Tibotec Therapeutics announces start of largest US study on HIV treatment in women

September 28, 2006

Tibotec Therapeutics announces initiation of the largest U.S. clinical study examining HIV treatment in treatment-experienced adult women GRACE trial to explore gender-related differences in response to PREZISTA™-based HIV therapy

Bridgewater, NJ, [Thursday, September 28, 2006] -- Tibotec Therapeutics Clinical Affairs, a division of Ortho Biotech Clinical Affairs, LLC, announced today the initiation of the largest clinical study conducted to date in treatment-experienced adult women with HIV to evaluate gender differences in response to an HIV medication.

GRACE (Gender, Race And Clinical Experience), a multi-center, open-label Phase IIIb trial, will compare gender differences in the efficacy, safety and tolerability of PREZISTA (darunavir) tablets administered with other antiretroviral agents over a 48-week treatment period. The study also will explore racial differences in treatment outcomes.

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. PREZISTA received accelerated approval based on the 24-week analysis of HIV viral load and CD4+ cell counts from the pooled analysis of the TMC114-C213 (POWER 1) and TMC114-C202 (POWER 2) studies. Longer-term data will be required before the FDA can consider traditional approval for PREZISTA (see the full indication and important safety information below).

There is an urgent need to conduct clinical trials designed specifically for women with HIV. The ratio of women to men among Americans diagnosed with HIV has grown substantially since the HIV epidemic first emerged.

Today, women account for almost 30 percent of new HIV diagnoses in the U.S., and rates of HIV infection are particularly high among women of color. However, women have been underrepresented in HIV clinical trials despite research suggesting that women may have different tolerability issues to HIV medications than men.

"GRACE is a landmark study because HIV treatment trials - including those looking at treatment-experienced populations -- have traditionally included very small numbers of women, especially in the earliest studies of new antiretroviral agents. We know that there are gender-specific complications associated with HIV disease. However, we do not know a great deal about how gender impacts the efficacy and side effects of HIV medications," said Judith Currier, M.D., Associate Director of the University of California, Los Angeles, Center for Clinical AIDS Research and Education and a lead investigator in the GRACE study.

"The need for an increased focus on women living with HIV/AIDS was a key theme of the recent AIDS 2006 conference in Toronto, Canada. GRACE is an example of the steps that need to be taken to address the evolving HIV epidemic. The development of this trial included extensive collaboration with the HIV community," said Dawn Averitt-Bridge, founder and Chair of the Board of The Well Project. "Women who participate in GRACE will play a very important role in advancing the understanding of HIV treatment in women."

The GRACE study will include approximately 50 sites in the United States, Mexico and Canada, and will seek to enroll approximately 420 participants, 70 percent of whom will be women. Participants must be of 18 years or older, have a viral load of 1000 copies/mL or greater and have previous intolerance or failure to prior therapy consisting of a protease inhibitor and/or non-nucleoside reverse transcriptase inhibitor-based highly active antiretroviral treatment regimen of at least 12 weeks. All participants will receive PREZISTA/rtv (600/100mg twice a day) with an optimized background regimen chosen by the investigator and based on resistance testing and prior treatment history.

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: 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.

Coadministration of PREZISTA/rtv is contraindicated with drugs that are highly dependent on CYP3A for clearance and have a narrow therapeutic index (e.g., astemizole, terfenadine, dihydroergotamine, ergonovine, ergotamine, methylergonovine, cisapride, pimozide, midazolam, or triazolam) and for which elevated plasma concentrations are associated with serious and/or life-threatening events. 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. Failure to correctly administer PREZISTA with ritonavir and food will result in reduced plasma concentration of darunavir that will be insufficient to achieve the desired antiviral 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.

PREZISTA should be used during pregnancy only if the potential benefit justifies the potential risk. There are no adequate and well-controlled studies in pregnant women. The effects of PREZISTA on pregnant women or their unborn babies are not known.

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.
-end-
For additional information on inclusion and exclusion criteria and GRACE study sites, see www.clinicaltrials.gov, call 1-866-512-7943 or email GRACEstudy@wilm.ppdi.com.

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., is commercializing 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.

Edelman Public Relations

Related HIV Articles from Brightsurf:

BEAT-HIV Delaney collaboratory issues recommendations measuring persistent HIV reservoirs
Spearheaded by Wistar scientists, top worldwide HIV researchers from the BEAT-HIV Martin Delaney Collaboratory to Cure HIV-1 Infection by Combination Immunotherapy (BEAT-HIV Collaboratory) compiled the first comprehensive set of recommendations on how to best measure the size of persistent HIV reservoirs during cure-directed clinical studies.

The Lancet HIV: Study suggests a second patient has been cured of HIV
A study of the second HIV patient to undergo successful stem cell transplantation from donors with a HIV-resistant gene, finds that there was no active viral infection in the patient's blood 30 months after they stopped anti-retroviral therapy, according to a case report published in The Lancet HIV journal and presented at CROI (Conference on Retroviruses and Opportunistic Infections).

Children with HIV score below HIV-negative peers in cognitive, motor function tests
Children who acquired HIV in utero or during birth or breastfeeding did not perform as well as their peers who do not have HIV on tests measuring cognitive ability, motor function and attention, according to a report published online today in Clinical Infectious Diseases.

Efforts to end the HIV epidemic must not ignore people already living with HIV
Efforts to prevent new HIV transmissions in the US must be accompanied by addressing HIV-associated comorbidities to improve the health of people already living with HIV, NIH experts assert in the third of a series of JAMA commentaries.

The Lancet HIV: Severe anti-LGBT legislations associated with lower testing and awareness of HIV in African countries
This first systematic review to investigate HIV testing, treatment and viral suppression in men who have sex with men in Africa finds that among the most recent studies (conducted after 2011) only half of men have been tested for HIV in the past 12 months.

The Lancet HIV: Tenfold increase in number of adolescents on HIV treatment in South Africa since 2010, but many still untreated
A new study of more than 700,000 one to 19-year olds being treated for HIV infection suggests a ten-fold increase in the number of adolescents aged 15 to 19 receiving HIV treatment in South Africa, according to results published in The Lancet HIV journal.

Starting HIV treatment in ERs may be key to ending HIV spread worldwide
In a follow-up study conducted in South Africa, Johns Hopkins Medicine researchers say they have evidence that hospital emergency departments (EDs) worldwide may be key strategic settings for curbing the spread of HIV infections in hard-to-reach populations if the EDs jump-start treatment and case management as well as diagnosis of the disease.

NIH HIV experts prioritize research to achieve sustained ART-free HIV remission
Achieving sustained remission of HIV without life-long antiretroviral therapy (ART) is a top HIV research priority, according to a new commentary in JAMA by experts at the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health.

The Lancet HIV: PrEP implementation is associated with a rapid decline in new HIV infections
Study from Australia is the first to evaluate a population-level roll-out of pre-exposure prophylaxis (PrEP) in men who have sex with men.

Researchers date 'hibernating' HIV strains, advancing BC's leadership in HIV cure research
Researchers have developed a novel way for dating 'hibernating' HIV strains, in an advancement for HIV cure research.

Read More: HIV News and HIV Current Events
Brightsurf.com is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com.