At the 17th Conference on Retroviruses and Opportunistic Infections (CROI), ViiV Healthcare presented new data across its broad range of investigational and current medicines for the treatment of HIV/AIDS. Highlighted data at the conference included an oral presentation on the investigational integrase inhibitor, S/GSK1349572, as well as data presentations on SELZENTRY® (maraviroc) and EPZICOM® (abacavir/lamivudine).
"ViiV Healthcare is dedicated to the pursuit of new scientific insights that could help solve complex treatment issues for HIV. We hope that our findings on both our investigational compounds and our available medicines will further enable treatments to be better tailored to the individual patient," stated Dr. Dominique Limet, chief executive officer of ViiV Healthcare. "Beyond currently available therapies, there remains a substantial need for new and effective treatment options. We are committed to advancing S/GSK1349572, as integrase inhibitors represent an important new class of medications for treating patients with HIV."
Overall, more than 24 abstracts were presented during the conference relating to ViiV Healthcare's current medicines and pipeline. These presentations underscore the company's commitment to enhancing its knowledge base for its current medicines, tackling major challenges in treating HIV/AIDS, and providing patients and physicians with data that can lead to more informed prescribing decisions. Highlights from the presentations on S/GSK1349572, SELZENTRY, and EPZICOM are described below.
Data Presentations on S/GSK1349572
An oral presentation described the innovative and rational design approach that led to the identification of a potent series of HIV-1 integrase inhibitors, including the lead clinical candidate, S/GSK1349572. In vitro studies of S/GSK1349572 across a range of subtypes suggest that S/GSK1349572 displays potent antiviral activity to wild type-virus and key integrase inhibitor-resistant HIV. S/GSK1349572 was additive or synergistic, with no observed antagonism of antiviral activity with approved drugs from all classes. The preclinical attributes were confirmed in a Phase IIa study during which HIV-infected subjects receiving S/GSK1349572 50mg alone once daily for 10 days had a mean reduction in HIV-1 of 2.5 log10 c/mL.
In vitro data presented on the resistance profile of S/GSK1349572 suggest that S/GSK1349572 demonstrates activity against site-directed molecular clones generated primarily based on raltegravir (RAL) and elvitegravir (ELV) resistant viruses observed in clinical trials. These data suggest that S/GSK1349572 has a resistance profile distinct from raltegravir and elvitegravir. ViiV Healthcare continues to characterize the resistance profile of S/GSK1349572 in clinical studies.
Additionally, data from a Phase I study suggest that S/GSK1349572 administered in combination with atazanavir (ATV) or ATV/ritonavir (RTV) results in S/GSK1349572 exposure levels that do not require dose adjustment and was generally well tolerated in healthy adult subjects. No clinically significant trends in laboratory values, vital signs, or electrocardiograms (ECGs) were observed during study drug dosing. All adverse events (AEs) were mild or moderate, and no subject withdrew from the study due to an AE. The most common drug related AE observed during treatment with S/GSK1349572 alone was nausea (2/24, 8 percent). The most common AE during concomitant therapy was ocular icterus (11/24, 46 percent). Increased bilirubin was observed only during concomitant ATV dosing. Co-administration with ATV or ATV/RTV increased plasma S/GSK1349572 exposure with a more prominent effect from ATV alone.
Further study is necessary to determine conclusively the efficacy, safety, and resistance profile of S/GSK1349572. Phase IIb studies of S/GSK1349572 are currently progressing as planned. ViiV Healthcare expects to begin the Phase III studies by the end of 2010. S/GSK1349572 was jointly discovered by Shionogi & Co., Ltd. and GlaxoSmithKline, and is being developed by ViiV Healthcare and Shionogi & Co., Ltd.
Highlighted Data on SELZENTRY
Several retrospective analyses in both treatment experienced and naive patients were presented evaluating additional approaches for determining tropism and virologic response to maraviroc, including the following:
- A genotypic analysis of 704 pre-treatment samples from patients in the MERIT study who received maraviroc and had a known virologic outcome using population-based sequencing of the V3 loop, which identified 11R residue as a marker of CXCR4 use.
- An analysis of data from the MERIT study using population-based sequencing of the V3 loop, in which approximately 8 percent of patients screened as R5 by the original Trofile™ assay were classified as X4 by V3 sequencing and 193/283 (68 percent) classified as R5 by both the enhanced sensitivity Trofile and population-based V3 sequencing had week 48 virologic response (<50 copies/mL) on maraviroc.
- An analysis of data from MERIT, MOTIVATE-1, MOTIVATE-2 and A4001029 studies using "deep" gp120 V3-loop sequencing, in which deep sequence discriminated between responders and non-responders regardless of treatment experience and excluded fewer treatment-naive patients in MERIT as non-R5 than the enhanced sensitivity Trofile assay (ESTA) while maintaining comparable performance (223/312 (71 percent)) for deep sequencing compared to 216/299 (72 percent) for ESTA.
- An analysis of data from 31 patients with persistent viremia <50 copies/mL for greater than or equal to 1 year after first line antiretroviral treatment initiation (without a CCR5 antagonist) comparing the ability of different tropism assays to detect X4 viruses, which showed close agreement between V3 quantitative deep sequencing and the enhanced sensitivity Trofile assay.
Collectively, these data suggest population-based genotyping may be a viable alternative to available phenotypic tests in identifying tropism and predicting response to maraviroc.
SELZENTRY® (maraviroc) is a first-in-class oral CCR5 entry inhibitor approved in the U.S. for both treatment-naive and treatment-experienced adult patients with CCR5-tropic HIV-1 virus in combination with other anti-HIV medicines. SELZENTRY is known as Celsentri® outside of the U.S. where it is indicated for appropriate treatment-experienced patients. Use of SELZENTRY in patients with dual/mixed or CXCR4-tropic HIV-1 is not recommended. SELZENTRY will not cure HIV infection.
SOURCE ViiV Healthcare