W. Keith Hoots MDDirector, Division of Blood Diseases and

Resources

National Heart, Lung, and Blood Institute

Sickle Cell Disease Stakeholder’s Meeting

June 25th and 26th, 2015

SCD Research at NHLBI: Strategies for the Near-term Future

Items for Discussion

o Implementation Science Research: Investigating strategies to extend proven treatments to sickle cell populations that have not had optimal access to them

o Global Sickle Cell Disease: An effort to enhance SCD research infrastructure in Sub-Saharan Africa

o Developing New Drugs/Therapies for SCD: Opportunities for public-private partnerships

o SCD Outreach: Challenge awards for undergraduate teams

(Expert Opin. Emerging Drugs (2015) 20(1):47-61)

CompoundStage of Development

Mechanism of Action

NHLBI Developmental Support

DecitabineAstex Pharmaceuticals

Active, Phase II Study for SCD

DNA Methylase Inhibitor, Hb F Induction

1 R01 HL073432-011 U54 HL090513-011 R41 HL110727-012 U10 HL069278-111 U01 HL117658-01

GMI-1070GlycoMimetics

Active, Phase II Study for SCD

Inhibits Cellular Adhesion

1 U54 HL070585-011 R01 HL111969-011 R01 HL094400-011 RC1 HL099545-012 R44 HL093893-03

SelG1Selexys Pharmaceuticals

Active, Phase II Study for SCD

Inhibits Cellular Adhesion

1 RC1 HL099545-012 R44 HL093893-031 U54 HL070585-01

RegadenosonGilead Sciences

Active, Phase II Study for SCD

Anti-inflammatory Agent

1 R34 HL108757-011 P50 HL110790-011 R01 HL111969-01

TiclopidineKRKA

Widely Launched, Phase III Study Recruiting for Pediatric Patients with SCD

Anti-inflammatory Agent

1 R01 HL060683-012 R01 HL055646-054 R37 HL030657-181 R43 HL071433-011 R44 HL079701-011 K01 HL092586-01

Purified Polaxamer 188CytRx

Active, Phase II Study Complete

Reduces Viscosity None

NHLBI Contributions to Drug Development

(Expert Opin. Emerging Drugs (2015) 20(1):47-61)

CompoundStage of Development

Mechanism of Action

NHLBI Developmental Support

Nitric OxideIkaria

Active, Phase III Study for SCD

Vasodilator 1 U54 HL090513-011 Z01 CL001173-01

PF 04447943Pfizer

Active, Phase I for Patients with SCD

Selective PDE 9 Inhibitor

None

NKTT120NKT Therapeutics

Active, Phase I for Patients with SCD

Reduces Chronic Inflammation Associated with SCD

1 R43 HL123127-01

AES-103Baxter International

Active, Phase I Completed for SCD. Phase II in Process of Recruitment

Anti-Sickling Agent 1 R01 HL121386-01A1

NHLBI Contributions to Drug Development

Multi-disciplinary undergraduate teams design an educational strategy about SCD to their community

Cash prize to the winning, second place and third place entries based on creativity and content

Each of the above groups will be invited to Bethesda to demonstrate their educational intervention at NHLBI

Target: Fall Semester 2015

Challenge Competition Funding Opportunity Announcement for Undergraduates

What is Implementation (T4) Science?

Why is it needed to address the needs of the US SCD population?

How does NHLBI propose to use this research approach to meet SCD patient needs?

Implementation Science Research: Investigating Strategies to Extend Proven Treatments to SCD Populations that have not had

optimal access to them

T4 research seeks to study, in a scientifically rigorous way, the best methods to reach the “real world”, including clinicians, patients, healthcare systems, and populations to ensure that prevention and treatments are delivered with high fidelity and sustained long-term.

T4 Research Definition

Why initiate a global research effort in Sub-Saharan Africa?

Who will be enlisted to participate?

What NHLBI support will be provided to launch this research effort?

Who will partner with us in this endeavor?

Global Sickle Cell Disease: An NHLBI Effort to Enhance Research Infrastructure in Sub-Saharan Africa

What potential new drugs are in development for SCD and what is the probability that any will be licensed?

How has NHLBI supported the science that has enabled pharmaceutical companies to undertake such development after a long period of time when Hydroxyurea has been the only licensed drug for SCD?

Why does a diverse drug development portfolio make sense for SCD, especially since the only curative regimen (bone marrow or blood cell transplantation) has been available to so few patients?

Are there reasonable possibilities that SCD can be cured? If so, for whom?

Developing New Drugs/Therapies for SCD: Opportunities for Public-Private Partnerships

Harvey Luksenburg and Keith Hoots on Behalf of the NHLBI Sickle Cell Disease Implementation Research Team and our

NIMHD, HRSA and Other Federal and Private Partners

A Research Effort Designed to Positively Impact the Health of Adolescents and Adults with SCD in the USA

Example of Barriers to Care: Fragmentation of Health Care for SCD

• Many patients are not followed in clinics, and only use ERs

• After hospitalizations, poor follow-up post-discharge

• Difficulty in accessing primary care and specialty care (hematologists)

• Problems with transportation, child care, school attendance, work-related issues

• Lack of insurance/knowledge of eligibility

Creating a Consortium from a “Neighborhood” of SCD Patients and Providers: A Requisite for this Implementation Research Initiative

• A Consortium will consist of a team of all providers (community,-based, acute care, and academic centers) that are responsible for the care of adolescents/adults with SCD in a geographic area defined by the investigative team and their collaborators

• Institutions comprising a consortium must collectively enroll at least 300 adolescents/adults (age 15-45)with SCD for prospective longitudinal follow up and enrollment in an implementation research project developed by the team in collaboration with NIH

Norma B. Lerner MD, MPH and W. Keith Hoots MD

National Heart, Lung, and Blood Institute

The Sickle Cell Disease in Sub-Saharan Africa Initiative

(Lancet 13; 381: 142-151)

Global Burden 2010

An estimated 312,000 neonates

born with Hb SS disease

Just under 5.5 million were born with S trait

Data does not reflect:- Incidence of compound disorders (Hb SC, SE,

Sβ thalassemia)- Numbers of all-age affected individuals- Disability levels

SCD – Background on the World-wide Incidence

(Lancet 13; 381: 142-151)

Africa

AmericasU.S.

Nigeria

DR Congo

TanzaniaUganda

Hb SS births/yr.

SCD Incidence: Africa versus the Americas

Objective:

To help establish a sustainable Sickle Cell Disease Investigative Network in Sub-Saharan Africa

Such a network would advance future SCD related epidemiologic, clinical, & implementation research to the benefit of SCD patients world wide

A Capacity Building NHLBI Initiative: SCD in Sub-Saharan Africa (SSA)

A Collaborative African SCD Consortium

An African based Data Coordinating Center

Training programs led by partnering regional groups and U.S. agencies & societies

NHLBI Initiative: SCD in SSAProposed Program Structure

“15-20% of adult patients were being treated with hydroxyurea in the most recent 3 month period”: Journal of the American Medical Association, April 28, 2015, vol 313, no. 16.

A diverse health system where access to care is not universal and entry is often through emergency centers

Patients with SCD in the US (particularly adults) often do not appear to access optimal treatment*

Why Fund Implementation Science Research in SCD in the U.S.