Analysis of NIDCR’s Rare Disease PortfolioPreethi Chander, Jason Wan, Dolores Wells*

Division of Extramural Research & Office of Science Policy & Analysis*

National Institute of Dental and Craniofacial Research

What are “Rare” diseases?• Diseases which are characterized by a low prevalence (<200,000 people) in the

population. They frequently are associated with problems in diagnosis and treatment. • But, having a rare disease is not so rare. Of the roughly 6,800 rare diseases that are

known, about 10% of the US population has some form of rare disease. • There are more than 5,000 rare disorders that, taken together, affect approximately 20

million Americans. • One in every 12 individuals in this country has received a diagnosis of a rare disease

(from National Organization for Rare Disorders).

Data Sources for FY14 projects list• RePORT/RCDC- publicly reported “rare diseases” category • SCORE- NIDCR coding system, pre-defined disease subset• 121 overlap, 22 in RCDC alone, 113 in SCORE aloneConsolidated list of 256 unique projects used for the analysis SCORE coding allowed for additional grants to be included with those from RCDC “rare disease” category

NIDCR funding for rare diseases research has remained stable

$3,350

$3,400

$3,450

$3,500

$3,550

$3,600

$3,650

$-

$10

$20

$30

$40

$50

$60

2011 2012 2013 2014

Mill

ion

s

Mill

ion

s

NIDCR Amount excluding intramuralNIDCR Amount including intramuralNIH Amount including intramural

More than half the projects are related to head and neck cancer

AbstractIn order to understand the landscape of rare diseases affecting the dental, oral, and craniofacialskeleton, an analysis was conducted of NIDCR’s research grants in FY14. Using manually codeddescriptors of NIDCR’s funded research based on reading the applications abstracts, a broadcategorization was conducted. The aim was to gain an understanding of the current portfolio withregard to the disease research, and to explore needs, gaps, and opportunities in this area. Usinganalytical tools, additional examination of the research outputs, key players, and the impacts of theseoutputs are presented. By identifying the hurdles, successes, and state of progress towards clinicalreadiness in rare diseases, the NIH will be better poised to leverage resources for funding rare diseaseresearch in the area of dental, oral, and craniofacial science. The ultimate goal is to look at scientificareas where rare disease research has helped advance knowledge in related, but more common,diseases and pathways.

Publications • 559 from Jan 2014 to presentAdditional or continued funding of work• 85 competing renewals• 170 ongoing projectsPatents/Inventions/Therapeutics• No records in iEdison and ExPORTER• iREPORT showed that success stories were

mostly in basic sciences Publications resulting from FY14 list of grants from 2014-July 2015

Major themes from research publications

Summary• Funded research is heavy in basic sciences, with few pre-clinical studies. • There are no clinical trials in NIDCR portfolio.• More than half the projects are related to head and neck cancer.

Future Analyses• Are there other rare disease areas we should be funding?• What are the hurdles in advancing rare disease research?• Has rare disease research helped advance discoveries or treatment of more prevalent diseases?

Nat Med 2014 reports Asfotase alpha can

correct neurofibromatosis type-

1 skeletal dysplasia

1948 – Dr. Rathbun describes case of “Hypophosphatasia” (HPP)

Late 1990’s – NIDCR funds work on pathogenesis of HPP (Dr. Millan)

~2007 –Enobia Pharma & Dr. Millan begin work on HPP and ERT

2008 – Bone-targeted ALKP (ENB-0040) awarded Orphan Drug Designation

2010 – Phase II Clinical Trials completed

Decreased cortical porosity

HPP mouse model developed

Results published in 2012 show enhanced bone formation

NEJM

Enzyme Replacement Therapy (ERT) prevents Skeletal and Dental Defects

2013 – FDA grants Breakthrough Therapy designation for Asfotase alfa

2015 – Japan is 1st country to approve Asfotase alfa for treatment of HPP

The Hypophosphatasia StoryAsfotase alfa as an enzyme

replacement therapy

(iClean beta from OPA & Sci2)

Funded investigators collaborate on rare disease

projects

5%

46%

21%

1%

17%

9%

Clinical

Integrative &Infectious

Genomics

Behavioral

Training

unassignedBased on program codes which approximates

unique topic areas

Funded research is heavy in basic sciences, with few pre-clinical studies

Translational Pipeline

Clinical Trials 0

Human Subjects 41

Animal + Human subjects 49

Animal studies 117

In vitro 18

MechanismProject count

Research Project Grant 163

Fellowship 23

Career Development 18

Program Project 17

Intramural 14

Cooperative Agreement 13

NIH Director’s Award 6

Grand Total 254

97

28

126

0

20

40

60

80

100

120

Pediatric HIV Nutrition Sexvariable

Rare disease research in major policy areas

122

40

18

15

116 6 1 1

1

Number of unique projects from SCORE coding

A: Cancer Head & Neck

B: Clefts, Lip & Palate

C: Craniosynostosis

Amelogenesis/DentinogenesisImperfectaD: Craniofacial Multi-systemsyndromesE: Bone + Ligamentdisease/syndromesF: Other Diseases & Syndromes

A: Cancer Head & Neck, B: Clefts,Lip & PalateB: Clefts, Lip & Palate, C:CraniosynostosisAI and DI, B: Clefts, Lip & Palate

Disease overlap projects

Disease categorization by ORDR framework

Disease categories from Genetic and Rare Diseases Information Center (GARD)

-100 -80 -60 -40 -20 0 20 40 60 80 100

(Hereditary) Cancer (Syndromes)

Congenital and Genetic (Diseases)

Musculoskeletal (Diseases)

Digestive (Diseases)

Connective tissue (Diseases)

Immune System (Diseases)

Behavioral (and mental disorders)

Nutritional (Diseases)

Endocrine (Diseases)

Lung (Diseases)

(Male) Reproductive (Diseases)

Heart (Diseases)

Kidney and Urinary (Diseases)

Count in RCDC Concept Count in RCDC Categories