TORONTO, Aug. 14 /PRNewswire/ -- Additional safety and efficacy data for PREZISTA(TM) (darunavir) 300mg tablets, an anti-HIV medication, will be presented Tuesday, 15th August, at the 16th International AIDS Conference (AIDS 2006) in Toronto, Canada. In an oral presentation, researchers will report data from patients who had reached 48 weeks of treatment in an ad hoc (unplanned) pooled analysis from the POWER 1 and POWER 2 studies.
The U.S. Food and Drug Administration (FDA) granted accelerated approval to PREZISTA, a protease inhibitor formerly known as TMC114, in June 2006. PREZISTA, co-administered with 100 mg ritonavir (PREZISTA/rtv) and with other antiretroviral agents, is indicated for the treatment of human immunodeficiency virus (HIV) infection in antiretroviral treatment-experienced adult patients, such as those with HIV-1 strains resistant to more than one protease inhibitor (see the full indication and important safety information below).
PREZISTA was granted accelerated approval based on the 24-week primary analysis of HIV viral load and CD4+ cell counts from the pooled analysis of the POWER 1 and POWER 2 dose-finding studies (see 24-week primary analysis results below). FDA accelerated approval procedures allow for earlier approval of drugs that provide a meaningful therapeutic advantage over existing treatment for serious or life-threatening diseases. Forty-eight week data from ongoing Phase 3 studies and 96- week data from POWER 1, 2, and 3 will be required before the FDA can consider traditional approval for PREZISTA.
In the POWER 1 and 2 studies, treatment-experienced adult patients were randomized to receive PREZISTA and ritonavir (600mg/100mg) twice daily plus an individualized combination of anti-HIV drugs called an optimized background regimen (OBR) (131 patients) or commercially available investigator-selected protease inhibitors boosted with ritonavir plus OBR (124 patients).
Patients enrolled in the POWER 1 and POWER 2 studies had previously been treated with at least one protease inhibitor, one non-nucleoside reverse transcriptase inhibitor (NNRTI) and one nucleoside reverse transcriptase inhibitor (NRTI), had one or more primary protease inhibitor mutations, and were failing a PI-based regimen. Investigator selected OBR and control protease inhibitors were chosen based on resistance testing and prior treatment history. The OBR consisted of at least two NRTIs with or without enfuvirtide.
Ad Hoc Analysis of Patients Reaching 48 Weeks of Treatment
The data to be presented are from the patients in POWER 1 and 2 who had reached 48 weeks of treatment at the time of the ad hoc analysis. Among 110 patients who had reached 48 weeks of treatment in the PREZISTA/rtv arm (total n=131) vs. 120 patients who had reached 48 weeks of treatment in the control arm (total n=124), intent-to-treat data will be presented:
* 61 percent vs. 15 percent had a virologic response defined as equal to or greater than 1.0 log(10) reduction (90 percent reduction) in viral load from baseline * 46 percent vs. 10 percent reached undetectable viral load (less than 50 copies/mL) * CD4+ cell mean increase of 102 cells/mm(3) vs. 19 cells/mm(3) from baseline
Among patients reaching 48 weeks, the most commonly reported adverse events among patients in the PREZISTA/rtv arm vs. control arm were diarrhea (20 percent vs. 28 percent), nausea (18 percent vs. 13 percent), headache (15 percent vs. 20 percent), nasopharyngitis (14 percent vs. 11 percent) and fatigue (12 percent vs. 17 percent). Discontinuations because of adverse events were seven percent in the PREZISTA/rtv arm vs. five percent in the control arm.
Longer-term data are required to further evaluate the safety and efficacy of PREZISTA/rtv.
24-Week Primary Analysis Findings
The primary analysis from POWER 1 and 2 showed that at 24 weeks, patients in the PREZISTA/rtv arm were significantly more likely to achieve a virologic response, achieve undetectable viral load (less than 50 copies/mL) and have an increase in CD4+ cell counts from baseline compared to the patients in the control arm:
* 69.5 percent vs. 21 percent achieved a virologic response defined as equal to or greater than 1.0 log(10) reduction (90 percent reduction) in viral load from baseline * 45 percent vs. 12.1 percent achieved undetectable viral load (less than 50 copies/mL) * CD4+ cell mean increase of 92 cells/mm(3) vs. 17 cells/mm(3) from baseline Indication
PREZISTA, co-administered with 100 mg ritonavir (PREZISTA/rtv) and with other antiretroviral agents, is indicated for the treatment of human immunodeficiency virus (HIV) infection in antiretroviral treatment-experienced adult patients, such as those with HIV-1 strains resistant to more than one protease inhibitor.
This indication is based on Week 24 analyses of plasma HIV RNA levels and CD4+ cell counts from two controlled trials of PREZISTA/rtv in combination with other antiretroviral drugs. Both studies were conducted in clinically advanced, treatment-experienced (NRTIs, NNRTIs, and PIs) adult patients with evidence of HIV-1 replication despite ongoing antiretroviral therapy.
The following points should be considered when initiating therapy with PREZISTA/rtv:
* Treatment history and, when available, genotypic or phenotypic testing should guide the use of PREZISTA/rtv. * The use of other active agents with PREZISTA/rtv is associated with a greater likelihood of treatment response. * The risks and benefits of PREZISTA/rtv have not been established in treatment-naive adult patients or pediatric patients. Important Safety Information
PREZISTA does not cure HIV infection or AIDS, and does not prevent passing HIV to others.
PREZISTA is contraindicated in patients with known hypersensitivity to any of its ingredients.
PREZISTA/rtv is contraindicated with astemizole, terfenadine, dihydroergotamine, ergonovine, ergotamine, methylergonovine, cisapride, pimozide, midazolam, and triazolam. Coadministration is not recommended with carbamazepine, phenobarbital, phenytoin, rifampin, lopinavir/ritonavir, saquinavir, lovastatin, pravastatin, simvastatin, or products containing St. John’s wort (Hypericum perforatum).
Caution should be used when prescribing agents such as sildenafil, vardenafil, tadalafil, or other substrates, inhibitors, or inducers of CYP3A in patients receiving PREZISTA/rtv. This list of potential drug interactions is not complete.
PREZISTA must be co-administered with 100 mg ritonavir and food to exert its therapeutic effect. Please refer to ritonavir prescribing information for additional information on precautionary measures.
Severe skin rash, including erythema multiforme and Stevens-Johnson Syndrome, has been reported in subjects receiving PREZISTA during the clinical development program. In some cases, fever and elevations of transanimases have also been reported. In clinical trials (n=924), rash (all grades, regardless of causality) occurred in seven percent of subjects treated with PREZISTA; discontinuation due to rash was 0.3 percent. Rashes were generally mild-to-moderate, self-limiting and maculopapular. PREZISTA should be discontinued if severe rash develops.
PREZISTA should be used with caution in patients with known sulfonamide allergy.
New-onset or exacerbations of pre-existing diabetes mellitus and hyperglycemia, and increased bleeding in hemophiliacs have been reported in patients receiving protease inhibitors. A causal relationship between protease inhibitors and these events has not been established.
PREZISTA should be used with caution in patients with hepatic impairment. There are no data regarding the use of PREZISTA in patients with varying degrees of hepatic impairment; therefore, specific dosage recommendations cannot be made.
Redistribution and/or accumulation of body fat have been observed in patients receiving 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.
The potential for HIV-cross-resistance among protease inhibitors has not been fully explored in PREZISTA/rtv treated patients.
In the pooled analysis of POWER 1 and 2 studies, the most frequently reported drug-related adverse events of at least moderate to severe intensity in patients receiving PREZISTA/rtv-containing regimen were headache (3.8 percent), diarrhea (2.3 percent), abdominal pain (2.3 percent), constipation (2.3 percent), and vomiting (1.5 percent).
Please see full Prescribing Information for more details.
About PREZISTA
PREZISTA was developed by Tibotec Pharmaceuticals Ltd. and is marketed in the U.S. by Tibotec Therapeutics, a division of Ortho Biotech Products, L.P.
An application for marketing authorization was filed with the European Agency for the Evaluation of Medicinal Products (EMEA) in January 2006. Applications for approval have also been submitted or are planned for submission in several other countries around the world in the coming months. Following regulatory approval, Tibotec, a division of Janssen-Cilag, will commercialize PREZISTA in Europe and other countries; Tibotec, a division of Janssen-Ortho Inc. will commercialize PREZISTA in Canada.
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 Ltd.
Tibotec Pharmaceuticals Ltd., 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.
Tibotec Pharmaceuticals is developing a Global Access Program to facilitate access to its antiretrovirals for patients living with HIV/AIDS in developing countries. The Global Access Program for PREZISTA includes access pricing, registration, medical education for appropriate use and voluntary licensing.
Contact: Pamela Van Houten, mobile: 908-295-7367
Tibotec Pharmaceuticals Ltd.
CONTACT: Pamela Van Houten, +1-908-295-7367, for Tibotec PharmaceuticalsLtd.
