# Presentation: 834739

## Slides Presented During Q & A

## Expected Events in Untreated PatientsOver 5 Years

- a Taiwan Observational Cohort Study and Safety Cohort
- b Chen CJ et al. EASL 2005, abstract 1256c Iloeje UH. EASL 2005, abstract 1265

**Non-skin****Non-HCC cancers****a**

**HCC****b**

**Cirrhosis****c**

**Events / 1000 Patients**

**15-20**

## Pregnancies in ETV Clinical Program: Outcome (N = 41)

**Safety Update**

| Outcome | ETVN = 21 | LVDN = 16 | ETV / LVDN = 2 | PlaceboN = 2 |
| --- | --- | --- | --- | --- |
| Elective Termination | 13 | 12 | 0 | 1 |
| Spontaneous Abortion | 1 | 3 | 0 | 1 |
| Live Birth | 3 | 1 | 2 | 0 |
| Outcome Unknown | 4 | 0 | 0 | 0 |

**5-79**

## Substitutions Selected by ETV

| Study | Patient Population | Residues with Novel Emerging Substitutions | ETV EC50 |
| --- | --- | --- | --- |
| 022 | Nucleoside naïve, eAg+ | E8G, E8Q, R18K, V23A, N33S, G52R, S57P, A62T, S75P, N76K, S78T, R110G, N118S, R120K, H124Q, L132R, L147P, Y148H, G152E, K154R, K154T, H156Y, R167Q, P170S, F178S, A181T, I187V, K212R, K212T, S219P, T222S, L229S, S230A, G232D, G232S, H234Q, K241E, W243G, S246C, G251E, C256G, P261S, I265S, R274G, K275E, I278M, V278L, I282L, K285N, K285T, I290L, C303Y, I315V, N337I, V341I | WT levels 
0.6-18 nM |
| 027 | Nucleoside naïve,  eAg- | D2N, H9R, R18S, N33T, N71D, S78Y, S78T, D83G, V84M, S117Y, I121S, Q125K, M129T, R153L, A194S, T222S, H234R, R270E, K275N, R280K, W284Stop, R289Q, G292D, F296L, I315L, K318R, A320T, M336I, A342T | WT levels
0.8 – 12 nM
 |
| 014 | LVD Refractory | L80I, L229W | LVDR levels 
22 – 45 nM |
| 026 | LVD Refractory | V27A, I53F, S78T, L80V, K168E, A181T, C188S, V191A, A200V, V224A, D263G, G295S, M309L | LVDR levels
2.4 – 31 nM |

**13-15**

## ETV Virologic Rebounds: Year Two

| Study | 022 
eAg pos | 027
eAg neg |
| --- | --- | --- |
| YR 1 Treated | 354 | 325 |
| YR 2 Treated | 267 | 127 |
| YR 1 Rebounds | 6 (2%) | 5 (2%) |
| YR 2 Rebounds | 6 (2%) | 1 (<1%) |
| Genotypic Resistance* | 0 (0%) | 0 (0%) |

**ETV**

**LVD**

**n = ****352   331   341   228****   ****354  322   324    212 **

** ****Wk  ****0     24    48     96****     ****0     24    48     96**

**HBV DNA (Copies/mL)**

**10****3**

**<300**

**300-999**

**10****4**

**10****5**

**10****6**

**10****7**

**10****8**

**10****9**

**10****10**

**10****11**

**Percent of Subjects**

**Study 022 eAg pos**

**38**

**65**

**81**

**24**

**37**

**38**

**Study 022**

**13-6**

## Knodell Necroinflammatory Mean Score

|  | Naïve eAg+ |  | Naïve eAg- |  | LVD-Ref eAg+ |  |
| --- | --- | --- | --- | --- | --- | --- |
|  | ETV         N = 292 | LVD           N = 269 | ETV               N = 265 | LVD                  N = 250 | ETV              N = 110 | LVD         N = 98 |
|  |  |  |  |  |  |  |
| Baseline | 8.2 | 8.1 | 8.1 | 7.8 | 7.2 | 7.4 |
| Week 48 | 4.4 | 4.6 | 4.2 | 4.6 | 4.2 | 6.7 |
| Week 48 change from baseline | -3.7 | -3.5 | -4.0* | -3.2* | -2.9* | 0.6* |

- Analyses were based on patients with baseline Knodell necroinflammatory score ≥ 2and adequate Week 48 biopsy
- * p < 0.01 (ETV vs. LVD)

**Studies 022, 027 and 026**

**2-66**

## Sustained Response Through 24 Weeks Off Treatmentfor Responders at Week 48 – Naïve Patients

**Sustained Response Through 24 Weeks Off Treatment****for Responders at Week 48 – Naïve Patients**

**Studies 022 and 027**

**Naïve eAg+**

**Naïve eAg-**

**Percent**

**N =              74          67                                259         220                                             **

**n = 61**

**n = 49**

**n = 124**

**n = 78**

**2-380**

## Histologic Improvement, HBV DNA, and ALTat Week 48

**Studies 022, 027 and 026**

|  | Naïve eAg+ |  | Naïve eAg- |  | LVD-Ref eAg+ |  |
| --- | --- | --- | --- | --- | --- | --- |
|  | ETVN = 314  | LVDN = 314 | ETVN = 296 | LVDN = 287 | ETVN = 124 | LVDN = 116 |
| 
Histologic Improvement,
ALT ≤ 1 x ULN and HBV
DNA < 400 copies/mL | 138 
( 44)  | 80
 ( 25)  | 170
( 57)  | 112
 ( 39)  | 16
( 13)  | 0 
(  0)  |
| 
Histologic Improvement,
ALT ≤ 1 x ULN and HBV
DNA < 105 copies/mL | 169
( 54)  | 122
 ( 39)  | 179
( 60)  | 130
 ( 45)  | 29
( 23)  | 1 
(  1)  |

- Evaluable Baseline Histology

**Number of patients (%)**

**17-1**

## Growth Rates of HCC

**0**

**2**

**4**

**6**

**8**

**10**

**12**

**14**

**<30**

**30-90**

**90-150**

**150-210**

**>210**

**Doubling Time (days)**

**Number of Cases **

*Sheu J-C et al, Gastro 1985;89:259*

- Median doubling time =
- 117 days (range 29-398)

##                     Six cases of HCC

- Start of Therapy

- Tumor Volume (cc)

- Months

- Months

- 0.01

-   0.1

- 1

- 10

-   100

- 1000

- 10000

- -15.0

- -10.0

- -5.0

- 0.0

- 5.0

- 10.0

- 15.0

- 20.0

-                     Six cases of HCC
*Origin Relative to Start of Therapy – Doubling Time 29 d*

- 3E

- 2L

- 1L

- 4E

- 5E

- 6L

##            Six cases of HCC

- Start of Therapy

- Months

- Months

- -15.0

- -10.0

- -5.0

- 0.0

- 5.0

- 10.0

- 15.0

- 20.0

-            Six cases of HCC
*Origin Relative to Start of Therapy*

- 6L

- -20.0

- doubling time 29 d

- doubling time 117 d