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New 48-Week Efficacy and Safety Data Presented for Intelence (etravirine) as Part of HIV Combination Therapy

BRIDGEWATER, N.J., February 07, 2008 /PRNewswire/ -- New data showed that at 48 weeks, significantly more treatment-experienced adults with HIV-1 with documented resistance to non-nucleoside reverse transcriptase inhibitors (NNRTIs) and protease inhibitors (PIs) had an undetectable viral load (defined as less than 50 HIV-1 RNA copies/mL) with INTELENCE (etravirine) tablets plus a background regimen (BR) compared with placebo plus a BR. These findings from two ongoing double-blind, placebo-controlled, randomized Phase 3 studies (DUET-1 and DUET-2) were presented at the 15th Conference on Retroviruses and Opportunistic Infections in Boston.

In the DUET-1 and -2 studies, 60 percent and 61 percent of patients in the INTELENCE arms had a confirmed undetectable viral load at 48 weeks compared with 39 percent and 41 percent of those in the placebo arms, respectively. In each study, this difference was significant [p<0.0001].

INTELENCE, a new NNRTI from Tibotec, received accelerated approval from the U.S. Food and Drug Administration (FDA) on January 18, 2008. It is the first NNRTI to receive approval in almost ten years. INTELENCE received approval based on the 24-week analysis of HIV viral load and CD4+ cell counts from the pooled DUET-1 and -2 studies. The 48-week results will be filed with the FDA for consideration of traditional approval of INTELENCE.

"Etravirine is an important new option for treatment-experienced patients with NNRTI resistance and these data build upon the 24-week data that had previously been available," said Richard Haubrich, M.D., Professor of Medicine, Division of Infectious Diseases, University of California, San Diego, and investigator in the INTELENCE Phase 3 DUET studies.

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-naïve adult patients.


DUET-1 and -2 Study Design

The DUET-1 and -2 studies, identical in design but conducted in different regions, assessed the 24- and 48-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. 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 studies had a viral load of greater than 5,000 copies/mL while on a stable antiretroviral therapy regimen for at least eight weeks and had evidence of at least one NNRTI- resistance-associated mutation, either at screening or from prior 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 remained double-blinded through 48-weeks.

    48-Week Efficacy Findings


    -- In DUET-1, 60 percent of patients in the INTELENCE arm had a confirmed

       undetectable viral load at 48 weeks compared with 39 percent of those

       in the placebo arm [p<0.0001].


    -- In DUET-2, 61 percent of patients in the INTELENCE arm had a confirmed

       undetectable viral load at 48 weeks compared with 41 percent of those

       in the placebo arm  [p<0.0001].


    -- In DUET-1, the mean increase in CD4+ cell count from baseline was

       103 cells/mm3 in the INTELENCE arm compared with 74 cells/mm3 in the

       placebo arm [p=0.0025].


    -- In DUET-2, the mean increase in CD4+ cell count from baseline was

       94 cells/mm3 in the INTELENCE arm compared with 72 cells/mm3 in the

       placebo arm [p=0.0160].


48-Week Safety Findings

In DUET-1, the most commonly reported adverse events among patients in the INTELENCE arm vs. placebo arm were rash of any type (22 percent vs. 11 percent), diarrhea (14 percent vs. 24 percent), and nausea (15 percent vs. 15 percent).

In DUET-2, the most commonly reported adverse events among patients in the INTELENCE arm vs. placebo arm were diarrhea (22.0 percent vs. 22.6 percent), rash of any type (16.6 percent vs. 11.1 percent) and nausea (14.6 percent vs. 10.8 percent).

Important Safety Information

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

    -- Severe and potentially life-threatening skin reactions, including

       Stevens-Johnson Syndrome, hypersensitivity reaction, and erythema

       multiforme, have occurred (<0.1 percent) 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 percent


    -- 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


    -- 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


    -- The most common adverse events (>10 percent) of any intensity that

       occurred at a higher rate than placebo at 24-weeks were rash (16.9

       percent vs. 9.3 percent) and nausea (13.9 percent vs. 11.1 percent)


    -- 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 percent vs. 3.1 percent), diarrhea

       (5.2 percent vs. 9.6 percent), nausea (4.7 percent vs. 3.5 percent),

       fatigue (3.3 percent vs. 4.0 percent), abdominal pain (3.0 percent vs.

       2.5 percent), peripheral neuropathy (2.8 percent vs. 1.8 percent),

       hypertension (2.8 percent vs. 2.2 percent), headache (2.7 percent vs.

       4.1 percent), and vomiting (2.3 percent vs. 2.0 percent).



    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 Prescribing Information for more details at INTELENCE-info.com.

About INTELENCE

INTELENCE was developed by Tibotec Pharmaceuticals Ltd. and is marketed in the U.S. by Tibotec Therapeutics, a division of Ortho Biotech Products, L.P. Applications for approval of INTELENCE have been submitted to the European Agency for the Evaluation of Medicinal Products (EMEA) and to regulatory authorities in other countries, including Canada, Switzerland, Russia, Australia, and South Korea.

Tibotec Therapeutics

Tibotec Therapeutics, a division of Ortho Biotech Products, L.P., a subsidiary of Johnson & Johnson, 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.

Tibotec Pharmaceuticals Ltd.

Tibotec Pharmaceuticals Ltd., a subsidiary of Johnson & Johnson, based in Cork, Ireland, is a pharmaceutical research and development company. The Company's main research and development facilities are in Mechelen, Belgium with offices in Yardley, PA. Tibotec is dedicated to the discovery and development of innovative HIV/AIDS drugs and anti-infectives for diseases of high unmet medical need.

Forward Looking Statement

This press release contains "forward-looking statements" as defined in the Private Securities Litigation Reform Act of 1995. These statements are based on current expectations of future events. If underlying assumptions prove inaccurate or unknown risks or uncertainties materialize, actual results could vary materially from Tibotec Pharmaceuticals Ltd.'s expectations and projections. Risks and uncertainties include general industry conditions and competition; economic conditions, such as interest rate and currency exchange rate fluctuations; technological advances and patents attained by competitors; challenges inherent in new product development, including obtaining regulatory approvals; domestic and foreign health care reforms and governmental laws and regulations; and trends toward health care cost containment. A further list and description of these risks, uncertainties and other factors can be found in Exhibit 99 of Johnson & Johnson's Annual Report on Form 10-K for the fiscal year ended December 31, 2006. Copies of this Form 10-K, as well as subsequent filings, are available online at www.sec.gov, www.jnj.com or on request from Tibotec Pharmaceuticals Ltd. or Johnson & Johnson. Tibotec Pharmaceuticals Ltd. does not undertake to update any forward-looking statements as a result of new information or future events or developments.

    Media Contact:       Pamela Van Houten

                         908-541-4137 (office)

                         908-295-7367 (mobile)


    Investor Relations:  Lesley Fishman

                         732-524-3922 (office)

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

Web site: http://www.INTELENCE-info.com/

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Posted: February 2008

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