Data Analysis of Up to Four Years of Treatment Presented at ICAAC/IDSA 2008 Annual Meeting
WASHINGTON, Oct. 26 /PRNewswire-FirstCall/ -- Schering-Plough Corporation (NYSE: SGP) today reported a data analysis showing that vicriviroc, its investigational CCR5 receptor antagonist, demonstrated sustained viral suppression and increased CD4 cell counts and was well tolerated through up to four years of therapy in treatment-experienced HIV-infected patients. Vicriviroc was administered once-daily as a single tablet in combination with an optimized antiretroviral regimen containing a ritonavir-boosted protease inhibitor. These results represent the longest treatment duration and clinical experience reported to date for a CCR5 receptor antagonist.
Vicriviroc, currently in Phase III development, is an extracellular inhibitor of HIV infection designed to prevent the virus from infecting the immune system's CD4 cells by blocking the CCR5 co-receptor. Approximately 50-60 percent of treatment-experienced patients have virus that uses the CCR5 co-receptor.(1)
Researchers presented the data at the joint Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC) and Infectious Diseases Society of America (IDSA) annual meeting.(2)
The pooled data analysis involved 205 treatment-experienced HIV-infected patients from two vicriviroc Phase II studies who continued on vicriviroc at the completion of 48 weeks of treatment in an open-label extension for each study. Patients received vicriviroc for up to 216 weeks of total treatment duration as part of an optimized antiretroviral regimen.
This analysis showed that vicriviroc was well tolerated overall, with patients developing few complications of HIV disease. Adverse events observed were consistent with expectations for the treatment-experienced HIV-infected population. Importantly, the incidence of malignancy seen across the vicriviroc clinical program has not increased over time even as the cumulative exposure to vicriviroc has increased by numbers of patients and duration of treatment.
"These long-term results demonstrate that vicriviroc added to an optimized background therapy may provide durable viral suppression and sustained elevated CD4 counts in treatment-experienced HIV-infected patients," said Jihad Slim, M.D., division of infectious diseases, Saint Michael's Medical Center, Newark, N.J., and an investigator for the vicriviroc clinical program. "Importantly, vicriviroc was well tolerated, with some patients continuing on treatment for up to four years, and it was not associated with increased liver, CNS or cardiovascular adverse events or with an increased incidence of malignancy in this patient population."
About the Data Analysis
Patients enrolled in the Phase II vicriviroc VICTOR-E1 study(3) (including patients in the placebo arm) and the ACTG 5211 study(4) were eligible to continue on open-label vicriviroc with optimized background therapy at the completion of 48 weeks of treatment in an extension for each study. The vicriviroc dose for all patients was escalated to 30 mg once daily during the open-label treatment period. As there were no dose-related differences in the safety profile, data for all patients receiving vicriviroc were pooled for analysis regardless of the original starting vicriviroc dose. The mean duration of vicriviroc treatment for all patients (N=205) was 96 weeks (range 1-216 weeks).
Analyses were performed on data from all patients who completed at least 12 weeks of vicriviroc treatment (N=196). Virologic response to regimens containing vicriviroc was evidenced within 12 weeks by a significant decrease in virus (HIV RNA) detectable in the blood and was sustained long-term. Median change from baseline viral load (HIV RNA) was -2.1, -2.2, -2.3, -2.3 (log10) at weeks 48, 96, 144 and 168, respectively. Mean change from baseline CD4 (cells/microliter) count was +121, +144, +158 and +143 at the same time points.
Key Safety Findings
Safety analyses were performed on data from all patients who received any vicriviroc treatment (N=205). AIDS-associated opportunistic infections and conditions were observed infrequently and sporadically. Infections involving the upper and lower respiratory tract were the only other infections or adverse events that occurred in 5 percent or more of patients. Elevations of liver enzymes and bilirubin were noted, but were not characteristic of drug-induced liver injury and were judged to be not related to vicriviroc. These infections and other adverse events observed in these patients were generally consistent with expectations for patients with advanced HIV infection and with the multiple drugs being administered.
Status of Vicriviroc Phase III Studies in Treatment-Experienced Patients
Schering-Plough has completed patient enrollment in two large Phase III clinical studies, known as VICTOR-E3 and VICTOR-E4 (Vicriviroc in Combination Treatment with an Optimized Antiretroviral Therapy Regimen in HIV-Infected Treatment-Experienced Subjects), evaluating vicriviroc 30 mg once daily in combination with an optimized background antiretroviral regimen containing a ritonavir-boosted protease inhibitor compared to a control group receiving new optimized background therapy alone. The optimized background therapy must include at least two drugs to which the patient's HIV is susceptible. Patients coinfected with hepatitis B or C may be included in these studies and there are few exclusions of commonly prescribed drugs or need for dose adjustments based on the known vicriviroc drug-drug interaction profile. The two studies involve a total of more than 850 patients and are currently ongoing at more than 160 sites in North America, Latin America, Europe and South Africa.
For more information about the VICTOR-E3 and VICTOR-E4 clinical studies, please visit www.clinicaltrials.gov, search term: vicriviroc.
Status of Vicriviroc Phase II Study in Treatment-Naive Patients
Schering-Plough also has completed patient enrollment in the first part of an ongoing Phase II study of vicriviroc in a novel nucleoside-sparing regimen for first-line therapy of adult treatment-naive HIV-infected patients with R5-tropic virus only. Approximately 80-90 percent of treatment-naive patients have virus that uses the CCR5 co-receptor.(5) The study evaluates vicriviroc 30 mg once-daily in combination with ritonavir-boosted atazanavir,(6) compared to a control group receiving Truvada (emtricitabine and tenofovir disoproxil fumarate)(7) plus ritonavir-boosted atazanavir, which is a currently recommended option for first-line therapy. This novel nucleoside-sparing vicriviroc regimen is designed to help avoid the risk of toxicities associated with the nucleoside class of HIV drugs, which can include neuropathy, myopathy, renal toxicity, hepatic steatosis, lactic acidosis, bone marrow suppression, fat atrophy and, with certain agents, increased risk of myocardial infarction.(8-10) This approach represents a potential opportunity to preserve nucleoside and non-nucleoside reverse transcriptase inhibitors (NRTIs, NNRTIs), integrase inhibitors, fusion inhibitors and most protease inhibitors for later lines of HIV treatment. The full study will involve approximately 200 patients and is ongoing at more than 20 sites in North America, Central America, Europe and South Africa.
For more information about the study, please visit www.clinicaltrials.gov, search term: vicriviroc.
Schering-Plough is an innovation-driven, science-centered global health care company. Through its own biopharmaceutical research and collaborations with partners, Schering-Plough creates therapies that help save and improve lives around the world. The company applies its research-and-development platform to human prescription and consumer products as well as to animal health products. Schering-Plough's vision is to "Earn Trust, Every Day" with the doctors, patients, customers and other stakeholders served by its colleagues around the world. The company is based in Kenilworth, N.J., USA, and its Web site is www.schering-plough.com.
SCHERING-PLOUGH DISCLOSURE NOTICE: The information in this press release includes certain "forward-looking statements" within the meaning of the Private Securities Litigation Reform Act of 1995, including statements relating to the clinical development of and the potential market for vicriviroc. Forward-looking statements relate to expectations or forecasts of future events. Schering-Plough does not assume the obligation to update any forward-looking statement. Many factors could cause actual results to differ materially from Schering-Plough's forward-looking statements, including market forces, economic factors, product availability, patent and other intellectual property protection, current and future branded, generic or over-the-counter competition, the regulatory process, and any developments following regulatory approval, among other uncertainties. For further details of these and other risks and uncertainties that may impact forward-looking statements, see Schering-Plough's Securities and Exchange Commission filings, including Item 8.01 of the company's 8-K filed Oct. 21, 2008.
(1) Coakley E, et al. Second International Workshop Targeting HIV Entry. Oct. 20-21, 2006; Boston, MA, USA; No. 8.
(2) Dunkle LM, Greaves WL, et al. Long-Term Safety of Vicriviroc. 48th Annual Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC)/Infectious Diseases Society of America (IDSA) 46 Annual Meeting; Oct. 25-28, 2008; Washington, D.C., USA; No. H-1269.
(3) Zingman B, Suleiman J, DeJesus E, et al. Vicriviroc, a next generation CCR5 antagonist, exhibits potent, sustained suppression of viral replication in treatment-experienced adults: VICTOR-E1 48-week results. 15th Conference on Retroviruses and Opportunistic Infections (CROI); Feb. 3-6, 2008; Boston, MA, USA; Abstract 39LB.
(4) Gulick RM, Su Z, Flexner C, et al. Phase 2 Study of the safety and efficacy of vicriviroc, a CCR5 inhibitor, in HIV-1-infected, treatment-experienced patients: AIDS Clinical Trials Group 5211. J Infect Dis. 2007;196:304-312.
(5) Hoffmann C (2007) The epidemiology of HIV coreceptor tropism. Eur J Med Res (2007) 12: 385-390.
(6) Atazanavir sulfate is a Bristol-Myers Squibb Company prescription medicine. Please see the atazanavir product insert for information on this product.
(7) Truvada is a registered trademark of Gilead Sciences, Inc. Please see the Truvada product insert for information on this product.
(8) Data collection on adverse events of anti-HIV drugs (DAD) study group. Combination antiretroviral therapy and the risk of myocardial infarction. N Engl J Med 2003; 349: 1993-2003.
(9) The DAD study group. Class of antiretroviral drugs and the risk of myocardial infarction. N Engl J Med 2007; 356: 1723-35.
(10) The DAD study group. Use of nucleoside reverse transcriptase inhibitors and risk of myocardial infarction in HIV-infected patients enrolled in the DAD study: a multi-cohort collaboration. www.thelancet.com published online April 2, 2008, DOI:10.1016/S0140-6736(08)60423-7.
SOURCE Schering-Plough Corporation