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General Session: Federal Response to the Rx Drug Abuse Epidemic - Dr. Francis Collins

General Session: Federal Response to the Rx Drug Abuse Epidemic - Dr. Francis Collins

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  • 1. Advancing Pain Relief, Preventing Abuse Francis S. Collins, M.D., Ph.D. Director, National Institutes of Health National Rx Drug Abuse Summit April 22, 2014
  • 2. “Science in pursuit of fundamental knowledge about the nature and behavior of living systems and the application of that knowledge to extend healthy life and reduce illness and disability.” ... NIH: Steward of Medical and Behavioral Research for the Nation
  • 3. NIH: Advancing Pain Relief; Preventing Abuse of Pain Relievers   NIH supports wide array of programs and projects that –  Enhance our understanding and treatment of pain –  Improve our ability to monitor and prevent abuse of pain relievers   Examples include: –  NIH Pain Consortium –  “Monitoring the Future” study –  Supporting research to curb epidemic of opioid abuse
  • 4. NIH Pain Consortium Centers of Excellence in Pain Education 12 CoEPEs in 9 states, >100 schools
  • 5. “Monitoring the Future”   Survey measures drug, alcohol, and cigarette use and related attitudes among adolescent students nationwide –  Started in 1975 –  Conducted at the University of Michigan –  Supported by NIH’s National Institute on Drug Abuse (NIDA)   2013 survey included 41,675 students from 389 public and private schools
  • 6. Percent of Students Reporting Nonmedical Use of Vicodin in Past Year, by Grade 0 5 10 15 20 02 03 04 05 06 07 08 09 10 11 12 13 8th Grade 10th Grade 12th Grade SOURCE: University of Michigan, 2013 Monitoring the Future Study *Denotes significant difference between 2012 and 2013 * Year
  • 7. Percent of Students Reporting Nonmedical Use of OxyContin in Past Year, by Grade 0 5 10 15 20 02 03 04 05 06 07 08 09 10 11 12 13 8th Grade 10th Grade 12th Grade SOURCE: University of Michigan, 2013 Monitoring the Future Study Year
  • 8. Research: Finding New Responses to Opioid Abuse   Develop abuse-resistant drug formulations   Devise user-friendly methods of antidote (naloxone) administration   Create mHealth interventions to help prevent opiate overdose   Produce new immunotherapies to treat addiction
  • 9. Abuse-Resistant Drug Formulations: Prodrugs   Problem: changing method of taking opioids – i.e., crushing, injecting – increases euphoria; abuse   Challenge: develop drugs that resist tampering; abuse   Research response: oxycodone prodrug –  Prodrugs: inactive compounds metabolized in the body to produce active drug –  NIH-supported Signature Therapeutics’ Bio-MD™ opioid prodrug •  Resists extraction, tampering •  2 prodrug types, for: -  Hydromorphone -  Oxycodone: priority
  • 10. Abuse-Resistant Drug Formulations: Oxycodone Prodrug   Two-step activation process in the body –  Taken orally, bioactivation by trypsin in GI tract –  Cyclization release reaction   Without activation, very little active opioid released   NIH support: –  NIDA –  National Center for Advancing Translational Sciences’ “Bridging Interventional Development Gaps” (BrIDGs) program •  Supports application to FDA
  • 11. User-Friendly Antidote Administration: Naloxone   Opioid overdose antidote: naloxone –  Effective: reversed >10,000 overdose cases, 1996–2010* –  Until recently, only available in injectable formulation •  Practically, limited use to emergency medical personnel   New formulation, Evzio, approved April 3, 2014 –  Hand-held auto-injector quickly delivers single dose –  Facilitates use by family members, caregivers   Simpler systems could expand availability even further –  NIH/NIDA supporting development of intranasal delivery systems *Centers for Disease Control and Prevention
  • 12. User-Friendly Antidote Administration: NIH-Supported Naloxone Nasal Sprays AntiOp   Developing single-dose, disposable nasal spray –  Combines proven nasal spray device with stable, concentrated, specially-formulated naloxone solution –  Investigational New Drug (IND) application filed with FDA in 2012 –  Could be on the market ~18 months Lightlake Therapeutics   Conducting clinical trials with intranasal naloxone for treatment of binge eating disorder –  Applying technology to treatment of opioid overdose –  Clinical trials began last fall
  • 13. mHealth Interventions May Help Prevent Opiate Overdose Wireless Sensors •  Respiration •  Oximeter •  Arrhythmias Naloxone Delivery •  Automatic •  Patient •  Third party Alarm •  Set up delivery •  Alert patient •  Alert third party
  • 14. A Shift from Abuse of Prescription Pain Relievers to Heroin Cicero TJ et al. N Engl J Med 2012;367:187-189. A recent increase in heroin use accompanied a downward trend in OxyContin abuse – following introduction of an abuse-deterrent formulation of OxyContin.
  • 15. Antibodies reduce amount of drug in the brain Capillary Blood Flow Brain Immunotherapies to Treat Addiction: Vaccines Targets drugs, not receptors Capillary Blood Flow Brain Antibodies Vaccine Binding sites
  • 16.   Vaccines using immune molecules to diminish effects of abused drugs have been developed   Heroin vaccine development trickier –  Heroin is metabolized into many substances – each with psychoactive effects   NIH-supported researchers used dynamic approach to develop heroin vaccine –  Targets not only heroin, but chemicals into which it degrades   Recent tests promising   George Koob, co-PI, now at NIH…. Immunotherapies to Treat Addiction: Heroin Vaccine
  • 17. Learning the Language of the Brain New Insights on the Horizon? “The Next Great American Project”
  • 18. BRAIN Buzz 2014
  • 19. 2013 Monitoring the Future Study Prevalence of Past Year Drug Use Among 12th graders Drug Prev. Drug Prev. Alcohol 62.0 Sedatives* 4.8 Marijuana/Hashish 36.4 Tranquilizers* 4.6 Hookah 21.4 Hallucinogens 4.5 Small cigars 20.4 MDMA (Ecstasy) 4.0 Amphetamines* 8.7 Hall other than LSD 3.7 Synthetic Marijuana 7.9 OxyContin* 3.6 Snus 7.7 Salvia 3.4 Adderall* 7.4 Cocaine (any form) 2.6 Narcotics o/t Heroin* 7.1 Inhalants 2.5 Vicodin* 5.3 Ritalin* 2.3 Cough Medicine* 5.0 LSD 2.2 * Nonmedical use Categories not mutually exclusive
  • 20. Percent of Students Reporting Use of Heroin in Past Year, by Grade 0 5 10 15 20 95 96 97 98 99 00 01 02 03 04 05 06 07 08 09 10 11 12 13 8th Grade 10th Grade 12th Grade Year SOURCE: University of Michigan, 2013 Monitoring the Future Study
  • 21. Percent of High School Seniors Reporting Use of Narcotics Other than Heroin 0 5 10 15 20 91 92 93 94 95 96 97 98 99 00 01 02 03 04 05 06 07 08 09 10 11 12 12th grade SOURCE: University of Michigan, 2013 Monitoring the Future Study Year
  • 22. Percent Reporting Narcotics Other Than Heroin as ‘fairly easy’ or ‘very easy’ to Obtain, by Grade 0 20 40 60 80 100 92 93 94 95 96 97 98 99 00 01 02 03 04 05 06 07 08 09 10 11 12 13 8th Grade 10th Grade 12th Grade SOURCE: University of Michigan, 2013 Monitoring the Future Study *Denotes significant difference between 2012 and 2013 *
  • 23. •  Collaborator: Signature Therapeutics (Palo Alto, CA) •  Compound: Oral prodrug formulation of oxycodone   Tamper-resistant - Common methods of tampering do not release appreciable amounts of the active opioid. •  Novel Project Intake Model   MOU between NIDA and NCATS   3-way CRADA including Signature •  Pending BrIDGs Studies:   GMP synthesis   Packaging of drug supply   PK/ADME and GLP toxicology studies •  IND Goal: End of 2014
  • 24. Binding Site Capillary Blood Flow Brain Antibodies VACCINE Antibodies Can Reduce Brain Concentrations Immunotherapies for Addiction Treatment (i.e., Vaccines) Capillary Blood Flow Brain Targeting the drugs, not the receptors
  • 25. ##p<0.01, ###p<0.001, significant reduction of analgesia vs. Control/KLH group, ### p<0.001, significant reduction of analgesia vs. Control/KLH group Heroin  1  mg/kg,    s.c.   30  min   Hot Plate Test The Vaccine(s) Immunotherapies to Treat Addiction: Heroin Vaccines *K.D. Janda & G.F. Koob Laboratories at TSRI Dr. Koob now at NIH