96-Week Safety and Efficacy Findings Presented for Intelence (etravirine) As Part of HIV Combination Therapy

BRIDGEWATER, N.J., July 20 /PRNewswire/ -- Ninety-six week pooled results from two Phase 3 studies (DUET-1 and DUET-2) showed that significantly more treatment-experienced HIV-1-infected adults with non-nucleoside reverse transcriptase inhibitor (NNRTI) and protease inhibitor (PI) resistance had an undetectable viral load (<50 hiv-1 rna copies>

In the pooled analysis of the DUET studies at 96 weeks, 57 percent of patients in the INTELENCE arm had an undetectable viral load (<50 copies>

"These data are important because they add to the body of knowledge on INTELENCE, an important option for treatment-experienced patients with NNRTI and PI resistance," said DUET clinical investigator Tony Mills, MD, HIV specialist in private practice, Los Angeles, and Assistant Professor of Clinical Medicine, UCLA.

When it received accelerated approval by the U.S. Food and Drug Administration (FDA) in January 2008, INTELENCE was the first NNRTI to be introduced in nearly ten years. Since then, INTELENCE has been approved in nearly 50 countries. In January 2009, an application was submitted to the FDA for traditional approval, which included 48-week data from DUET-1 and DUET-2. The FDA will need to determine if these data are sufficient to support traditional approval.

When it received accelerated approval by the U.S. Food and Drug Administration (FDA) in January 2008, INTELENCE was the first NNRTI to be introduced in nearly ten years. Since then, INTELENCE has been approved in nearly 50 countries. In January 2009, an application was submitted to the FDA for traditional approval, which included 48-week data from DUET-1 and DUET-2.

INTELENCE, in combination with other antiretroviral (ARV) agents, is indicated for the treatment of human immunodeficiency virus type 1 (HIV-1) infection in antiretroviral treatment-experienced adult patients who have evidence of viral replication and HIV-1 strains resistant to a NNRTI and other ARV agents.

This indication is based on Week 24 analyses from two randomized, double-blind, placebo-controlled trials of INTELENCE. Both studies were conducted in clinically advanced, three-class antiretroviral (NNRTI, N[t]RTI, PI) treatment-experienced adults.

The following points should be considered when initiating therapy with INTELENCE:

  --  Treatment history and, when available, resistance testing, should
      guide the use of INTELENCE.
  --  The use of other active antiretroviral agents with INTELENCE is
      associated with an increased likelihood of treatment response.
  --  In patients who have experienced virologic failure on an
      NNRTI-containing regimen, do not use INTELENCE in combination with
      only N[t]RTIs.

  --  The risks and benefits of INTELENCE have not been established in
      pediatric patients or in treatment-naive adults.

  DUET-1 and -2 Study Design

The DUET-1 and -2 studies, identical in design and conducted across the Americas, Australia, Canada, Europe, Thailand and Europe, assessed the 24-week efficacy and safety of INTELENCE in combination with a BR in treatment-experienced adult HIV-1 patients with documented evidence of NNRTI and PI resistance. They were large randomized, controlled studies and the primary endpoint was the proportion of patients who achieved a confirmed undetectable viral load (less than 50 copies/mL).

Patients with HIV-1 who were eligible for the DUET trials had a viral load of greater than 5,000 copies/mL, were on a stable antiretroviral therapy regimen, and had evidence of at least one NNRTI-resistance-associated mutation, either at screening or from historical resistance tests as well as evidence of three or more primary PI mutations (D30N, V32I, L33F, M46I/L, I47A/V, G48V, I50L/V, V82A/F/L/S/T, I84V, N88S, or L90M) at screening.

Participants in the DUET studies were randomized to receive INTELENCE 200 mg twice daily (599 patients) or placebo (604 patients), each given in addition to a BR. For all patients, the BR included darunavir/ritonavir, plus at least two investigator-selected antiretroviral drugs (N(t)RTIs with or without enfuvirtide).

The study was designed to evaluate INTELENCE efficacy and safety over 48 weeks with an optional extension to 96 weeks. The study remained double-blinded until the last study participant reached week 48.

DUET-1 and -2: 96-Week Efficacy Data

The 96-week pooled analysis of the DUET studies showed the following efficacy results:

  --  Fifty-seven percent of patients in the INTELENCE arm had an
      undetectable viral load (<50 copies>

INTELENCE does not cure HIV infection or AIDS, and does not prevent passing HIV to others.

  Warnings & Precautions
  --  Severe Skin Reactions: Severe and potentially life-threatening skin
      reactions, including Stevens-Johnson Syndrome, hypersensitivity
      reaction, and erythema multiforme, have occurred (<0.1%) in patients
      taking INTELENCE. Treatment with INTELENCE should be discontinued and
      appropriate therapy initiated if severe rash develops. In general, in
      clinical trials, rash was mild to moderate, occurred primarily in the
      second week of therapy, and was infrequent after Week 4.  Rash
      generally resolved within 1-2 weeks on continued therapy. 
      Discontinuation rate due to rash was 2%.
  --  Fat Redistribution: Redistribution and/or accumulation of body fat
      have been observed in patients receiving antiretroviral (ARV) therapy.
      The causal relationship, mechanism, and long-term consequences of
      these events have not been established.

  --  Immune reconstitution syndrome has been reported in patients treated
      with ARV therapy, including INTELENCE.

  Use in Specific Populations

  --  Hepatic Impairment: INTELENCE should be used with caution in patients
      with severe hepatic impairment (Child-Pugh Class C) as
      pharmacokinetics of INTELENCE have not been evaluated in these
      patients.

  Adverse Reactions
  --  The most common adverse events (>10%) of any intensity that occurred
      at a higher rate than placebo at 24-weeks were rash (16.9% vs. 9.3%)
      and nausea (13.9% vs. 11.1%).

  --  The most common treatment-emergent adverse reactions (Grade 2-4) that
      occurred in patients receiving an INTELENCE-containing regimen vs.
      placebo at 24-weeks were rash (9.0% vs. 3.1%), diarrhea (5.2% vs.
      9.6%), nausea (4.7% vs. 3.5%), fatigue (3.3% vs. 4.0%), abdominal pain
      (3.0% vs. 2.5%), peripheral neuropathy (2.8% vs. 1.8%), hypertension
      (2.8% vs. 2.2%), headache (2.7% vs. 4.1%), and vomiting (2.3% vs.
      2.0%).

  Drug Interactions
  --  INTELENCE should not be co-administered with the following ARVs:
      tipranavir/ritonavir, fosamprenavir/ritonavir, atazanavir/ritonavir,
      full-dose ritonavir (600 mg bid), protease inhibitors administered
      without ritonavir, and other NNRTIs.
  --  INTELENCE should not be co-administered with carbamazepine,
      phenobarbital, phenytoin, rifampin, rifapentine, rifabutin (when part
      of a regimen containing protease inhibitor/ritonavir) or products
      containing St. John's wort (Hypericum perforatum).
  --  INTELENCE and lopinavir/ritonavir should be co-administered with
      caution.

  --  Co-administration of INTELENCE with other agents such as substrates,
      inhibitors, or inducers of CYP3A4, CYP2C9, and/or CYP2C19 may alter
      the therapeutic effect or adverse events profile of INTELENCE or the
      co-administered drug(s). This is not a complete list of potential drug
      interactions.

Please see full Product Information about INTELENCE for more details. A copy of full Product Information can be obtained by visiting www.INTELENCE-info.com.

You are encouraged to report negative side effects of prescription drugs to the FDA. Visit www.fda.gov/medwatch, or call 1-800-FDA-1088.

About Tibotec Therapeutics

Tibotec Therapeutics, a division of Ortho Biotech Products, L.P., headquartered in Bridgewater, N.J., is dedicated to delivering innovative virology therapeutics that help healthcare professionals address serious unmet needs in people living with HIV.

About Tibotec Pharmaceuticals

Tibotec Pharmaceuticals, based in Cork, Ireland, is a pharmaceutical research and development company, with offices in Yardley, PA, USA and its main research and development operations in Mechelen, Belgium. Tibotec is dedicated to the discovery and development of innovative HIV/AIDS drugs and anti-infectives for diseases of high unmet medical need.

  Media Contact:         Pamela Van Houten
                         908-541-4137 (office)
                         908-295-7367 (mobile)

  Investor Relations:    Louise Mehrotra 732-524-6491
                         Lesley Fishman 732-524-3922

Source: Tibotec Therapeutics

CONTACT: Media: Pamela Van Houten, +1-908-541-4137 (office), +1-908-295-7367 (mobile); Investor Relations: Louise Mehrotra, +1-732-524-6491, or Lesley Fishman, +1-732-524-3922

Web Site: http://www.intelence-info.com/

Posted: July 2009

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