Prevalence of Hepatitis Delta Virus Infection in the United States

June 28th, 2017 12:00 PDT/ 3:00 EDT

Eduardo B. Martins, M.D., D.Phil.

SVP, Liver and Infectious Diseases

Eiger Biopharmaceuticals

6/30/2017 2

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PREVALENCE OF HEPATITIS DELTA VIRUS INFECTION IN THE UNITED

STATES

Eduardo B. Martins, M.D., D.Phil. SVP, Liver and Infectious Diseases

Eiger Biopharmaceuticals

June 28, 2017

6/30/2017 5

Disclosures

• Eiger Biopharmaceuticals

– Employee

– Shareholder

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Outline

• Chronic Hepatitis Delta (HDV) background – HDV infection

– Global prevalence

– US data

• US Prevalence study – Methods

– Results

– Limitations

– Conclusions

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Hepatitis Delta Virus The Most Severe Form of Chronic Viral Hepatitis

• HDV leads to the most severe form of viral

hepatitis

– More rapid progression to liver cirrhosis

– 5-7x more likely to develop cirrhosis and vs HBV

• HDV is always associated with HBV Infection

– Defective virus that needs HBsAg for propagation

• No FDA approved Rx for HDV

– PEG IFN α demonstrates modest benefit

• HDV worldwide prevalence is 15 - 20 million

– Approximately 4-6% of HBV population is infected with HDV

– Orphan disease in US and EU

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HDV Global Prevalence: 15-20 Million 4-6% of HBV-Infected Population Infected with HDV

HDV Worldwide Prevalence: 15 - 20 Million 6% of HBV Population Infected with HDV

9 (Range 0 - > 60%)

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Migration and Viral Hepatitis Globalization of Disease

Migration and Viral Hepatitis Globalization of Disease

Foreign-born individuals

comprise majority of growing

HDV positive population in

North America and

Western Europe…

Germany: Wedemeyer et al., Hepatology 2007

Heidrich et al., J Viral Hepatitis 2009

France: Le Gal et al., Hepatology 2007

UK: Cross et al., J Med Virol 2008

Italy: Stroffolini et al., J Med Virol 2009 Piccolo et al., Eur J Publ Health 2010

10

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118K

51K

36K 25K 22K

15K

33K

13K 9K 7K 6K 4K

0 K

25 K

50 K

75 K

100 K

125 K

150 K

Nu

mb

er

of

Pati

en

ts

Prevalence of HDV by Geography

HDV, True Prevalence

US Italy Germany France UK Spain

Estimated HBV Prevalence 2 M 600 K 328 K 496 K 256 K 212 K

Estimated Dx HBV Prevalence 553 K 148 K 81 K 132 K 67 K 52 K

Percent of HBV

Co-infected with HDV 5.9% 8.5% 11% 5% 8.6% 7.1%

Estimate for Total HDV Patient

Pool 118 K 51 K 36 K 25 K 22 K 15 K

Estimate for Dx HDV Patients 33 K 13 K 9 K 7 K 6 K 4 K

Estimates of HDV Prevalence in the US and EU-5 Ranges Vary From 15K-118K

Slide courtesy of Dr. Robert Gish

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HBV in Foreign-Born Persons in the US

• Estimates of the prevalence of HBV in the United States differ significantly

• Systematic review of HBsAg seroprevalence rates in 102 countries – 256 seroprevalence surveys in emigrants from 52 countries (including 689,078

persons) – 1,797 surveys in the general populations of 98 countries (including 17,861,035

persons)

• Data combined using meta-analytic methods to determine country-specific HBV prevalence rates

• Rates calculated using the number of FB living in the United States in 2009 by country of birth

• 1.32 million (95% confidence interval: 1.04-1.61) FB in the United States with HBV – 58% migrated from Asia, 11% migrated from Africa, and 7% migrated from Central

America

Kowdley, K et al. Hepatology 2012; 56: 422-433.

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HDV in the US Veterans Administration

• Retrospective study of all veterans positive for HBsAg from Oct 1999 to Dec 2013

• 25,603 patients with positive HBsAg – 2175 (8.5%) were tested for HDV; 73 (3.4%) tested positive

• HDV testing associated with being tested for HBV, HIV, and HCV • Predictors of (+)ve HDV results

– Substance abuse and cirrhosis – Abnormal ALT with suppressed HBV DNA (OR 3.2, 95%CI 1.4–7.5)

• Incidence rates of HCC 2.9 fold higher in HDV (+)ve (p = 0.002) • HDV independently associated with HCC (OR 2.1, 95%CI 1.1–3.9)

Kushner, T et al. J Hepatol 2015; 63: 586-592.

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HDV in Northern California

• Retrospective chart review of all HBV patients at CPMC

• 1191 HBV patients – 499 had been tested for HDV

– 42 (8%) coinfected; half of these were also hepatitis C virus-infected

– Cirrhosis in 73% of HBV/HDV, 80% of HBV/HDV/HCV, 22% of HBV

– 29 patients (69%) Caucasian non-Hispanic

– 10 (24%) Asians and Pacific Islanders

Gish, R et al. J Gastoenterol Hepatol 2013; 28: 1521-1525.

PREVALENCE OF HEPATITIS DELTA VIRUS INFECTION IN THE UNITED STATES

Results from an ICD-10 Review

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Methods

• Analysis of International Classification of Diseases (ICD) 9 and 10 codes for patients with HDV/HBV coinfection data from two longitudinal patient databases

• Initial analysis using Truven MarketScan® – Database contains medical claims info for over 170 million de-identified

US patients • 2nd, more detailed analysis used SHS Integrated Universe’s PatientSourceTM

– Comprehensive longitudinal patient database with over 4 billion prescription, medical, and hospital claims linked to anonymous patient identifiers, practitioners and payers

– Claims’ information for over 274 million patients, accounting for over 73% of all prescriptions, over 58% of all electronically processed medical claims and 25% of all hospital claims

– The entire dataset is linked to each de-identified patient, with 75% of patients with a linked prescription and diagnosis claim

• To avoid counting a single patient multiple times only unique patient counts are included

Martins, E and Glenn, J. Prevalence of Hepatitis Delta Virus (HDV) Infection in the United States: Results from an ICD-10

Review. Poster Sa1486 DDW May 2017.

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ICD-9 and ICD-10 Codes for HBV and HDV

Martins, E and Glenn, J. Prevalence of Hepatitis Delta Virus (HDV) Infection in the United States: Results from an ICD-10 Review. Poster Sa1486 DDW May 2017.

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Growing Number of Newly Diagnosed HDV Patients* in the US

4,946 4,274

4,841 5,043 5,259

5,916 6,386

7,442

9,079

-

1,000

2,000

3,000

4,000

5,000

6,000

7,000

8,000

9,000

10,000

2008 2009 2010 2011 2012 2013 2014 2015 2016

* Unique Patients Martins, E and Glenn, J. Prevalence of Hepatitis Delta Virus (HDV) Infection in the United States: Results from an ICD-10 Review. Poster Sa1486 DDW May 2017.

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Newly-Diagnosed Chronic HBV Patients and % with HDV Incidence Appears Higher Than Previous Estimates

0.0%

2.0%

4.0%

6.0%

8.0%

10.0%

12.0%

14.0%

-

10,000

20,000

30,000

40,000

50,000

60,000

2008 2009 2010 2011 2012 2013 2014 2015 2016

% o

f C

hro

nic

HB

V P

ts w

ith

HD

V

Ne

wly

Dx

Ch

ron

ic H

BV

Pts

Newly Dx Chronic HBV Patients (Unique) % of Chronic HBV with HDV

Martins, E and Glenn, J. Prevalence of Hepatitis Delta Virus (HDV) Infection in the United States: Results from an ICD-10 Review. Poster Sa1486 DDW May 2017.

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% Chronic HBV Patients Tested for HDV Low Testing Rate May be Concealing True Prevalence

0.0%

0.5%

1.0%

1.5%

2.0%

2.5%

3.0%

3.5%

4.0%

4.5%

5.0%

-

500

1,000

1,500

2,000

2,500

3,000

3,500

4,000

4,500

2008 2009 2010 2011 2012 2013 2014 2015 2016

% C

hro

nic

HB

V T

est

ed

fo

r H

DV

HD

V T

est

s O

rde

red

# HDV Test Claims (CPT 86692) % Chronic HBV Tested for HDV

Martins, E and Glenn, J. Prevalence of Hepatitis Delta Virus (HDV) Infection in the United States: Results from an ICD-10 Review. Poster Sa1486 DDW May 2017.

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HDV Geographic Footprint is Growing

• 25% (15,631) of all HDV patients in the US reside in 5 three-digit zip codes (Brooklyn, NY, Chicago, IL, Bronx, NY, Corona, NY and Huntington Station, NY)

• The HDV population resident in the top 20 three digit codes comprise 43% (27,601) of all HDV patients in the US

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Top 20 US Geographies for HDV Patients

6.50%

5.69%

4.29% 4.24%

3.51%

2.72%

1.96%

1.46% 1.45% 1.29% 1.22% 1.22%

1.09% 1.04% 0.90% 0.89% 0.84% 0.84% 0.84% 0.81%

0.00%

1.00%

2.00%

3.00%

4.00%

5.00%

6.00%

7.00%

Martins, E and Glenn, J. Prevalence of Hepatitis Delta Virus (HDV) Infection in the United States: Results from an ICD-10 Review. Poster Sa1486 DDW May 2017.

6/30/2017 22

HDV Geographic Footprint is Growing

Consistently high areas of HDV patient concentration

Brooklyn, NY Bronx, NY Corona, NY

Scarsdale, NY Passaic, NJ Jamaica, NY

San Francisco, CA

Yonkers, NY Pittsburgh, CA

Huntington St, NY

Philadelphia, PA

New York, NY La Puente, CA

Specific areas that have recently become high concentration include:

Chicago, IL Berwyn, IL Oviedo, FL

Miami, FL Parkville, MD Gainesville, FL

Lombard, IL Orlando, FL Staten Island, NY

Waukegan, IL Hempstead, NY

Hialeah, FL

Based on inclusion in top 20 HDV patient geographies ≥4 times from 2008 to 2013

Based on inclusion in top 20 HDV geographies ≥2 times from 2013-2016. Cannot be included on top 20 list >3 times between 2008 and 2012

Martins, E and Glenn, J. Prevalence of Hepatitis Delta Virus (HDV) Infection in the United States: Results from an ICD-10 Review. Poster Sa1486 DDW May 2017.

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Comparison of HDV Patient Footprint 2008 vs 2016 Top 20 Geographies for Each Year

2008 2016

1. Brooklyn, NY 6. Bronx, NY 11. La Puente, CA 16. Chicago, IL

2. New York, NY 7. Philadelphia, PA

12. St. Petersburg, FL

17. Franklin, MA

3. Yonkers, NY 8. Jamaica, NY 13. Staten Island, NY

18. Las Vegas, NV

4. Corona, NY 9. San Francisco, CA

14. Pittsburg, CA 19. Newburgh, NY

5. Scarsdale, NY 10. Passaic, NJ 15. Detroit, MI 20. Huntington ST, NY

1. Chicago, IL 6. New York, NY 11. Huntington ST, NY

16. Cicero, IL

2. Berwyn, IL 7. Bronx, NY 12. Philadelphia, PA

17. Parkville, MD

3. Brooklyn, NY 8. Jamaica, NY 13. Houston, TX 18. Miami, FL

4. Corona, NY 9. Lombard, NY 14. Passaic, NJ 19. Hialeah, FL

5. Waukegan, IL 10. Aurora, IL 15. Staten Island, NY

20. Las Vegas, NV

Martins, E and Glenn, J. Prevalence of Hepatitis Delta Virus (HDV) Infection in the United States: Results from an ICD-10 Review. Poster Sa1486 DDW May 2017.

6/30/2017 24

Limitations of Our Study

• Databases mostly capture insured patients

• Ethnicity of identified patients is not captured in this study

• Given the high prevalence of HBV in foreign-born, it is conceivable that many HBV-infected patients are not captured in our data

• Antibody test may not correlate with HDV RNA by PCR

• Data may be skewed by disproportionate impact of tertiary centers

• Total anti-HDV test does not differentiate between ongoing and past infection

Martins, E and Glenn, J. Prevalence of Hepatitis Delta Virus (HDV) Infection in the United States: Results from an ICD-10 Review. Poster Sa1486 DDW May 2017.

6/30/2017 25

Conclusions

• More than 11.8% of patients with chronic HBV may be coinfected with HDV

• Only 4.7% of chronic HBV patients are tested for HDV coinfection • Even a small increase in HDV testing among chronic HBV patients

has yielded significant increases in the numbers of detected HDV/HBV coinfection cases in the US

• Given the propensity for HDV to cluster geographically, it is important for clinicians to be aware of the growing footprint associated with the HDV patient population and the potential for undiagnosed HDV cases

• These data support the need for increased HDV testing among chronic HBV patients. HDV testing is readily available through commercial laboratories in the US

Martins, E and Glenn, J. Prevalence of Hepatitis Delta Virus (HDV) Infection in the United States: Results from an ICD-10 Review. Poster Sa1486 DDW May 2017.

Thank you!

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Eduardo B. Martins, M.D., D.Phil.

SVP, Liver and Infectious Diseases

Eiger Biopharmaceuticals

6/30/2017 27

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Q & A

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