Healthcare Industry News: darunavir
News Release - February 7, 2008
New 48-Week Efficacy and Safety Data Presented for INTELENCE(TM) (etravirine) as Part of HIV Combination TherapyBRIDGEWATER, N.J., Feb. 7 (HSMN NewsFeed) -- 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-na´ve 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).
-- 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.
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, 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.
Source: Tibotec Therapeutics
Issuer of this News Release is solely responsible for its
Please address inquiries directly to the issuing company.