Regenerative Medicine: Impact of Convergence on Drug, Device, and Biologics Development


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Speaker Dr. Annemarie Moseley, CEO of Aggregate Therapeutics (Palo Alto) explores how drug-device combination products are altering the medical practice from development to regulation to treatment.
Part of the MaRS Emerging Technologies Event Series. More information on the series can be found here:

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Regenerative Medicine: Impact of Convergence on Drug, Device, and Biologics Development

  1. 1. Regenerative Medicine: Impact of Convergence on Drug, Device and Biologics Development Annemarie Moseley, PhD, MD Acting CEO, Aggregate Therapeutics, Inc.
  2. 2. It’s a new age….
  3. 3. <ul><li>Human cell, tissue, or cellular and tissue-based product (HCT/P) </li></ul><ul><li>Drug </li></ul><ul><li>Device </li></ul><ul><li>Biological product </li></ul><ul><li>Combination product </li></ul>Five Product Categories
  4. 4. <ul><li>Articles containing or consisting of human cells or tissues </li></ul><ul><li>Intended for implantation, transplantation, infusion, or transfer into a human recipient </li></ul><ul><li>Examples: bone, ligament, skin, dura mater, heart valve, cornea </li></ul>What is an HCT/P?
  5. 5. <ul><li>Product intended for use in the diagnosis, cure, mitigation, treatment, or prevention of disease; </li></ul>What is a Drug?
  6. 6. <ul><li>An instrument, apparatus, implement, machine, contrivance, implant, in vitro reagent, or similar article </li></ul><ul><li>Intended for use in the diagnosis, cure, mitigation, treatment, or prevention of disease; or </li></ul><ul><li>Which does not achieve its intended purposes through chemical action in man and which is not dependent upon being metabolized to achieve its primary purposes. </li></ul>What is a Device?
  7. 7. <ul><li>Virus (or gene therapeutic) </li></ul><ul><li>Therapeutic Serum </li></ul><ul><li>Toxin or Antitoxin </li></ul><ul><li>Vaccine </li></ul><ul><li>Blood, Blood Component, or Blood Derivative </li></ul><ul><li>Allergenic Product </li></ul><ul><li>Cellular Therapy </li></ul>What is a Biological Product?
  8. 8. What is a Combination Product? <ul><li>A combination product is a product composed of any combination of : </li></ul><ul><ul><ul><li>drug and a device </li></ul></ul></ul><ul><ul><ul><li>biological product and a device </li></ul></ul></ul><ul><ul><ul><li>drug and a biological product; </li></ul></ul></ul><ul><ul><ul><li>drug, device, and a biological product </li></ul></ul></ul>(DES) (Dermagraft)
  9. 9. Combination Products Include <ul><li>Two or more separate products packaged together in a single package or as a unit comprising: </li></ul><ul><ul><li>drug and device products, </li></ul></ul><ul><ul><li>device and biological products, </li></ul></ul><ul><ul><li>biological and drug products </li></ul></ul>
  10. 10. Combination Products Include Any investigational drug, device, or biological product packaged separately that according to its proposed labeling is for use only with another individually specified investigational drug, device, or biological product where both are required to achieve the intended use, indication, or effect. (MiniMed Pump)
  11. 11. Designated Agency To determine the agency with primary jurisdiction for the premarket review and regulation of a combination product, will be based on the primary mode of action of the product.
  12. 12. The Regenerative Medicine Triad <ul><li>Growth Factors </li></ul><ul><li>Cells </li></ul><ul><li>BioMaterials </li></ul><ul><li>Matrices </li></ul>
  13. 13. The Regenerative Medicine Duo <ul><li>Cells </li></ul><ul><li>Growth Factors </li></ul><ul><li>Delivery Devices </li></ul>
  14. 14. <ul><li>New and/or improved angiogenesis </li></ul><ul><ul><li>Proteins </li></ul></ul><ul><ul><li>Gene Therapy </li></ul></ul><ul><ul><li>Cell Therapy </li></ul></ul><ul><li>Improved outcome for tissue function </li></ul><ul><ul><li>Cell Therapy </li></ul></ul>Case Study: Cardiac Regeneration / Repair
  15. 15. Bone marrow stem cells … within 3 months researchers found that the pumping activity had increased…this work, although preliminary, has the potential to revolutionize the treatment of heart failure …. AHA advertisement in Time Magazine, 2004
  16. 16. Will one delivery approach fit them all? Bone Marrow Adult Stem Cells Myoblasts
  17. 17. Delivery Approaches for Biologicals <ul><li>Direct needle injection during open surgical procedure </li></ul><ul><li>Intracoronary delivery </li></ul><ul><li>Endomyocardial injection </li></ul><ul><li>Retrograde coronary venous </li></ul><ul><li>Tangential transvenous intramyocardial </li></ul><ul><li>Minimally invasive thoracoscopic epicardial injection </li></ul>Almost 10 years in development—none approved
  18. 18. FDA Responses: <ul><ul><li>Does balloon occlusion increase adhesion and migration of cells into myocardium? </li></ul></ul><ul><ul><li>By stretching the artery wall does the balloon cause potential arterial damage and stenosis? </li></ul></ul><ul><ul><li>Suitable for all indications and cell suspensions? Potential for “clogging” lumen and impact of flow rate? </li></ul></ul><ul><ul><li>Is cell viability / functionality adversely affected by lumen materials or by shear force? </li></ul></ul><ul><ul><li>Potential for catheter materials to adversely affect viability / functionality of cells? </li></ul></ul>
  19. 19. <ul><li>Cell and gene products characterized according to somatic cell and gene therapy guidelines </li></ul><ul><li>Biologic products will need to be studied for safety and efficacy </li></ul><ul><li>Both large and small animal models may be used depending on whether the studies are evaluating mechanism of action or device delivery </li></ul><ul><li>Preclinical studies must address role of local deposition, dose response, timing of delivery, differentiation and retention of biologic products </li></ul>Convergence: Impact on Biologics Development
  20. 20. <ul><li>Bench tested with biologic for compatibility </li></ul><ul><li>Tested in large animal preclinical models for safety of delivery </li></ul><ul><li>No devices are marketed today for delivery of therapeutics to the heart; no clear “predicate” devices </li></ul><ul><li>Will be approved as combination product with biologic for specific indication (BLA) </li></ul><ul><li>Partnerships between biologic and device manufacturers for product development strategies. </li></ul>Convergence: Impact on Device Development
  21. 21. Changing Trends <ul><ul><li>Previously, biologics development focused on : </li></ul></ul><ul><ul><ul><li>Oncology </li></ul></ul></ul><ul><ul><ul><li>Immunodeficiencies </li></ul></ul></ul><ul><ul><ul><li>Inherited Diseases </li></ul></ul></ul><ul><ul><li>Increasing development in : </li></ul></ul><ul><ul><ul><li>Neurology </li></ul></ul></ul><ul><ul><ul><li>Cardiovascular </li></ul></ul></ul><ul><ul><ul><li>Orthopedics </li></ul></ul></ul>
  22. 22. <ul><ul><li>Why? </li></ul></ul><ul><ul><ul><li>Increased focus on aging population </li></ul></ul></ul><ul><ul><ul><li>New means of delivery are being developed </li></ul></ul></ul><ul><ul><ul><li>New biomaterials </li></ul></ul></ul><ul><ul><ul><li>Shift by interventional physicians to the use of biological products (cardiologists, neurosurgeons, radiologists) </li></ul></ul></ul>Changing Development Trends
  23. 23. Investing in Convergence <ul><ul><ul><li>Intellectual Property </li></ul></ul></ul><ul><ul><ul><li>Partnering / Licensing </li></ul></ul></ul><ul><ul><ul><li>Development Timelines </li></ul></ul></ul><ul><ul><ul><li>Manufacturing and Quality </li></ul></ul></ul><ul><ul><ul><li>Regulatory Strategy </li></ul></ul></ul><ul><ul><ul><li>End-user / customer </li></ul></ul></ul><ul><ul><ul><li>Distribution channels </li></ul></ul></ul><ul><ul><ul><li>Reimbursement </li></ul></ul></ul>
  24. 24. Investing in Convergence Device which has been combined with drug? - Is the drug approved? Human safety? - Is the drug delivered via a polymer or other drug delivery vehicle? - Manufacturing GMP vs. existing quality systems and impact on cost and timing - Value proposition?
  25. 25. Investing in Convergence Delivery device? - Drug or biologic delivered? - Is there a predicate? - Is there an existing market? - Have you covered delivery of all drugs, biologics etc in IP claims - Value proposition?
  26. 26. Investing in Convergence Biologic? - Does the biologic require or have improved efficacy with local delivery? - Is local delivery more cost efficient? - Do distribution channels exist? - Does it need a newly designed delivery system or can it be delivered with existing device?
  27. 27. Risk Profile for Convergence Products <ul><li>Approved drugs Phase 3 Phase 1-2 NCE </li></ul><ul><li>Approved polymer Polymer formul. Polymer IDE Novel </li></ul><ul><li>Approved device clinical trials Predicate IDE </li></ul><ul><li>Approved indicat. Other indication Clinical trials Pre-clin </li></ul><ul><li>Existing customer New customer Market Adoption </li></ul><ul><li>Co-development Licensing—transfer Contract manuf In-house </li></ul><ul><li>Standard assay New assay No assay immeasurable </li></ul>RISK
  28. 28. Commercialization Target Product Profile -Indication -Patient Benefit -Asking price/cost of goods - Delivery -Reimbursement Potential It’s never too early!!
  29. 29. TIER 1 TIER 2 TIER 3 Pipeline REDUCED RISK THROUGH LEVERAGED PRODUCT APPROACH Synovo-Derm ATX-Derm ATX-CNS Diabetes Synovo-Joint ATX-Ortho Cancer DX Marketed material; Novel ATX cells + New Indication for improved formulation Synovo ATX cells RISK
  30. 30. Sg2 Healthcare intelligence 2006 Looking to the future—learning from the past!