Biosimilar Drug Landscape

Transcription

1 Biosimilar Drug Landscape

2 Biosimilars: Incorporating Use into Practice and Clinical Implications for Pharmacists Jessica Farrell, PharmD. Clinical Pharmacist- The Center for Rheumatology, LLC Associate Professor, Department of Pharmacy Practice Albany College of Pharmacy & Health Sciences Albany, NY

3 FACULTY DISCLOSURE The faculty reported the following financial relationships or relationships to products or devices they or their spouse/life partner have with commercial interests related to the content of this CE activity: - Jessica Farrell Nothing to Disclose

4 Objectives Evaluate clinical practice implications for pharmacists surrounding biosimilar use with a focus on agents used in gastrointestinal and rheumatic diseases Recognize core knowledge and skillset needed to prepare pharmacists to incorporate biosimilar use routinely into clinical practice

5 Reference Product Infliximab State of Affairs FDA Approved Biosimilar Approval Date # In Development Clinical Use Status CT-P13/infliximab-dyyb Infliximab-abda Infliximab-qbtx 05/05/ /21/17 12/13/17 Etanercept GP2015/etanercept-szzs 08/30/ (Phase III & Preclinical) 6 (Phase III) Marketing Launch 2018 Adalimumab ABP-501/adalimumab-atto BI695501/adalimumab-adbm 09/23/16 08/29/ (Phase I & III) Launch 2018 (?) Rituximab (CT-P10/GP2013 accepted for FDA review) -- 4 (Phase I & III) Launch? Bevacizumab bevacizumab-awwb 12/21/ (Pre-clinical & Phase I-III) Trastuzumab trastuzumab-dkst 12/1/17 4 (Pre-clinical & Phase I-III) Launch? Launch?

6 Approved Indications and Extrapolations Biosimilar Infliximab-dyyb Indications* AS**, CD (fistulizing, adult), CD (adult, ped 6yo+), Ps, PsA, RA (+MTX)**, UC Infliximab-abda AS, CD (fistulizing, adult), CD (adult, ped 6yo+), Ps, PsA, RA (+MTX)**, UC Adalimumab-atto AS, CD (adult), JIA (4yo+), Ps**, PsA, RA**, UC Adalimumab-adbm AS, CD (adult), JIA (4yo+), Ps, PsA, RA**, UC Etanercept-szzs AS, JIA (2yo+), Ps**, PsA, RA Ankylosing spondylitis (AS), Crohn's disease (CD), Plaque psoriasis (Ps), Psoriatic arthritis (PsA), Rheumatoid arthritis (RA), Ulcerative colitis (UC), Juvenile idiopathic arthritis (JIA) *Indications are from each product's package insert **Studied indication (all other indications are approved based on extrapolation)

7 KM 36 yo male, 15-year hx of CD 6 months ago he was experiencing diarrhea and abdominal pain unresponsive to prednisone and 6-MP A colonoscopy shows stage i3 lesions in the neoterminal ileum Started on infliximab 5mg/kg IV q8 weeks within 2 weeks, his disease responded to treatment Completely taper prednisone and was continued on 6-MP He reports just 3 bowel movements daily with no abdominal pain

8 KM 36 yo male, 15-year hx of CD He received a letter from his insurance about a new biosimilar for infliximab He has the following questions: If I switch, will it control my disease the same way? Will I have any side effects if I switch? Will it cost me less?

9 Interchangeability 351(k) required conditions for interchangeability designation: Biosimilarity established Produces same clinical result in any given patient Risk in terms of safety or efficacy of alternating or switching is not greater than risk of using innovator product without alternation or switch Definition: Product that may be substituted for the reference product without the intervention of the healthcare provider who prescribed the reference product. Substitution dependent on state law FDA. Considerations in Demonstrating Interchangeability with a Reference Product: DRAFT Guidance. Web. Accessed April 7, 2018.

10 Interchangeability Guidance Draft guidance released by FDA January 2017 Scope: Data/information needed to demonstrate interchangeability Key design and analysis requirements of a switching study or studies to support interchangeability Recommendations regarding use of innovator product in a switching study or studies Considerations for presentations, devices, closure systems for proposed interchangeable products Pathway not finalized No manufacturer has sought interchangeability yet FDA. Considerations in Demonstrating Interchangeability with a Reference Product. Guidance for Industry. Web. Accessed April 7, Bridges et al. Arthritis Rheumatol. 2018;70(3):

11 Cauchi R. State Laws and Legislation Related to Biologic Medications and Substitution of Biosimilars. state-laws-and-legislation-related-tobiologic-medications-and-substitutionof-biosimilars.aspx 2018.

12 Commonality in State Legislation FDA Approval Any biological product under consideration for substitution must first be approved as "interchangeable" by FDA. Prescriber Decides The prescriber would be able to prevent substitution by stating dispense as written or brand medically necessary. "Notification" vs "Communication" In bills enacted in , the language usually required that the prescriber "must be notified" of any allowable substitution made at a pharmacy. In 2015 the language commonly has been adjusted to say "communicate with," allowing a notation in an electronic medical record (EMR), PBM records or "pharmacy record that can be electronically accessible by the prescriber." Patient Notified? The individual patient must be notified that a substitute or switch has been made; this provision is included in at least 12 states. In some cases, state law would require patient consent before any such switch is made. Cauchi R. State Laws and Legislation Related to Biologic Medications and Substitution of Biosimilars Bridges et al. Arthritis Rheumatol. 2018;70(3):

13 Commonality in State Legislation Records The pharmacist and the physician must retain records of substituted biologic medications. Immunity Some state legislation provides immunity for pharmacists who make a substitution in compliance with biologics state law. Web Lists The state must maintain a public or web-based list of permissible interchangeable products. Cost or Pricing Some legislation requires the pharmacist to explain the cost or price of the biologic and the interchangeable biosimilar. The enacted laws in Colorado, Georgia, Illinois, North Carolina and Texas require that any authorized or allowable substitution must have the lowest cost. Cauchi R. State Laws and Legislation Related to Biologic Medications and Substitution of Biosimilars Bridges et al. Arthritis Rheumatol. 2018;70(3):

14 International Recommendations for the Use of Biosimilars to Treat Rheumatologic Disease September 2017 Overarching Principles A. Treatment of rheumatic diseases is based on a shared decision-making process between patients and their rheumatologists. B. The contextual aspects of the healthcare system should be taken into consideration when treatment decisions are made. C. A biosimilar, as approved by authorities in a highly regulated area, is neither better nor worse in efficacy and not inferior in safety to its bio-originator. D. Patients and healthcare providers should be informed about the nature of biosimilars, their approval process, and their safety and efficacy. E. Harmonized methods should be established to obtain reliable pharmacovigilance data, including traceability, about both biosimilars and bio-originators. Kay et al. Ann Rheum Dis 2017 [epub]

15 American College of Rheumatology: White Paper on Biosmilars

16 ML 48 yo Caucasian male, hx of PsA PMH: PsA x 5 yrs, GERD x8 yrs, Hypercholesterolemia x 2yrs MEDS: Atorvastatin 40mg 1 tablet daily, MTX 2.5mg 5 tablets in morning and 5 at night on the same day once weekly, folic acid 1mg daily, diclofenac 200mg 1 tablet 3 times daily, omeprazole 20mg 1 capsule twice daily HPI: He complains of continued right ankle pain, notably when bearing weight as well as morning stiffness lasting approximately 45 minutes to 1 hour. He reports an improvement in symptoms since the last visit 3 months ago, when his methotrexate dose was increased, however his chief complaint remains to be the pain in his right ankle. A/P: MD would like to start a TNFi and initiates benefits investigation

17 ML 48 yo Caucasian male, hx of PsA CAN WE USE A BIOSIMILAR? WHAT ARE YOUR CONCERNS? WHAT ARE THE OPTIONS?

18 Biosimilar Safety FDA issued guidance which includes requirements for safety Biosimilar studies assess adverse events and ADAs FDA has not issued guidance on studies required for interchangeability US biosimilars are not designated as interchangeable Safety and immunogenicity profiles have been shown to be comparable across treatment groups ADA development lower in some trials with biosimilars Anti-drug antibodies (ADA) Braun et al. Expert Opin Drug Saf Mar;16(3):

19 Drift and Evolution Comparison of Pre- and Post-Change Batches of Etanercept Post-change Pre-change Pre-change Post-change Schiestl M et al. Nat Biotechnol. 2011;29(4):

20 Immunogenicity ADAs can cause infusion/injection site and hypersensitivity rxns ~13% of patients with IMIDs treated with TNFi developed ADAs Presence of ADAs was associated with a 67% likelihood of some reduction in clinical response; in RA reduction was 73% Use of concomitant immunosuppressives reduces likelihood of ADAs ADAs from reference product may cross-react with biosimilar Pharmacovigilance is critical to monitor immunogenicity concerns Anti-drug antibodies (ADA) Immune mediated inflammatory disease (IMID) Braun et al. Expert Opin Drug Saf Mar;16(3): Thomas et al. BioDrugs. 2015;29:

21 Biosimilar Switch Considerations Optimal Switching Study Design At least 1-way switch from originator to biosimilar Assessment of immunogenicity Sufficient washout b/w treatment Multiple switching- interchangeability studies Sufficient power and f/up period EGILITY study Etanercept-szzs vs reference etanercept 3 switches (6 week duration each) No loss of efficacy or increase ADEs Moots et al. Curr Rheumatol Rep. 2017;19:37 Griffiths et al. Br J Dermatol 2017;176:92838

22 Biosimilar Switch Considerations Decisions should be evidence-based (including real-world data) Treating MD decision on case-by-case basis Switching data should not be extrapolated Automatic substitution not recommended at this time Close monitoring post-switch (enrolled in registries) Moots et al. Curr Rheumatol Rep. 2017;19:37

23 Biosimilar Switch Considerations Previous adverse reactions Utility of ADA/serum drug level testing Benefits Investigation Pharmacovigilance: Enroll patients in national registries MedWatch reporting Anti-drug antibodies (ADA) Moots et al. Curr Rheumatol Rep. 2017;19:37

24 Transitioning and Changing Economic reasons/ preferred product Biosimilar to a reference product should be avoided if ADAs to reference product are present Open-label extension data should support no loss of efficacy or ADRs Importance of post-marketing surveillance/clinician reporting Bridges et al. Arthritis Rheumatol. 2018;70(3):

25 Considerations for Dispensing Pharmacists Medication/Prescribing Errors & Issues Naming/suffix associated with biosimilar names Knowledge of interchangeability status PBM requirements Burden of provider/patient notification requirements Patient confusion issues Lack of Patient History Previous therapy trials History of immunogenicity/ true allergy Lack of Laboratory Data History of anti-drug antibodies P&T Committees & Protocol Development/Updates Potential for high-maintenance Bridges et al. Arthritis Rheumatol. 2018;70(3): Kim AP. Hosp Pharm Nov; 50(10):

26 Economic Considerations

27 Role of Medicare Programs Medicare pays for drugs administered in outpatient clinics based on the average sales price, net rebates, and other discounts reported to the government, plus a fixed % Providers would usually be penalized for choosing a lower-cost drug because the markup on a lower price is smaller in dollar terms. BPCIA requires Medicare payment for biosimilars to include a fixed percentage based on the more-expensive reference biologic. Implemented a new payment policy for biosimilars that pay a blended average sales price for all biosimilars that share a common reference biologic drug, plus the fixed percentage of the moreexpensive reference biologic, as required by BPCIA. Medicare s payment approach could shift over time Not yet known whether private insurers are more aggressively incentivizing biosimilars through payment. Cauchi R. State Laws and Legislation Related to Biologic Medications and Substitution of Biosimilars

28 In the News Scott Gottlieb, FDA Commissioner, March 7, 2018: "Payors can also help us by doing more to educate clinicians about the safety and value of biosimilars, to encourage appropriate adoption. We ll know that we ve been successful when there s a biosimilar market that can sustain multiple competing biosimilar and biologic options. For instance, in an FDA analysis of the market for white-blood cell stimulating biologics which can help cancer patients fight off infections when they are taking chemotherapy we ve seen pricing relative to the incumbent biologic, Neupogen, decline by 34% after the approval of two competitors, with the competitors capturing nearly 50% of the market share, and saving payors $150 million annually." Biosimilar Cost Savings in the United States, Rand study: "We estimated the cost savings potential of biosimilars to be $54 billion over ten years using recent baseline data and transparent assumptions, with a lower- to upper-bound range of $25 billion to $150 billion. Actual savings will hinge on an evolving biosimilar regulatory and competitive landscape." [Rand study, 2017] Cauchi R. State Laws and Legislation Related to Biologic Medications and Substitution of Biosimilars

29 Cost to patient Efficacy Disease Control Safety Cost to health-care system

30 Key Takeaways Biosimilars provide opportunity for increased patient access to treatments and costsavings Safety of switching has yet to be fully demonstrated for long-term efficacy, safety and immunogenicity Opportunities for confusion and adequate disease control concerns Importance of pharmacovigilance programs

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