Phase 1/ 2 Data Presented on Experimental Integrase Inhibitor GS 9137 from Gilead Sciences

Integrase inhibitors are a new class of anti-HIV drugs that block HIV replication by preventing the virus from integrating into the genetic material of human immune cells. Successful development of this new drug class is viewed as critical to the field of HIV therapeutics due to the increasing number of HIV treatment-experienced patients who have exhausted other available options for anti-HIV therapy.

This week at the 13th Conference on Retroviruses and Opportunistic Infections (13^th CROI) in Denver, CO, Edwin DeJesus, MD, of the Orlando Immunology Center in Orlando, FL presented results of a Phase 1/ 2 dose-escalation study of GS 9137, an experimental oral HIV Integrase inhibitor.

This was a double-blind, randomized, placebo-controlled monotherapy study to evaluate the safety, tolerability and antiviral activity of GS 9137 in HIV-infected treatment-naive and treatment-experienced patients. The results are promising, and included significant reductions in viral load in patients using GS 9137 monotherapy and in combination with ritonavir as a boosting agent, compared to placebo.

About the Study

Following is a description of the study methods and results provided in an announcement from Gilead Sciences:

Forty patients were randomized and received one of five doses of GS 9137 (n=30) or placebo (n=10) with food for 10 days. The study evaluated GS 9137 at 200 mg twice daily (BID) (n=6), 400 mg BID (n=6), 800 mg BID (n=6), 800 mg once daily (QD) (n=6), and 50 mg boosted with 100 mg ritonavir QD (n=6).

At study entry, patients were not receiving antiretroviral therapy, had HIV RNA (viral load) between 10,000 and 300,000 copies/mL and CD4 cell count greater than or equal to 200 cells/μL. At baseline, study participants had a mean viral load of 4.75 log10 copies/mL and mean CD4 cell count of 442 cells/microliter. The primary efficacy endpoint was the maximum reduction in viral load from baseline.

GS 9137 monotherapy demonstrated significant antiviral activity compared to placebo (p<0.0001) at all doses.

Median changes in viral load for all doses and adverse events appear in the following charts.

There were no discontinuations or serious adverse events in groups receiving GS 9137. All adverse events were grade 1/ 2 in severity, resolved while on treatment and were not associated with GS 9137 dosing.

A larger and longer-term Phase 2 study is planned to further evaluate the safety and efficacy of this new agent, according to Norbert Bischofberger, PhD, Executive Vice President, Research and Development, Gilead Sciences.

About GS 9137

GS 9137, also known as JTK-303, was licensed by Gilead from Japan Tobacco (JT) in March 2005. Under the terms of the company's agreement with JT, Gilead has exclusive rights to develop and commercialize GS 9137 in all countries of the world, excluding Japan where JT will retain rights.

GS 9137 has been previously evaluated in a Phase I study in Japan to assess pharmacokinetics and safety in healthy volunteers. Data from preclinical and Phase I studies by Japan Tobacco describing the compound’s human pharmacokinetics and safety profile were also presented this week. As an investigational compound, GS 9137 has not yet been determined safe or efficacious in humans for its ultimate intended use.

02/10/06

Source
Gilead Sciences. GILEAD ANNOUNCES RESULTS FROM PHASE I/II STUDY OF INVESTIGATIONAL HIV INTEGRASE INHIBITOR GS 9137. Press Release. February 9, 2006.

Reference
E DeJesus and others. The HIV Integrase Inhibitor GS-9137 (JTK-303) Exhibits Potent Antiviral Activity in Treatment-Naïve and Experienced Patients. 13^th Conference on Retroviruses and Opportunistic Infections. Denver, CO. February 5-8, 2006. Abstract J-1011, Late Breaker 160LB.