CTSA PROGRAM STEERING COMMITTEE [OPEN SESSION]

JULY 10, 2017 2:30 – 4:00 ET

Agenda

2

2:30 Welcome Kathleen Brady

Redonna Chandler

2:35 – 3:30 NIH Opioid Crisis Presentation and

Discussion

Chris Austin (NCATS Director)

Nora Volkov (NIDA Director)

3:30 - 4:00 NCATS CTSA Program Policy and Procedure

for Surveys

Governance for the Clinical and

Translational Science Awards (CTSA) Program

Erica Rosemond

Discussion by SC Members

NIH’s Efforts to Reduce the Opioid Epidemic

Nora D. Volkow, M.D.Director

@NIDAnews

National Instituteon Drug Abuse

Numbers in Millions

Source: SAMHSA, 2015 National Survey on Drug Use and Health, 2016.

Current Drug Use Rates in Persons Ages 12+

Past Year Nonmedical Use of Psychotherapeutic Drugs

Persons Ages 12+

0.3

0.5

1.2

1.9

6.4

22.2

27.1

0 10 20 30

Heroin

Inhalants

Hallucinogens

Cocaine

Psychotherapeutics

Marijuana

Any Illicit Drug

Prescription Drug Misuse/Abuse is a Major Problem in the US

4.74.9

5.1 54.84.94.8

4.3

4.8

4.2

3.9

4.7

2.12.22.12.1 22.22.2

22.3

2 2 2.3

1.21.11.4

1.21.11.21.1 11.31.31.4

2

0.30.30.40.30.20.30.40.20.20.20.30.6

0

1

2

3

4

5

6

Trendline break due to questionnaire change in 2015

Overdose Death Rates

Designed by L. Rossen, B. Bastian & Y. Chong. SOURCE: CDC/NCHS, National Vital Statistics System

1999 2015

2015 Overdose Deaths:

52,404 Any Drug

33,091 Any Opioid

Opioid OD Deaths US, 2000-2015

266 260 253242 234

222

0

50

100

150

200

250

300

201020112012201320142015

OP

IOID

MM

E IN

BIL

LIO

NS

Source: IMS Health, U.S. Outpatient Retail Setting

Opioid morphine milligram

equivalents (MME) dispensed fell by over 15% from 2010-2015

Opioid Prescriptions have started to Decrease

but Opioids Fatalities are still Increasing

Heroin Price Has Decreasedin Recent Years

$-

$500

$1,000

$1,500

$2,000

$2,500

$3,000

$3,500

"Retail" Price Per PureGram

National Drug Control Strategy--Data Supplement 2014. https://www.whitehouse.gov/sites/default/files/ondcp/policy-and-research/ndcs_data_supplement_2 014.pdf

Emerging Illicit Synthetic Opioids

• Increasing reports of fentanyl laced-heroin

and prescription pills

• Other synthetic opioids emerging i.e.,

Carfentanil

PAIN MANAGEMENT

Safe, more effective strategies

OPIOID ADDICTION

TREATMENT

New and innovative

medications and

technologies

OVERDOSE REVERSAL

Interventions to reduce

mortality and link to

treatment

Using Research to End the Opioid Crisis

NIH OPIOID RESEARCH INITIATIVE

Safe, More Effective Strategies for Pain Management

Non-pharmacological treatmentNeural stimulation;

Surgical interventions; Meditation

Non-Opioid AnalgesicsCannabinoids;Inflammatory mediators; Ion channel blockers

Targeted Opioid Analgesics

with reduced potential for addiction and overdose

Biologics

e.g. antibodies that bind to pain producing cytokines

Soergel DG et al., Pain 2014; 155(9):1829–1835.

Biased Mu-Opioid Receptor Ligands:

New Generation Of Pain Therapeutics

Knowledge of Pain Pathways –

New Biomarkers for Pain?New study assess glial role in human pain

• Patients with low back pain (LBP) versus controls

– Uses PET to detect levels of glial protein (TSPO)

– Demonstrates role of glial activation in human pain

– Possible biomarker

– May suggest new treatments for chronic pain

Loggia et al., Brain 2015;138.

Limiting Abuse by Predicting Addiction

• OPRM1 encodes for the target of

opioids

• Can variants predict likelihood

addiction?

• OPRM1 variant

– Affects receptor levels in brain

– Associated with increased risk

for addiction, overdose severity

Hancock et al., Biol Psychiatry 2015; 78.

Manini et al., J Med Toxicol 2013; 9.

Peciña et al., Neuropsychopharmacology 2015; 40.

Variant Common Type

Mapping the differences

Intravenous

User Friendly Naloxone

NARCAN® Nasal Spray device-- $37.50 per 4mgApproved by FDA November 2015

2,000

4,000

6,000

8,000

10,000

12,000

14,000

02/16 05/16 08/16 11/16 02/17

IMS

Mo

nth

ly P

resc

ript

ions

Narcan Nasal Spray All other naloxone products

• Naloxone Px increased 3.5X in past year

• NARCAN® Nasal Spray is the most prescribed

naloxone

• 900,000 NARCAN® Nasal Spray doses

distributed since launch in 2/16

Opioid Overdose Reversal

By tNarcan® Nasal Spray

N=245

Avetian GE et al., Current Medial Research and Opinion, 23 May 2017.

Overdose Treatment: Saving

Lives for Future Recovery

• New stronger, longer acting

formulations to address more

potent opioids (e.g. fentanyl)

• Stimulation devices to prevent

respiratory depression

• Overdose detection and alert

technologies

• Post-overdose interventions to

ensure engagement in treatment

Medications Assisted Therapies for OUD

effect

no effect

agonist antagonist

Op

ioid

Eff

ec

t

Full Agonist(Methadone: Daily Dosing)

Partial Agonist(Buprenorphine: 3-4X week)

Antagonist(Naltrexone: ER 1 month)

Log Dose

DECREASES:

• Opioid use

• Opioid-related OD deaths

• Criminal activity

• Infectious disease

transmission

And INCREASES

• Social functioning

• Retention in treatment

• Outcomes in NAS

MAT is highly underutilized

Sigmon SC et al. N Engl J Med 2016.

Abstinence from Illicit Opioids over 12 Weeks with

Interim Buprenorphine

5.4 5.4 5.6

0.9

2.3 2.4

0

1

2

3

4

5

6

Buprenorphine Referral Brief Intervention

Baseline 30 days

Emergency Department-Initiated

Buprenorphine – Reduced self-reported, illicit opioid use

– Increased engagement in addiction

treatment

– Decreased use of inpatient addiction

treatment services

Da

ys

Self-Reported Illicit Opioid Use in the Past 7 Days

D’Onofrio G et al., JAMA April 28, 2015.

Overdoses in 78 weeks:

Control: 7

Naltrexone: 0

Naltrexone Trial in CJ Populations

• Participants: parolees/probationers with opioid addiction – all

volunteers – received either

– Monthly injections of extended release naltrexone for 6 months

– Community treatment, including methadone or Suboxone

(encouraged)

O’Brien et al., Poster presentation at the Annual Meeting of the College on Problems of Drug Dependence, June 2015.

Relapse Frequency

Pro

ba

bilit

y o

f No

Rel

apse

Weeks

Treatment as usual

Naltrexone

Lee et al. NEJM March 31, 2016.

Improving Treatments for Addiction:

Rosenthal et al., Addiction 2013;105.

PROBUPHINE®

FDA approval – May 26, 2016

Extended Release Formulations

Vivitrol®

Krupitzky et al., Lancet 2011

Placebo: N=124

XR-NTX: N=126

IM Injection q 4 weeks for 24 weeks

Median % Opioid-Negative Urines

Pe

rce

nt

of W

ee

kly

Uri

ne

Te

sts

100%

80%

60%

40%

20%

0%

PLACEBO XR-NTX

Innovative Opioid Addiction Treatments:

Fentanyl Vaccine • 2016: First vaccine for fentanyl and fentanyl

analogs reported in a mouse model

• Successfully stimulated antibody production

• Reduced fentanyl reaching the brain

• Reduced analgesia and protected against overdose

Bremer et al, 2016;

Janda and Treweek, 2012.

Cutting Edge Science Meeting Series

to End the Opioid Crisis

Medications Development for Opioid Use Disorders and

for Overdose Prevention and Reversal -- June 5, 20171

Development of Safe, Effective, Non-Addictive

Pain Treatments -- June 16, 2017 2

3 Understanding the Neurobiological Mechanisms

of Pain -- July 7, 2017

CTSA’s Potential Role

ED Network

• Testing new MAT ER formulations in OD patients with OUD

• Epidemiological studies to characterize OD patients (ie., pain patients vs OUD patients;

symptomatology, doses of naloxone required, rate of response).

• Implementation research for after care models for treatment of OUD

Primary Care Physicians Network• Implementation research for initiation and follow up of ER MAT formulations

• Clinical trials for testing new analgesics or other pain therapeutics

• Research on development of biomarkers for pain with predictive clinical validity

Neonatal Unit Network• Implementation research for models of after care for mothers with OUD

• Clinical research on treatment of NAS

PAIN

ORWH

OBSSRNIDA

NIDCR

NINDS

NIA

NINRNICHD

NIAMS

NCCIH

NIH Pain Consortium Centers of Excellence in Pain Education

Goal: Improve pain treatment through education

Education

SUD

Goal: Prevent SUD and improve outcomes in addiction through education of health care providers

SCIENTIFIC STRATEGIES FOR COMBATING THE OPIOID EPIDEMICSHORT-TERM STRATEGIES INTERMEDIATE STRATEGIES LONG-TERM STRATEGIES

TREATMENT

OF OPIOID-USE

DISORDERS

TREATMENT

OF CHRONIC PAIN

New formulations of existing medications

Repurposing approved therapies (e.g., lorcaserin)

Novel medications targeting neurobiology (e.g., lofexidine)

*Vaccines and monoclonal antibodies

Brain-stimulation technologies

Opioid formulations with abuse-deterrent properties

M OR-biased agonists

Cannabinoids

Novel or repurposed medications targeting pathophysiology (e.g., sodium-channel blockers)

M onoclonal antibodies

Brain-stimulation technologies

*Gene therapies

*Progenitor cell therapies

Precision medicine

BiomarkersAdapted from Volkow & Collins,

NEJM , 2017.

OVERDOSE

PREVENTION

& REVERSAL

Stronger opioid antagonist formulations

Novel medications (e.g., 5-HT1A agonists, ampakines)

Phrenic-nerve stimulation devices

Technologies to detect overdose & alert help or autoinject naloxone

ERICA ROSEMOND, PHD, PROGRAM DIRECTOR

SAM JONSON, M.P.S, OPERATIONS MANAGER

DIVISION OF CLINICAL INNOVATION

NATIONAL CENTER FOR ADVANCING TRANSLATIONAL SCIENCES

STEERING COMMITTEE MEETING 7.10.2017

Governance and Surveys

for the CTSA Program

24

Governance for the CTSA Program

Surveys

25

Surveys are generated from different groups and/or sources and will be processed in different ways:

A. DTF Survey - generated from one or more DTFs or their working groups▪ Within DTFs: Approvals and distribution managed within and across DTFs

▪ External to DTFs: SC and DCI leadership reviews

B. CTSA Program Grantee Survey - generated from NCATS-funded grants (e.g. TIN, CCIAs, admin supplement, coordinating center) ▪ If peer reviewed already: SC informed for feedback

▪ If not peer reviewed: SC and DCI leadership reviews

C. CTSA Program Partner Survey - generated from a hub and/or an affiliated partner institution▪ SC and DCI leadership reviews

D. External Survey - generated by a group not affiliated(is external to the CTSA Program) ▪ DCI leadership reviews and SC reviews

REQUESTING FEEDBACK BY COB AUGUST 11 TO:ERICA.ROSEMOND@NIH.GOV

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