57% IMS - Medicines Use and Spending Shifts April, 2015 Drug Trend Report 2014 Express Script

Why so special?

Why so special? Treatment & cures for conditions that may have had none Serious benefits and serious potential for side effects Shifting therapies to patient administered More home, less hospital Oncology Biologics typically do not face generic competition after their original patent protection has expired, thus extending high prices indefinitely

Fueling the growth Large patient populations New indications for existing drugs Improved efficacy Large pipeline of new drugs Novel mechanisms Trend Price increases

Specialty pipeline 70% FDA approvals were specialty, 2012-2013 50% of approvals in 2014 >900 biologics, for more than 100 diseases >70% for cancer, infectious diseases, autoimmune diseases, and cardiovascular disease 37% monoclonal antibodies or therapeutic proteins (e.g. Humira, Enbrel) Focus on small (orphan) populations (e.g. Sensipar, Soliris) Pharmaceutical Research and Manufacturers of America.. EMD Serono Specialty Digest, 10 th Edition

Acute become chronic 40% 35% 30% 25% 20% 15% Projected Percentage Increase in Cancer Survivors Between 2010 and 2020 36% 30% 25% 13% 32% 10% 5% 0% Prostate Cancer Lymphoma Breast Cancer Colorectal Cancer All Types Source: Mariotto AB, Yabroff KR, Shao Y, et al. Projections of the cost of cancer care in the United States: 2010-2020. Journal of the National Cancer Institute. 2011; 103(2):1-12

Growing population Millions 120 100 80 60 40 20 0 U.S. Population 55 years and over 31.5% 28.2% 24.7% 97.8 87.4 76.5 2010 2015 2020 # of people % of population 35% 30% 25% 20% 15% 10% 5% 0% % of population U.S. Census Bureau, "2008 National Population Projections," August 2008.

Price increases 20.0% 18.0% 16.0% 14.0% 12.0% 10.0% 8.0% 6.0% 4.0% 2.0% 0.0% Average Annual Increase Since 2007/2008 17.6% 17.5% 9.8% 9.8% 10.5% Copaxone Enbrel Humira Forteo Rebif

Where s the generics? Trick question, there aren t any

Size & Complexity Small molecule drugs & Proteins Small Molecule Drug Aspirin 21 atoms Large Molecule Drug hgh ~3000 atoms Large Biologic IgG Antibody ~25,000 atoms Complexity Size Bike ~21 lbs.. Car ~3000 lbs. Business Jet ~30,000 lbs. (without fuel) http://www.fda.gov/drugs/drugsafety/postmarketdrugsafetyinformationforpatientsandproviders/ucm220037.htm

Slow biosimilars slow to market Made available by the Patient Protection and Affordable Care Act No abbreviated approval process like small molecule drugs Must demonstrate safety, purity, and potency to reference product with: Analytical Testing Bioassays Animal studies Human clinical studies FDA Purple book No clinically meaningful differences between biologic and reference product in terms of safety, purity, and potency Interchangeable biosimilars may be substituted for the reference product by a pharmacist without intervention from the prescribing physician http://www.fda.gov/drugs/developmentapprovalprocess/howdrugsaredevelopedandapproved/approval Applications/TherapeuticBiologicApplications/Biosimilars/ucm411418.htm

Market impact - biosimilars Potential $44.2 billion reduction in spending from 2015 to 2024 New competition Reference product (brand) will not go away New delivery mechanisms Syringe vs. Pen Something cooler than what is out there First biosimilar was approved this year Zarxio to compete with Neupogen The Cost Savings Potential of Biosimilar Drugs in the United States

Specialty categories Rank Therapy Class Avg. Cost/Rx Medications Rx Per 1000 1 Inflammatory Conditions $2,913.33 Humira, Enbrel Stelara, 27 2 Multiple Sclerosis $4,510.06 Copaxone, Tecfidera, Avonex 12 3 Oncology $6,191.29 Gleevec, Revlimid, Capecitabine, Temozolomide 7 4 Hepatitis C $16,373.40 Sovaldi, Harvoni 2 5 HIV $1,138.48 Atripla, Truvada 24 6 Misc. $4,539.50 Botox, Xyrem 2 7 Growth Deficiency $3,852.58 Norditropin FlexPro, Genotropin 3 8 Hemophilia $7,519.16 Advate 1 9 Pulmonary Arterial Hypertension $4,023.23 Sildenafil, Adcirca, Tracleer 1 10 Transplant $208.00 Azathioprine, Mycophenolate, Tacrolimus, Prograf 25 PCSK9 estimates up to$100 billion annually spend 2014 specialty spend was $124 billion Drug Trend Report Express Script 2014 Blockbuster Drugs Fill 2015 Pipeline March 2015 Bold generics or soon to be generic

Focus

Specialty Zavesca Afinitor Hepatitis C Stelara Xiaflex Anticoagulants Ilaris Revatio Sutent Rituxan Promacta Cancer Tykerb Simponi Xyrem Procrit Revlimid Sprycel

Focused industry % spend of top 10 specialty classes Others 11% Top 10 89% Drug Trend Report 2014 Express Script

Focus % Makeup Inflammatory Conditions Multiple Sclerosis Oncology Hepatitis C HIV Misc. Specialty Conditions Growth Deficiency Hemophilia Pulmonary Arterial Hypertension Transplant 4% 3% 2% 2% 2% 9% 13% 12% 17% 26% Drug Trend Report 2014 Express Script 0% 5% 10% 15% 20% 25% 30%

Manufacturer attention Blockbusters require smaller populations $10.3B Sovaldi (Hepatitis C) Development cost of orphan drugs can be lower with a higher anticipated return Avg. orphan drug cost per patient per year $137,782 Avg. non-orphan drug cost per patient per year $20,875 New report shows orphan drug market to reach $176 billion by 2020. EvaluatePharma. New release. October 29, 2014 Succeeding in the rapidly changing U.S. Specialty market. https://www.imshealth.com/deployedfiles/imshealth/global/north%20america/united%20states/managed%20markets/5-29- 14%20Specialty_Drug_Trend_Whitepaper_Hi-Res.pdf

Managing specialty

Determining value 30%, 5-year survival Displaced prior therapy and drastically improved 5-year survival to 89% in CML Improves survival by 10 days when giving with the standard of care for pancreatic cancer. Gleevec Tarceva Prior Therapy for CML $43,100 per life-year saved $410,000 per life-year saved Fojo T, Grady C. How much is life worth: cetuximab, non small cell lung cancer, and the $440 billion question. Journal of the National Cancer Institute. 2009;101(15):1044-1048. CML = chronic myeloid leukemia

Financial Assistance Non-adherence: A $300B problem Non-adherence/persistence? Not starting therapy Not continually staying on therapy Does cost mattes? Evidence: 3.8% reduction in adherence for every $10 in patient cost Patients with a cost <$100 initiate therapy: 37% more than those with >$200 14% more than with $101-$200 Patients using financial assistance: 30% more likely of achieving an medication possession rate (MPR) >80%

Financial Assistance Ardon Health financial assistance for 2015: Avg. medication cost: $4,652 Avg. copay/coinsurnace: $292 Avg. assistance: $278 Avg. patient out-of-pocket cost: $14 Copaxone Avonex Rebif Gilenya Betaseron Pt Cost $0 $0 $0 $0 $0 Monthly Max Annual Max $2,500 - - - - $12,000 - $12,000 $12,000 $9,500 Types of funding Manufacturer assistance* Need based-assistance Charitable assistance *Government programs (Medicare & Medicaid) are not eligible for most manufacturer assistance

Cost share burden Hepatitis C. treatment = ~$94,000 for 12- weeks Multiple Sclerosis = ~$54,000/patient/year Coinsurance Patient Pay 10% - $9,400 20% - $18,800 30% - $28,200 40% - $37,600 50% - $47,000 Coinsurance Patient Pay 10% - $5,412 20% - $10,824 30% - $16,236 40% - $21,648 50% - $27,060

Top strategies Prior Authorization (PA) Limit to evidence-based uses. FDA approved indications Off-label: national clinical guidelines & peer-reviewed articles Step-therapy for conditions with multiple evidence-based treatment modalities Requires the use of cost-effective therapies prior to initiation Value-based cost share Exclusive specialty tiering Waste Mitigation: 30-day supply on all treatments options Consider lower supplies for therapies with high discontinuation rates (15 day) Selecting preferred specialty pharmacy partner

Benefit design strategies Strategies implemented or will be in 12 months Limit specialty products to 30-day supply 94% Equalize cost share between RX and medical benefits Create cost share tier for specialty 58% 55% Create specialty drug benefit for all drugs 44% Implement value-based benefit design Allow 90-day supply for stable patients 23% 30% Lower cost share to improve adherence From 91 payers with over 124 million lives EMD Serono Injectable Digest (10 th Edition). 12% 0% 20% 40% 60% 80% 100%

Benefit design strategies Strategies implemented or will be in 12 months Develop stricter PA for some non-preferred drugs Create coverage guidelines across RX and medical benefit Require trial of 1 preferred drug before nonpreferred Select preferred drugs by indication Require trial of >1 preferred drug before nonpreferred Require trial time of preferred drug before non-preferred 91% 91% 87% 81% 72% 73% Exclude coverage of some non-preferred products From 91 payers with over 124 million lives EMD Serono Injectable Digest (10 th Edition). 52% 0% 20% 40% 60% 80% 100%

Specialty, Pharmacy? US population ~320 million Typical retail pharmacy dispenses: Specialty pharmacy, experience: ~0.9/RX /patient/month ~1,075 RX/week ~500-5000 specialty RX/week Specially RX s are ~1% ~11 specialty Rx/week Specialization # of US pharmacies ~67,000

Making it Right Right medication Right dose Right time Is it appropriate to start? Is it appropriate to continue? Is it the initiation of therapy? Is it continuation of therapy? Is it being taken it? Is it at the correct frequency? Specialty medication can make up 80% or more of a patient s health care spend

Proactive adherence management Provide disease specific patient education & management Reimbursement and eligibility coordination Specialty Services Provide 24/7 access to RN or pharmacist Preventative measures for drug waste, abuse and misuse Ensure appropriate dose of medication Flexible shipping distribution direct to patient s home, business, or MD First-level claims denial and appeals processing Patient-assistance programs In-office, in-home training capability Audit capabilities Benefit design, formulary support Expertise in benefit investigations, prior authorization, appeals

Connectivity Connecting patient s with support programs Patient receiving injection training 40% more likely to have a MPR >80% 24/7 pharmacist support Advocacy groups Medication disposal services Case management integration

Continued Assessment/Counseling Every fill: Proactive refill call (at least 7 days) Adherence assessment Side effect assessment Appropriateness assessment Improved adherence Better outcomes Reduced waste Decreased side effects and increased knowledge Reduced premature discontinuation Reduced additional health cost Appropriateness check Proper patient outcomes Reduce waste

Waste mitigation Focus Target highly discontinued medications e.g. oral oncology Limited duration efficacy medications Partial fill programs Dispensing 14-15 day supply of therapy Duration of 1-3 months Increased healthcare touches Shown to save $1,000/patient Khandelwal N, Duncan I, Ahmed T, Rubinstein E, Pegus C. Impact of clinical oral chemotherapy program on wastage and hospitalizations. J Oncol Pract. 2011;14:e25s e29s. doi: 10.1200/JOP.2011.000301.

Compounds What is a compound? combining, mixing, or altering ingredients of a drug to create a medication tailored to the needs of an individual patient What s in the limelight? Topical pain compounds Why? High cost - $500-$10,000 AWP prices have risen substantially No MAC pricing 128% increase in trend in 2014 Intense marketing Can topical pain compounds be helpful? Limited evidence that the active ingredients, in combination, have been evaluated by the FDA for safety and/or efficacy Many include 10-15 different active ingredients combining products from the same drug class. 10-20 time the commercially manufactured medication. What s being done Restrictions on use and/or cost. Drug Trend Report Express Script 2014