Two Studies Show Clevudine (L-FMAU) Is Potent Inhibitor of HBV and Well Tolerated

[Guest guest]

Two Studies Show Clevudine (L-FMAU) Is Potent Inhibitor of HBV and Well

Tolerated

By Mark , MD

Clevudine is a pyrimidine analogue that is a potent inhibitor of HBV

replication in vitro. In woodchucks, clevudine has potent antiviral

activity

with a durable post treatment response.

The first study reported at HEP DART (December 14-18, 2003 in Kauai, Hawaii)

was a safety and efficacy study of clevudine at 2 separate doses: 30mg or

50mg, compared with placebo in individuals infected with hepatitis B.

Eligible individuals were female or male with e antigen positive chronic

hepatitis B with HBV DNA levels greater or equal to 3 million copies/ml.

99 Individuals were enrolled, 68 of whom have completed 36 weeks of the

study.

Individuals received 12 weeks of study drug followed by 24 weeks off

treatment. Median HBV DNA level at baseline were 8.2, 8.4 and 8.4 log

copies/ml in the placebo 30mg and 50mg arms.

The median change at week 12 in HBV viral load were -0.52, -4.24 and -4.45

log respectively. Results of the follow up are affected by the high rate of

e

antigen loss in the placebo group (5 of 19).

However, post treatment response was sustained in both treatment arms (3.5

and

3.19 log reduction in HBV DNA at 24 weeks, and 2.56 and 1.75 log at 24 weeks

off therapy compared with 0.5 log and 0.4 log in the placebo arm).

In the placebo, 30mg and 50mg cohorts 0, 68 and 71% had HBV DNA levels below

the limit of detection at the end of 12 weeks treatment and 5, 12, and 13%

at

week 36. Normalisation of ALT was observed in 16, 72 and 67% at week 12 and

37, 78 and 67% at week 36.

Clevudine was well tolerated and clearly has potent antiviral activity with

sustained viral suppression of therapy.

Second Study of Clevudine

A second study of clevudine was reported with results at 12 weeks. This was

a

multi-centre, international, randomised double blind study that compared

treatment with 10, 30 and 50mg of clevudine for 12 weeks.

Individuals were chronically infected with HBV with baseline serum HBV DNA

levels greater than3 x 106/ml, and were nucleoside treatment-naïve. 31

individuals were enrolled of whom 55% were male, 84% Asian and 81% e antigen

positive. Baseline viral load was 8.7, 7.9 and 8.7 log 10 copies per/ml,

median ALT 53, 63 and 80 IU/L.

After 12 weeks of dosing median viral load change was -3.2, -3.7 and -4.1

log. 1 out of 10, 5 out of 11 and 2 out of 10 individuals had viral load

below the lower limit of detection (4,700 copies per/ml). 2 individuals in

the

30mg qd cohort seroconverted to anti-HB e and none had isolated E antigen

loss.

Clevudine was well tolerated with only one individual having a transient

grade

3 increase in ALT. No treatment emergent mutations in the HBV DNA conserved

domain were observed.

01/12/04

Source

HEP DART 2003. December 14-18, 2003. Kauai, Hawaii.

[Guest guest]

Two Studies Show Clevudine (L-FMAU) Is Potent Inhibitor of HBV and Well

Tolerated

By Mark , MD

Clevudine is a pyrimidine analogue that is a potent inhibitor of HBV

replication in vitro. In woodchucks, clevudine has potent antiviral

activity

with a durable post treatment response.

The first study reported at HEP DART (December 14-18, 2003 in Kauai, Hawaii)

was a safety and efficacy study of clevudine at 2 separate doses: 30mg or

50mg, compared with placebo in individuals infected with hepatitis B.

Eligible individuals were female or male with e antigen positive chronic

hepatitis B with HBV DNA levels greater or equal to 3 million copies/ml.

99 Individuals were enrolled, 68 of whom have completed 36 weeks of the

study.

Individuals received 12 weeks of study drug followed by 24 weeks off

treatment. Median HBV DNA level at baseline were 8.2, 8.4 and 8.4 log

copies/ml in the placebo 30mg and 50mg arms.

The median change at week 12 in HBV viral load were -0.52, -4.24 and -4.45

log respectively. Results of the follow up are affected by the high rate of

e

antigen loss in the placebo group (5 of 19).

However, post treatment response was sustained in both treatment arms (3.5

and

3.19 log reduction in HBV DNA at 24 weeks, and 2.56 and 1.75 log at 24 weeks

off therapy compared with 0.5 log and 0.4 log in the placebo arm).

In the placebo, 30mg and 50mg cohorts 0, 68 and 71% had HBV DNA levels below

the limit of detection at the end of 12 weeks treatment and 5, 12, and 13%

at

week 36. Normalisation of ALT was observed in 16, 72 and 67% at week 12 and

37, 78 and 67% at week 36.

Clevudine was well tolerated and clearly has potent antiviral activity with

sustained viral suppression of therapy.

Second Study of Clevudine

A second study of clevudine was reported with results at 12 weeks. This was

a

multi-centre, international, randomised double blind study that compared

treatment with 10, 30 and 50mg of clevudine for 12 weeks.

Individuals were chronically infected with HBV with baseline serum HBV DNA

levels greater than3 x 106/ml, and were nucleoside treatment-naïve. 31

individuals were enrolled of whom 55% were male, 84% Asian and 81% e antigen

positive. Baseline viral load was 8.7, 7.9 and 8.7 log 10 copies per/ml,

median ALT 53, 63 and 80 IU/L.

After 12 weeks of dosing median viral load change was -3.2, -3.7 and -4.1

log. 1 out of 10, 5 out of 11 and 2 out of 10 individuals had viral load

below the lower limit of detection (4,700 copies per/ml). 2 individuals in

the

30mg qd cohort seroconverted to anti-HB e and none had isolated E antigen

loss.

Clevudine was well tolerated with only one individual having a transient

grade

3 increase in ALT. No treatment emergent mutations in the HBV DNA conserved

domain were observed.

01/12/04

Source

HEP DART 2003. December 14-18, 2003. Kauai, Hawaii.

[Guest guest]

Two Studies Show Clevudine (L-FMAU) Is Potent Inhibitor of HBV and Well

Tolerated

By Mark , MD

Clevudine is a pyrimidine analogue that is a potent inhibitor of HBV

replication in vitro. In woodchucks, clevudine has potent antiviral

activity

with a durable post treatment response.

The first study reported at HEP DART (December 14-18, 2003 in Kauai, Hawaii)

was a safety and efficacy study of clevudine at 2 separate doses: 30mg or

50mg, compared with placebo in individuals infected with hepatitis B.

Eligible individuals were female or male with e antigen positive chronic

hepatitis B with HBV DNA levels greater or equal to 3 million copies/ml.

99 Individuals were enrolled, 68 of whom have completed 36 weeks of the

study.

Individuals received 12 weeks of study drug followed by 24 weeks off

treatment. Median HBV DNA level at baseline were 8.2, 8.4 and 8.4 log

copies/ml in the placebo 30mg and 50mg arms.

The median change at week 12 in HBV viral load were -0.52, -4.24 and -4.45

log respectively. Results of the follow up are affected by the high rate of

e

antigen loss in the placebo group (5 of 19).

However, post treatment response was sustained in both treatment arms (3.5

and

3.19 log reduction in HBV DNA at 24 weeks, and 2.56 and 1.75 log at 24 weeks

off therapy compared with 0.5 log and 0.4 log in the placebo arm).

In the placebo, 30mg and 50mg cohorts 0, 68 and 71% had HBV DNA levels below

the limit of detection at the end of 12 weeks treatment and 5, 12, and 13%

at

week 36. Normalisation of ALT was observed in 16, 72 and 67% at week 12 and

37, 78 and 67% at week 36.

Clevudine was well tolerated and clearly has potent antiviral activity with

sustained viral suppression of therapy.

Second Study of Clevudine

A second study of clevudine was reported with results at 12 weeks. This was

a

multi-centre, international, randomised double blind study that compared

treatment with 10, 30 and 50mg of clevudine for 12 weeks.

Individuals were chronically infected with HBV with baseline serum HBV DNA

levels greater than3 x 106/ml, and were nucleoside treatment-naïve. 31

individuals were enrolled of whom 55% were male, 84% Asian and 81% e antigen

positive. Baseline viral load was 8.7, 7.9 and 8.7 log 10 copies per/ml,

median ALT 53, 63 and 80 IU/L.

After 12 weeks of dosing median viral load change was -3.2, -3.7 and -4.1

log. 1 out of 10, 5 out of 11 and 2 out of 10 individuals had viral load

below the lower limit of detection (4,700 copies per/ml). 2 individuals in

the

30mg qd cohort seroconverted to anti-HB e and none had isolated E antigen

loss.

Clevudine was well tolerated with only one individual having a transient

grade

3 increase in ALT. No treatment emergent mutations in the HBV DNA conserved

domain were observed.

01/12/04

Source

HEP DART 2003. December 14-18, 2003. Kauai, Hawaii.

[Guest guest]

Two Studies Show Clevudine (L-FMAU) Is Potent Inhibitor of HBV and Well

Tolerated

By Mark , MD

Clevudine is a pyrimidine analogue that is a potent inhibitor of HBV

replication in vitro. In woodchucks, clevudine has potent antiviral

activity

with a durable post treatment response.

The first study reported at HEP DART (December 14-18, 2003 in Kauai, Hawaii)

was a safety and efficacy study of clevudine at 2 separate doses: 30mg or

50mg, compared with placebo in individuals infected with hepatitis B.

Eligible individuals were female or male with e antigen positive chronic

hepatitis B with HBV DNA levels greater or equal to 3 million copies/ml.

99 Individuals were enrolled, 68 of whom have completed 36 weeks of the

study.

Individuals received 12 weeks of study drug followed by 24 weeks off

treatment. Median HBV DNA level at baseline were 8.2, 8.4 and 8.4 log

copies/ml in the placebo 30mg and 50mg arms.

The median change at week 12 in HBV viral load were -0.52, -4.24 and -4.45

log respectively. Results of the follow up are affected by the high rate of

e

antigen loss in the placebo group (5 of 19).

However, post treatment response was sustained in both treatment arms (3.5

and

3.19 log reduction in HBV DNA at 24 weeks, and 2.56 and 1.75 log at 24 weeks

off therapy compared with 0.5 log and 0.4 log in the placebo arm).

In the placebo, 30mg and 50mg cohorts 0, 68 and 71% had HBV DNA levels below

the limit of detection at the end of 12 weeks treatment and 5, 12, and 13%

at

week 36. Normalisation of ALT was observed in 16, 72 and 67% at week 12 and

37, 78 and 67% at week 36.

Clevudine was well tolerated and clearly has potent antiviral activity with

sustained viral suppression of therapy.

Second Study of Clevudine

A second study of clevudine was reported with results at 12 weeks. This was

a

multi-centre, international, randomised double blind study that compared

treatment with 10, 30 and 50mg of clevudine for 12 weeks.

Individuals were chronically infected with HBV with baseline serum HBV DNA

levels greater than3 x 106/ml, and were nucleoside treatment-naïve. 31

individuals were enrolled of whom 55% were male, 84% Asian and 81% e antigen

positive. Baseline viral load was 8.7, 7.9 and 8.7 log 10 copies per/ml,

median ALT 53, 63 and 80 IU/L.

After 12 weeks of dosing median viral load change was -3.2, -3.7 and -4.1

log. 1 out of 10, 5 out of 11 and 2 out of 10 individuals had viral load

below the lower limit of detection (4,700 copies per/ml). 2 individuals in

the

30mg qd cohort seroconverted to anti-HB e and none had isolated E antigen

loss.

Clevudine was well tolerated with only one individual having a transient

grade

3 increase in ALT. No treatment emergent mutations in the HBV DNA conserved

domain were observed.

01/12/04

Source

HEP DART 2003. December 14-18, 2003. Kauai, Hawaii.