Integrated Biosimilar Services. With you every stage of the process 30+ Studies covering early phase and phase III

Transcription

1 Integrated Biosimilar Services 30+ Studies covering early phase and phase III With you every stage of the process

2 A promising and evolving market 7 out of 10 of the best selling drugs in 2015 were biologics. As the number of biologic medicines going off patent increases, biosimilar medicines promise to be an attractive offering to healthcare organisations, physicians and patients by providing greater choice and, a more cost effective alternative. Biosimilars are relatively new to certain markets therefore sponsors need a partner who can provide an end to end solution with the insight to navigate an evolving regulatory environment and the operational and commercial challenges that arise. Insight and support at every stage of the process ICON provides a fully integrated approach to the development of biosimilar medicines. We offer strategic consulting to define the optimal development and commercial strategy coupled with the operational capabilities to conduct the requisite studies in an effective and timely manner. Specialist consultants will be with you at every stage of the process; from the selection of the target biologic, the characterisation of the structure, function of the molecule and process scale-up, phase I-III trial management leading to marketing authorisation, through to commercialisation. Biosimilars: Stages of the Process Drug Discovery Select the target biosimilar molecule Extensive Molecular Characterisation Programme Comparability to protein structure, function and quality versus reference product Preclinical In vivo and In vitro assays to confirm functional biosimilarity Animal studies to confirm PK and Toxicology/safety Manufacturing process development, scale-up and validation IND/CTA Submission Phase I Clinical Studies PK/PD comparability Phase III Safety/efficacy comparability, clinical Immunogenicity Pediatric Development *If applicable NDA/MAA Submission Review Decision Sponsor Answers Review Questions Post Marketing REMs Pricing and Market Access Patient Reported Outcomes Our service portfolio covers the range of services needed: Drug Development Early Phase Services and Clinical Pharmacology Phase III Clinical Research Services Bioanalytical Laboratories Regulatory Affairs Commercialisation & Outcomes Sponser/Regulatory meetings encouraged for scientific advice 2

3 Drug Development Consulting ICON has extensive knowledge and experience in drug development, that extends beyond strategic consulting. We also have the operational expertise and proven performance record to deliver your programme on time and within budget. Product Development Plans ICON can develop a product development plan, that either encompasses every aspect of product development or just a selected aspect of the product development based on requirements. Areas covered include: Market assessment Proposed target product profile Assessment of current regulatory landscape with respect to: Current and planned guidelines Reference product basis of approval Therapeutic area specifics for development Possibilities for regulatory agency engagement in target countries Functional strategic advice on: Quality (drug substance and drug product) data for development, clinical trial and market approval submissions Preclinical development evaluation of in vitro and in vivo studies supporting the proposed clinical studies and the extrapolation of indications Clinical trial design and structure (studies required, study design, risk management plan) Regional legislation applicable to the development programme and proposed market access Overview of local and regional agency activities and interactions Regulatory risk and mitigation assessment Submission strategy for individual territories Early Phase Services and Clinical Pharmacology ICON has a long established Clinical Pharmacology Unit (CPU) in San Antonio, Texas, which is ideally suited to performing early phase studies for biosimilar medicines. Our purpose built clinical research facility ensures both maximum control of subjects environment and operational flexibility. Our principal investigators have a combined 45 years of clinical research experience, including extensive experience in first-in-human biologics and biosimilar compounds. In addition, ICON has partnerships with clinical sites globally including but not limited to US, EU, Hong Kong, Brazil and Australia. Leveraging these partner sites, ICON places Phase I studies at the site that is right for the protocol, delivering consistent management across programmes. ICON s geographic footprint and flexible operational model allows us to leverage services and expertise where it is needed. Pharmacokinetic and Pharmacodynamic Modelling and Simulation ICON has expertise in the application of pharmacokinetic and pharmacodynamic (PD) modelling and simulation which is critical for the successful conduct of early phase biosimilar studies, Phase III studies and subsequent extrapolation of indications for biosimilar approval. Our specialists have developed population PK models for several biologics: Rituximab (Rituxan, MabThera ) Infliximab (Remicade ) Trastuzumab (Herceptin ) Bevacizumab (Avastin ) Additionally, models are currently being developed for: Etanercept (Enbrel ) Cetuximab (Erbitux ) Adalimumab (Humira ) Omalizumab (Xolair ) Abatacept (Orencia ) 3

4 Phase III Clinical Research Services The development of biosimilars presents a unique set of challenges. Biosimilars are complex molecules that require Phase I data to demonstrate PK comparability and Phase III data to demonstrate therapeutic equivalence to the originator. Site, investigator and country selection can be particularly challenging and patient recruitment difficult due to the unique features of these studies including; Limited knowledge or understanding of biosimilars Availability of approved therapies Ongoing clinical trials with new innovative products and/or biosimilars Lack of publication opportunities Availability of the originator (reference) product Lack of harmonisation of global regulatory procedures ICON has developed effective strategies to overcome these issues. Our experience and data driven expertise in country and site selection will aid in timely execution of your clinical trials. Customised digital educational materials for investigational sites, targeted patient recruitment campaigns and site and patient engagement programmes using proprietary technology combine to deliver effective solutions. Site Feasibility Applying leading edge technology and working with EMR vendors, we conduct feasibility studies to determine the right patient population and the right countries for the studies. During the feasibility assessment, a thorough appraisal of the landscape is performed to evaluate direct and indirect competition. In cases of direct competition (i.e. the same biosimilar study) ICON makes recommendations on alternatives to ensure the inclusion of the appropriate countries and sites. Site and Patient Engagement ICON s Firecrest, is a web based technology platform designed to enhance site engagement and support patient recruitment and retention. It provides a suite of innovative products that maximise investigator site performance and study management by delivering consistent study specific communications to support a trial throughout its duration. Some of the features that make it particularly supportive of biosimilar programmes include: Protocol specific multimedia video training Customised visit-by-visit guides for communicating all study-related procedures econsent and patient portal application to guide the patient through the clinical trial process more easily. Firecrest is an award winning solution and is already delivering impact in clinical trials 50% 56% 45% Lower protocol deviations per site Improvement in median screening rates for studies Reduction in total data queries 4

5 Bioanalytical Laboratories Pharmacokinetic and Immunogenicity Testing ICON supports method development, GCP/GLP compliant biosimilar assay validation and sample analysis for PK and immunogenicity/anti-drug antibody (ADA) testing. Our approach follows industry best practices and regulatory guidance. To ensure a true assessment of comparability between the originator and the biosimilar, standardisation of PK and immunogenicity assay formats is essential. ICON experts advocate the use of a single PK assay to quantitate both the originator and biosimilar. Based on our experience of supporting biosimilar programmes for diverse compounds and indications, we also recommend early and frequent communication with regulators to identify the appropriate immunogenicity approach. Extensive Experience Our Bioanalytical Laboratory has provided support for the following 11 biosimilar programmes since 2012 and has experience with regulatory filings in the US, EU and Korea. Abatacept Adalimumab Bevacizumab Cetuximab Etanercept Infliximab Omalizumab Pegfilgrastim Ranibizumab Rituximab Trastuzumab Using our depth of expertise in assays for biologics, we also have validated several ICON proprietary bioanalytical methods for the innovator products listed below. These have been used to support biosimilar programmes, standard of care and combination therapy testing, and leveraged to support assays for preclinical development programmes. Adalimumab Bevacizumab Cetuximab Etanercept Infliximab Peginterferon alfa-2a Rituximab Trastuzumab Supplementary validation testing is required to qualify biosimilar compounds into the assays and may also be necessary depending on therapeutic area. In addition to the validated assays, we have developed assay formats for several innovators that are available and can reduce time to sample analysis. Proven Quality In a recent 2015 FDA pre-approval inspection of our bioanalytical biosimilar work, no 483 was issued and the inspection results supported the marketing approval of a biosimilar in the US. Our scientists understand the challenges in assay development and can advise on strategies for success. Regulatory Affairs ICON s Regulatory team has extensive experience in providing guidance and operational support for the steps necessary to transition seamlessly from early development through to Marketing Authorisation Application (MAA) and/or Biological Licence Application (BLA). Our team has an outstanding record of obtaining agreement for development plans for biosimilar products with the key regulatory agencies, creating the clinical trial documentation necessary to support the timely initiation of clinical studies. 5

6 Commercialisation & Outcomes Biosimilars are generally expected to offer a competitive price advantage to appeal to healthcare organisations and payers which make them an attractive business opportunity. A critical component of market access planning is the ability to communicate an integrated proposition that will alleviate any potential concerns and optimise perceptions of value. ICON can provide guidance for the optimal value proposition and go-to-market strategies for biosimilars, including competitive analysis and commercial optimisation strategies. Pricing and Market Access Biosimilar developers need to prepare a comprehensive market access strategy. It is important that commercialisation success factors are integrated into the strategy at an early stage and are revisited often during development decision making. In preparation for market entry, biosimilar developers must offer a value proposition for their product that resonates with payers and other stakeholders who are influential in access and reimbursement related decisions. Commercialisation strategy services: Biosimilar pricing and market access strategy Landscape analysis and biosimilar stakeholder mapping Value proposition and value message development Environmental and policy forecasting Payer Engagement Payers (private, national, regional, state, and other reimbursement agencies, hospital stakeholders etc.) have a significant role in determining the type of access biosimilars will achieve and each payer has unique considerations when determining access for biosimilars. Understanding these considerations and addressing them accordingly through payer engagement strategies is critical to succeeding in the biosimilar marketplace. Our consultants can deliver comprehensive solutions for payer planning and engagement, ensuring the successful launch and ongoing management of a biosimilar. An integrated approach to payer engagement and communication includes market assessments, development of customised value messages and contracting strategies, and account management. Services provided: Innovative biosimilar pricing agreements and contracting strategy Payer negotiation strategy Forecast development for geographic and managed care approval process Development of integrated managed markets and brand plans Account management excellence Pricing process and infrastructure Biosimilar education and training Biologics will account for 20% of total worldwide pharmaceutical spending by 2017* *According to IMS Health 6

7 Trusted Experience ICON has a wealth of biosimilars experience built up over several years of working with many different clients. The following table presents a small but representative selection of our experience with biosimilars: Drug Development Consulting Phase I Phase I/II Biosimilar recombinant erythropoietin; product development planning, clinical trial design and protocol writing; discussions with EMA and FDA Biosimilar rituximab; product development planning, clinical trial design and protocol writing; discussions with EMA and FDA Biosimilar trastuzumab; product development planning, clinical trial design and protocol writing; discussion with EMA Biosimilar bevacizumab; product development planning, clinical trial design and protocol writing; discussions with EMA and FDA A multicenter, open-label, randomised, parallel-group study in healthy subjects to assess the comparability of a single subcutaneous dose of X delivered manually from a pre-filled syringe versus delivered by a delivery device An open-label, randomised, 2-period, 2-sequence crossover study to assess the PK bioequivalence of X administered to healthy subjects by subcutaneous injection using an autoinjector versus the Sureclick Autoinjector A randomised, open-label, single-dose, 3-arm, parallel group study to determine the PK of X and bevacizumab in healthy male subjects A randomised, single-blind, single-dose, 3-arm, parallel-group study to determine the PK equivalence of X and adalimumab in healthy adult subjects A pilot study and a main study investigating the bioequivalence of X manufactured from two different manufacturing production lines in male adult volunteers with octreotide administered three times during both periods A double-blind, randomised, parallel-group study to demonstrate the equivalent PK properties of a single intravenous dose of X and trastuzumab in healthy male subjects A study to compare and assess safety, PK/PD profiles and primary efficacy after intravenous infusion of rituximab injection and X injection in diffuse large B-cell lymphoma patients A randomised, double-blind, study comparing the pharmacokinetics and pharmacodynamics, and assessing the safety of X and rituximab in subjects with active rheumatoid arthritis on a background of methotrexate who have had an inadequate response to one or more TNF antagonist therapies Extension study evaluating treatment with X versus rituximab in subjects with active rheumatoid arthritis who have participated in other X trials A Phase III randomised, double-blind study Of X plus paclitaxel versus trastuzumab plus paclitaxel for the first-line treatment of patients with HER2-positive metastatic breast cancer Phase III A Randomised, Double-Blind Pharmacokinetic Study Of X Plus Taxotere And Carboplatin Versus Herceptin Plus Taxotere (Registered) And Carboplatin For The Neoadjuvant Treatment Of Patients With Operable HER2-Positive Breast Cancer A Phase 3, Randomised, Double-Blind Study Of X Versus Rituximab For The First-Line Treatment Of Patients With CD20-Positive, Low Tumor Burden, Follicular Lymphoma A Phase 3 Randomised, Double-Blind Study Of X Plus Paclitaxel-Carboplatin And Bevacizumab Plus Paclitaxel -Carboplatin For The First-Line Treatment Of Patients With Advanced Non-Squamous Non- Small Cell Lung Cancer 7

8 ICON plc Corporate Headquarters South County Business Park Leopardstown, Dublin 18 Ireland T: F: enquiries@iconplc.com ICONplc.com/biosimilars