Replies to post #499 on Idenix Pharmaceuticals (IDIX)

[gofishmarko]

Good.

Now it's officially a blemish.

[DewDiligence]

Re: Baraclude label

In conjunction with a change to the Baraclude label relating to cross-resistance in HBV-HIV co-infected patients (#msg-17360663), Baraclude received a minor FDA label expansion on 2/23/07. The original (2005) FDA label said this:

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BARACLUDE (entecavir) is indicated for the treatment of chronic hepatitis B virus infection in adults with evidence of active viral replication and either evidence of persistent elevations in serum aminotransferases (ALT or AST) or histologically active disease. This indication is based on histologic, virologic, biochemical, and serologic responses after one year of treatment in nucleoside-treatment-naive and lamivudine-resistant adult patients with HBeAg-positive or HBeAg-negative chronic HBV infection with compensated liver disease and on more limited data in adult patients with HIV/HBV co-infection who have received prior lamivudine therapy [emphasis added].
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The new Baraclude label removes the phrase “after one year of treatment”; the change is presumably based on BMY’s two- and three-year results that were presented at AASLD (#msg-14400271).

The new Baraclude label can be accessed at:
http://www.fda.gov/cder/foi/label/2007/021797s001,021798s001lbl.pdf
(The changed language is on page 11.)

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Tyzeka has an FDA label that is identical to the 2005 Baraclude label: i.e. it includes the “one year” qualifier. This could give BMY’s sales reps something to tout until NVS and IDIX get the “one year” language removed from the Tyzeka label. Based on the two-year Tyzeka data from the GLOBE trial presented at AASLD (#msg-14377860), this ought to be doable.

[DewDiligence]

New black-box warning for Baraclude:

The Baraclude FDA label has been updated with a new black-box warning against use in HIV/HBV co-infected patients not being treated with a standard anti-HIV cocktail.

Excerpt from FDA letter for updated label:
http://www.fda.gov/cder/foi/appletter/2007/021797s003,%20021798s003ltr.pdf

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These submissions amend the labeling to include safety information related to the use of entecavir (ETV) in patients with human immunodeficiency virus (HIV)/hepatitis B virus (HBV) coinfection who are not receiving simultaneous highly active antiretroviral therapy (HAART). Specifically, a recommendation against the use of BARACLUDE in HIV/HBV co-infected patients who are not also receiving adequate therapy for their HIV is added to the Boxed Warnings and WARNINGS sections.
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Actual black-box text from updated Baraclude label:
http://www.fda.gov/cder/foi/label/2007/021797s003,021798s003lbl.pdf

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Limited clinical experience suggests there is a potential for the development of resistance to HIV (human immunodeficiency virus) nucleoside reverse transcriptase inhibitors if BARACLUDE is used to treat chronic hepatitis B virus infection in patients with HIV infection that is not being treated. Therapy with BARACLUDE is not recommended for HIV/HBV co-infected patients who are not also receiving highly active antiretroviral therapy (HAART).
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Tyzeka has no antiviral activity against HIV and hence it does not incur the risk of producing HIV mutations that are resistant to therapy. Advantage: IDIX.