Drug Delivery Technology: Revolutionizing CNS Therapies

Summary

"The World Health Organization has indicated that CNS disorders are the major medical challenge of the 21st Century, yet treatments for most CNS disorders are either inadequate or absent. The CNS is the most challenging frontier for drug discovery largely because of the complexity of the brain and the existence of the BBB"

Alan Palmer, Chief Executive of Pharmidex, UK

The revenue derived from Central Nervous System (CNS) drugs is vast, in that such a large number of diseases and disease processes are grouped under the CNS "umbrella". These include acute organic conditions, such as infection, pain (both acute and chronic); chronic organic conditions such as neoplasms, seizure disorders; chronic degenerative disorders such as multiple sclerosis, Parkinson's disease, Alzheimer's disease, and other dementias, as well as the range of functional disorders classified as mental illnesses: schizophrenia, affective and anxiety spectrum disorders, attention deficit hyperactivity disorder (ADHD), sleep disorders and addictions.

The CNS has always posed problems in terms of drug delivery, drug efficacy and safety/ tolerability because of the presence of the blood brain barrier (BBB). The BBB is composed of a layer of extremely tightly packed epithelial cells, saturated with enzymes designed to protect the brain by disallowing the entry of noxious substances via the bloodstream. The unfortunate by-product of this has been the problem of delivering beneficial drugs to the CNS in sufficient quantities to effectively treat the targeted condition without causing unacceptable systemic adverse reactions.

Administering drugs directly into the CNS e.g. intrathecally or intracerebrally, is an effective method of delivery but carries significant risks in terms of infection as well as being invasive and unpleasant for the patient. In recent years, methods of by-passing the BBB have been proposed, trialed and are now available, such as osmotic permeability, the use of nanoparticles small enough to penetrate the BBB, ultrasonic adjunctive drug treatment, and stem-cell and gene therapy, which effectively provide a "self-cure" by promoting neuroplasticity and cell regeneration within the central nervous system itself.

Newer delivery methods such as transdermal drug delivery which can employ nanotechnology to increase absorption and bioavailability, as well as being non-invasive and simple to use are on the rise, and seem set to be used for a wide range of CNS disorders, including psychoses, pain and neurodegenerative disorders.

Contents

• 1 The CNS market: opportunities for novel delivery technologies
  • 1.1 Introduction
  • 1.2 Overview of the market
    • 1.2.1 Current market size
    • 1.2.2 Patient population
  • 1.2 Current CNS therapies
    • 1.2.1 Product drivers and dampeners
  • 1.3 CNS players & product pipeline
    • 1.3.1 Key pharma players
    • 1.3.2 Product pipeline
    • 1.3.3 Product pipelines: neurodegenerative diseases, chronic organic conditions
    • 1.3.4 Product pipeline: mental disorders, pain
  • 1.4 Growth areas for CNS drug delivery
    • 1.4.1 Penetrating the blood brain barrier
    • 1.4.2 Transdermal delivery
• 2 Market drivers and opportunities for drug delivery technologies
• 3 Key drug delivery companies and academic researchers in CNS drug delivery
• 4 Current CNS drug delivery issues and opportunities
  • 4.1 Delivery across the BBB
  • 4.2 Improving patients compliance
  • 4.3 Harnessing neuroplasticity
• 5 Invasive delivery technologies
  • 5.1 Small molecule nano-enabled delivery
    • 5.1.1 Case study: Paliperidone palmitate (Johnson & Johnson/Elan)
    • 5.1.2 Case study: DNA nanoparticles (Copernicus Therapeutics)
    • 5.1.3 Case study: Nanocells (Midatech)
    • 5.1.4 Case study: nab technology/Protosphere (Cenomed BioSciences)
  • 5.2 Vaccine delivery
    • 5.2.1 Case study: ProSavin (Oxford BioMedica)
    • 5.2.2 Case study: DCVax (Northwest Biotherapeutics)
    • 5.2.3 Case study: NicVax (Nabi Pharmaceuticals)
  • 5.3 Gene therapy delivery
    • 5.3.1 Case study: non-viral delivery (ArmaGen Technologies)
    • 5.3.2 Case study: viral vectors (Neurologix/ Cornell Medical College)
    • 5.3.3 Case study: Intracerebral delivery (Genzyme Corporation)
  • 5.4 Stem cell delivery
    • 5.4.1 Transplantation
    • 5.4.2 Drug delivery of stem cells
    • 5.4.3 Case study: NeuroGeneration
    • 5.4.4 Case study: Neural stem cells (Institute of Cellular Medicine)
    • 5.4.5 Case study: Neural repair cells (Aastrom / Tissue Repair Cell Technology)
  • 5.5 Peptide delivery
    • 5.5.1 Case study: Lipobridge technology (Genzyme Corporation / Pharmidex UK)
    • 5.5.2 Case study: "Design for Peptides" (Genzyme Corporation/ Brookwood Pharmaceuticals/SurModics)
    • 5.5.3 Case study: Nanobodies (Ablynx)
  • 5.6 Implants, pumps and electrical delivery systems
    • 5.6.1 Case study: Duros implant (ALZA/NiTi Medical Technologies)
    • 5.6.2 Case study: Intrathecal delivery devices (Medtronics)
    • 5.6.3 Case study: "Brain Gate" implants (Cybernetics Inc)
  • 5.7 Our opinion on invasive drug delivery technologies
• 6 Minimally invasive delivery technologies
  • 6.1 Ultrasound
    • 6.1.1 Case study: Catheter for stroke & ischemic stroke (EKOS / NeuroWave
    • 6.1.2 Case study: Ultrasonic delivery device (Perfusion Technology
  • 6.2 Convection enhanced delivery
    • 6.2.1 Case study: CED Research (University of California/National Cancer Institute
    • 6.2.2 Case study: Cintredekin besudotox (NeoPharm)
  • 6.3 Our opinion on minimally invasive delivery
• 7 Non-invasive delivery technologies
  • 7.1 Needle free delivery
    • 7.1.1 Case study: Intraject delivery (Zogenix Inc)
    • 7.1.2 Case study: Glide solid dose injector (Glide Pharma)
  • 7.2 Transdermal delivery
    • 7.2.1 Case study: PassPort system (Altea Therapeutics)
    • 7.2.2 Case study: Transdur patch (Durect / Endo Pharmaceuticals)
    • 7.2.3 Case study: Viaderm technology (Transpharma Medical)
    • 7.2.4 Case study: Exelon patch (Novartis)
    • 7.2.5 Case study: Antipsychotic patch (Dermatrends / Teikoku Pharma
    • 7.2.6 Case study: Zingo (Anesiva)
  • 7.3 Intranasal/pulmonary delivery
    • 7.3.1 Case study: Vianase - Controlled Particle Dispersion (Kurve Technology
    • 7.3.2 Case study: Tempo inhaler (MAP Pharmaceuticals)
    • 7.3.3 Case study: Intranasal midazolam (Intranasal Therapeutics
  • 7.4 Novel oral formulations
    • 7.4.1 Case study: Remoxy (Pain Therapeutics / King Pharmaceuticals)
    • 7.4.2 Case study: Spheromers (Spherics/Takeda)
    • 7.4.3 Case study: Oros implant (ALZA Corporation)
  • 7.5 Buccal melt
    • 7.5.1 Case study: Rapidmist (Generex)
    • 7.5.2 Case study: Sativex (GW Pharmaceutical)
  • 7.6 Reformulations
    • 7.6.1 Extended release
  • 7.7 Our opinion on non-invasive drug delivery technologies
• 8 Market trends in drug delivery in CNS
  • 8.1 Key drug delivery players in the CNS arena
  • 8.2 Recent partnerships and acquisitions
    • 8.2.1 Strategic partnerships & joint ventures
    • 8.2.2 Acquisitions
    • 8.2.3 Emerging specialty pharma companies
  • 8.3 Market trends now 2006-2012
    • 8.3.1 Global drug delivery market 2006-2012
    • 8.3.2 Pharma drivers and drug delivery trends by 201
  • 8.4 Market by 2020
    • 8.4.1 Pharma drivers and drug delivery trends by 2020
• 9 Summary & Conclusions
• 10 Bibliography
• 11 Acknowledgements
• List of Tables:
  • Figure 1.1: Schematic of the blood brain barrier
  • Figure 1.2: US$100 billion global CNS market 2006
  • Figure 1.3: Half a billion people affected with CNS conditions globally
  • Figure 1.4: Classes of CNS drugs approved
  • Figure 1.5: Drugs in clinical development for mental illness
  • Figure 4.1: CNS delivery opportunities
  • Figure 5.1: Mechanism of uptake of compacted DNA nanoparticles
  • Figure 5.2: Gene therapy for Parkinson's disease
  • Figure 5.3: ArmaGen's molecular Trojan horse
  • Figure 5.4: New approaches to Parkinson's disease
  • Figure 5.5: Sources of stem cells
  • Figure 5.6: Applications of stem cells
  • Figure 5.7: LipoBridge technology
  • Figure 5.8: Ablynx's nanobodies
  • Figure 5.9: Duros once-yearly osmotic implant
  • Figure 5.10: Duros system for delivery of antineoplastic agents into the brainstem for brain tumour
  • Figure 5.11: Sagittal CTS of Duros implant
  • Figure 5.12: Medtronic Mattric SCS sytem, percutaneous leads and laminotomy leads
  • Figure 5.13: Cyberkinetics brain gate implant
  • Figure 6.1: EKOS NeuroWaveTM Catheter in stroke
  • Figure 6.2: The NeuroWave catheter
  • Figure 6.3: Convection enhanced delivery image
  • Figure 6.4: CED imaging
  • Figure 6.5: Model of CED
  • Figure 7.1: Intraject delivery device
  • Figure 7.2: Application of interject device
  • Figure 7.3: Glide delivery technology
  • Figure 7.4: PassPort Delivery System - transdermal versus subcutaneous delivery of apomorphine in rats
  • Figure 7.5: Trasndur - transdermal patch
  • Figure 7.6: Viaderm transdermal delivery
  • Figure 7.7: Exelon patch
  • Figure 7.8: Dermatrend's A) transdermal technology and B) HRA molecule
  • Figure 7.9: Anesiva's Zingo
  • Figure 7.10: CPD delivery profile
  • Figure 7.11: Spherics drug delivery technologies
  • Figure 7.12: Oros drug delivery technologies
  • Figure 7.13: Rapidmist device
  • Figure 8.1: Total number of pharmaceutical and drug delivery deals (1997-2006
  • Figure 8.2: Drug delivery deals as a proportion of specialty pharma deals (2000-2007
  • Figure 8.3: Migration of CNS products from invasive to non-invasive delivery
  • Figure 8.4: CNS drug delivery landscape by 2020
• List of Tables
  • Table 1.1: Table drug expenditure in 2006
  • Table 1.2: Summary of key CNS drugs in clinical development - by therapeutic category
  • Table 3.1: Leading CNS delivery companies
  • Table 5.1: Medtronic's range of delivery technologies
  • Table 8.1: Summary of leading drug delivery companies and their delivery technologies
  • Table 8.2: Summary of recent alliances, agreements and acquisitions within CNS delivery
  • Table 8.3: Forecasts of approved CNS products 2006-2012 (US$ billion
  • Table 8.4: Forecasts of pipeline DD driven CNS products 2006-2012 (US$ million
  • Table 8.5: Leading CNS drug delivery specialist by 2020