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Long-Term Study Evaluates Boosted PREZISTA(R) Vs. Lopinavir/Ritonavir as Part of HIV Combination Therapy in Treatment-Naive Adults, Tibotec press release
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BRIDGEWATER, N.J., Oct 26, 2008 / from Tibotec
- Ninety-six week ARTEMIS data presented at ICAAC -
Ninety-six week results presented today from a phase 3, randomized, open-label, ongoing clinical trial showed that 79 percent of treatment-naive HIV-1 infected adults taking PREZISTA(R) 800 mg (two 400 mg tablets) with 100 mg ritonavir (r) once daily reached an undetectable viral load (<50 copies/mL) at week 96, compared with 71 percent of patients taking lopinavir/ritonavir 800 mg/200 mg once daily (or 400 mg/100 mg twice daily), each with a fixed dose of emtricitabine and tenofovir disoproxil fumarate.
Results from the study, known as ARTEMIS, were presented today at the 48th Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC) in Washington, DC. ARTEMIS is a 192-week study comparing the efficacy and safety of the protease inhibitors (PIs) PREZISTA/r and lopinavir/r in treatment-naive adults with HIV (those who have never taken HIV medication before). PREZISTA was developed by Tibotec Pharmaceuticals and is marketed in the U.S. by Tibotec Therapeutics, a division of Ortho Biotech Products, L.P.
At 48 weeks, the primary objective of ARTEMIS was reached when PREZISTA/r was demonstrated to be non-inferior to lopinavir/r for virologic response (confirmed HIV RNA < 50 copies/mL). The difference between the treatment arms was not significant at week 48. The pre-planned safety and efficacy analysis at 96 weeks was a secondary endpoint. At 96 weeks, the study showed PREZISTA/r was non-inferior to lopinavir/r for virologic response. The estimated difference in virologic response between the treatment groups was eight percent and was statistically significant (95 percent confidence interval 1.8; 14.7). The 96-week results from ARTEMIS will be submitted to the FDA.
"This study offers the healthcare provider community long-term efficacy and safety data for PREZISTA in treatment-naive adult patients," said Tony Mills, M.D., ARTEMIS clinical investigator.
PREZISTA, co-administered with 100 mg ritonavir (PREZISTA/r), and with other antiretroviral agents, is indicated for the treatment of human immunodeficiency virus (HIV-1) infection.
This indication is based on analyses of plasma HIV RNA levels and CD4+ cell counts from two controlled phase 3 trials of 48 weeks duration in antiretroviral treatment-naive and treatment-experienced patients and two controlled phase 2 trials of 96 weeks duration in clinically advanced, treatment-experienced patients.
In treatment-experienced patients, the following points should be considered when initiating therapy with PREZISTA/r: treatment history and, when available, genotypic or phenotypic testing, should guide the use of PREZISTA/r. The use of other active agents with PREZISTA/r is associated with a greater likelihood of treatment response.
The risks and benefits of PREZISTA/r have not been established in pediatric patients. No clinical studies have demonstrated the effect of PREZISTA/r on clinical progression of HIV-1.
ARTEMIS 96-Week Study Results
In the 96-week per-protocol analysis of 689 patients, PREZISTA/r 800/100 mg once daily was shown to be non-inferior to lopinavir/r 800/200 mg once daily or 400/100 mg twice daily in treatment-naive adults with HIV-1. In addition, in the intent-to-treat analysis, the study showed that:
-- 79 percent of patients in the PREZISTA/r arm reached an undetectable
viral load (<50 copies/mL) vs. 71 percent of patients in the
lopinavir/r arm, (p=0.012).
-- Of patients with baseline viral load greater than and equal to 100,000
copies/mL, 76 percent of patients in the PREZISTA/r arm reached an
undetectable viral load (<50 copies/mL) vs. 63 percent of patients in
the lopinavir/r arm, (p=0.023).
-- Of patients with baseline viral load less than 100,000 copies/mL, 81
percent of patients in the PREZISTA/r arm reached an undetectable viral
load (<50 copies/mL) vs. 75 percent of patients in the lopinavir/r
arm, (p=not significant).
-- Of patients with baseline CD4+ cell count less than 200 cells per cubic
millimeter, 79 percent of patients in the PREZISTA/r arm reached an
undetectable viral load (<50 copies/mL) vs. 65 percent of patients in
the lopinavir/r arm, (p=0.009).
-- Of patients with baseline CD4+ cell count greater than 200 cells per
cubic millimeter, 79 percent of patients in the PREZISTA/r arm reached
an undetectable viral load (<50 copies/mL) vs. 75 percent of patients
in the lopinavir/r arm, (p=not significant).
ARTEMIS Safety Findings
-- Incidence of grade 2-4 treatment-related diarrhea reported in the
PREZISTA/r arm was four percent vs. 11 percent in the lopinavir/r arm.
Nausea was reported in two percent vs. three percent, respectively.
-- In both treatment arms, grade 2-4 treatment-related rash occurred
infrequently; three percent in the PREZISTA/r arm vs. one percent in the
lopinavir/r arm.
-- Discontinuations due to adverse events were four percent in the
PREZISTA/r arm vs. nine percent in the lopinavir/r arm.
Dosing
Recommended dosing for treatment-naive adult patients is 800 mg (two 400 mg tablets) taken with 100 mg ritonavir once daily with food. The new 400 mg tablet will be available by November 1. For treatment-experienced adult patients, the dosing for PREZISTA remains 600 mg taken with 100 mg ritonavir twice daily with food. PREZISTA must be taken in combination with other ARVs. PREZISTA/r is not recommended for use in patients with severe hepatic impairment.
About the ARTEMIS study
ARTEMIS (AntiRetroviral Therapy with TMC114 examined in naive subjects) is an international ongoing, randomized, controlled, open-label non-inferiority phase 3 trial that compares the efficacy and safety of PREZISTA/r with lopinavir/r in treatment-naive HIV-1-infected adult patients with viral load greater than 5,000 copies/mL. Patients were randomized to receive PREZISTA/r 800 mg/100 mg once daily or, based on approved dosing in each country, either lopinavir/r 800 mg/200 mg once daily or 400 mg/100 mg twice daily (n=346), plus a fixed-dose background regimen of tenofovir and emtricitabine once daily. Patient randomization was stratified based on viral load and CD4+ cell count.
The main objective of the study was to demonstrate non-inferiority of PREZISTA/r versus lopinavir/r in proportion of patients achieving virologic response, defined as confirmed HIV RNA <50 copies/mL. Non-inferiority of PREZISTA/r vs. lopinavir/r was defined as a maximum allowable difference of 12 percent for virologic response, with a one-sided significance level of alpha equals to 0.025 and 90 percent power.
Important Safety Information
PREZISTA does not cure HIV infection or AIDS, and does not prevent passing HIV to others.
Coadministration of PREZISTA/r is contraindicated with drugs that are highly dependent on CYP3A for clearance and for which elevated plasma concentrations are associated with serious and/or life-threatening events (e.g., dihydroergotamine, ergonovine, ergotamine, methylergonovine, cisapride, pimozide, oral midazolam, triazolam, lovastatin, or simvastatin).
Coadministration of PREZISTA/r is also contraindicated with rifampin and products containing St. John's wort (Hypericum perforatum) because this may cause significant decrease in plasma concentration of darunavir, resulting in loss of therapeutic effect and development of resistance.
Coadministration is not recommended with indinavir, lopinavir/ritonavir, saquinavir, and pravastatin.
Caution should be used when prescribing agents such as sildenafil, vardenafil, tadalafil, or other substrates, inhibitors, or inducers of CYP3A in patients receiving PREZISTA/r. This list of potential drug interactions is not complete.
PREZISTA must be co-administered with 100 mg ritonavir and food to achieve the desired antiviral effect. Failure to correctly administer PREZISTA with ritonavir and food may result in a loss of efficacy of darunavir. Please refer to ritonavir prescribing information for additional information on precautionary measures.
Drug-induced hepatitis (e.g., acute hepatitis, cytolytic hepatitis) has been reported with PREZISTA/r. During the clinical development program (n=3063), hepatitis has been reported in 0.5 percent of patients receiving combination therapy with PREZISTA/r. Patients with pre-existing liver dysfunction, including chronic active hepatitis B or C, have an increased risk for liver function abnormalities, including severe hepatic adverse events.
Post-marketing cases of liver injury, including some fatalities, have been reported. A causal relationship with PREZISTA/r therapy has not been established.
Appropriate laboratory testing should be conducted prior to initiating therapy with PREZISTA/r and patients should be monitored during treatment. Increased AST/ALT monitoring should be considered in patients with underlying chronic hepatitis, cirrhosis, or in patients who have pre-treatment elevations of transaminases, especially during the first several months of PREZISTA/r treatment. Evidence of new or worsening liver dysfunction (including clinically significant elevation of liver enzymes and/or symptoms such as fatigue, anorexia, nausea, jaundice, dark urine, liver tenderness, hepatomegaly) in patients on PREZISTA/r should prompt consideration of interruption or discontinuation of treatment.
Cases of severe skin rash (0.4 percent) and Stevens-Johnson syndrome (<0.1 percent) have been reported in subjects receiving PREZISTA. In clinical trials (n=3063), rash (all grades, generally mild-to-moderate, regardless of causality) occurred in 10.3 percent of subjects treated with PREZISTA. Discontinuation due to rash was 0.5 percent. 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, hyperglycemia, and increased bleeding in hemophiliacs have been reported in patients receiving protease inhibitors. Initiation or dose adjustments of insulin or oral hypoglycemic agents may be required. A causal relationship between protease inhibitors and these events has not been established.
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/r treated patients.
PREZISTA/r is not recommended for use in patients with severe hepatic impairment. There are no pharmacokinetic or safety data available in patients with severe hepatic impairment.
PREZISTA should be used during pregnancy only if the potential benefit justifies the potential risk. No adequate and well-controlled studies have been conducted in pregnant women.
In treatment-naive adult patients receiving a PREZISTA/r-containing regimen, the most common adverse drug reactions (> or = 2 percent) reported of at least moderate to severe intensity (> or = Grade 2) were diarrhea (6 percent), headache (5 percent), abdominal pain (4 percent), nausea (3 percent), vomiting (2 percent), and rash (2 percent).
In treatment-experienced adult patients receiving a PREZISTA/r-containing regimen, the most common adverse drug reactions (> or = 2 percent) reported of at least moderate to severe intensity (> or = Grade 2) were diarrhea (12 percent), nausea (7 percent), abdominal pain (5 percent), rash (6 percent), vomiting (4 percent), asthenia (3 percent), headache (2 percent), abdominal distension (2 percent), and dyspepsia (2 percent).
This is not a complete list of all adverse drug reactions reported with the use of PREZISTA/r.
Please see full Prescribing Information for more details. A copy of full Prescribing Information can be obtained by visiting PREZISTA.com.
About Tibotec Pharmaceuticals
Tibotec Pharmaceuticals, based in Yardley, Pa., is a pharmaceutical research and development company, with headquarters in Ireland and main research and development operations/labs in Belgium. Tibotec is dedicated to the discovery and development of innovative HIV/AIDS drugs and anti-infectives for diseases of high unmet medical need.
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.
Ortho Biotech Products, L.P. and Tibotec Pharmaceuticals are subsidiaries of Johnson & Johnson.
(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 the Company'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 30, 2007. 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 Johnson & Johnson. The Company does not undertake to update any forward-looking statements as a result of new information or future events or developments.)
Contacts:
Pam Van Houten
Mobile: (908) 295-7367
SOURCE Tibotec Therapeutics
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