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ViiV Presents New Data from HIV Portfolio at CROI

[ViiV is the JV between GSK and PFE that includes IDX899 among its assets (#msg-43254006). Of the info in this PR, only the data pertaining to S/GSK1349572, GSK’s integrase inhibitor, is of interest, IMO. (Selzentry, the entry inhibitor previously owned by PFE, is a commercial dud, and Epzicom, the combination of two GSK nukes from the previous millennium, is a useless relic.) The most notable finding vis-à-vis S/GSK1349572 is that it has activity against HIV strains resistant to the two other integrase inhibitors of consequence: MRK’s Isentress and GILD’s elvitegravir (a component of the ‘Quad’ pill). For IDIX investors, a question to ask is whether GSK might combine S/GSK1349572 and IDX899 in some kind of nuke-sparing cocktail.]

http://finance.yahoo.com/news/ViiV-Healthcare-Presents-New-prnews-522232157.html?x=0&.v=1

›Presentations Include New Data for S/GSK1349572, an Integrase Inhibitor in Clinical Development, SELZENTRY, and EPZICOM

February 22, 2010, 7:00 am

SAN FRANCISCO, Feb. 22 /PRNewswire/ -- 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 Trofileâ„¢ 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.

Highlighted Data on EPZICOM

Final 96-week results were presented from the AIDS Clinical Trials Group (ACTG) study A5202, a blinded, randomized equivalence study comparing abacavir/lamivudine (ABC/3TC) to tenofovir DF/emtricitabine (TDF/FTC) administered with efavirenz (EFV) or atazanavir/ritonavir (ATZ/RTV).

Final 96-week data for low viral load stratum was presented at this CROI:

• Data showed that viral failure rates were lower than expected in both the ABC/3TC and TDF/FTC arms, and there were no demonstrable differences between treatments in time to viral failure in those patients with screening <100,000 copies/mL HIV-1 RNA.

• For the primary safety endpoint (time to first new grade 3/4 sign/symptom or lab toxicity), safety events occurred sooner for ABC/3TC than TDF/FTC with EFV as the 3rd drug but not with ATV/RTV.

• Regimen changes occurred significantly earlier for ABC/3TC than TDF/FTC in the low viral load subgroup, regardless of the third drug used. The difference appeared to be the result of an increased frequency of hypersensitivity reactions in this group. However, it should be noted that this study enrolled subjects prior to the performance of routine HLA-B*5701 testing. HLA-B*5701 is a test that identifies those at higher risk for developing hypersensitivity reactions.

Previously, a Data Safety Monitoring Board (DSMB) recommended unblinding those in high viral load stratum (>100,000 copies/mL HIV-1 RNA) due to a shorter time to viral failure for ABC/3TC than TDF/FTC, although all regimens effectively reduced the amount of virus in most subjects. Patients were allowed to continue on their current regimen or shift to another regimen. A secondary analysis showed the proportion of patients in the high viral load group with HIV RNA <50 c/mL at week 48 was 75 percent for the arm containing ABC/3TC and 80 percent for the TDF/FTC arm [(p=0.2), intent-to-treat analysis, switch included].

Results also were reported from ACTG 5224, a substudy of ACTG 5202 examining the long-term effects of ABC/3TC compared to TDF/FTC, combined with either EFV or ATV/RTV, on bone mineral density (BMD) and limb fat in HIV infected treatment-naive patients. Primary endpoints included DEXA-measured changes in lumbar spine and hip BMD and the presence of lipoatrophy at 96 weeks. DEXA, or dual X-ray absorptiometry, is a screening tool used to measure body composition.

Compared to ABC/3TC, TDF/FTC-treated patients had statistically significant larger declines in lumbar spine and hip BMD. Both ABC/3TC- and TDF/FTCâ?“based regimens increased limb fat at 96 weeks, with similar proportion of patients with lipoatrophy. No statistically significant differences were seen in percent change in limb fat between the NRTI arms by intent-to-treat or as-treated analyses.

BMD results:

• At 96 weeks, the mean percent change from baseline in lumbar spine BMD was -1.3 percent for ABC/3TC compared to -3.3 percent for TDF/FTC (p=0.004). The mean percent change from baseline in hip BMD was -2.6 percent for ABC/3TC compared to -3.9 percent for TDF/FTC (p=0.025).

• At 96 weeks, the mean percent change from baseline in lumbar spine BMD was -1.7 percent for EFV compared to -3.2 percent for ATV/RTV (p=0.035). The mean percent change from baseline in hip BMD was -3.1 percent for EFV compared to -3.4 percent for ATV/RTV (p=0.59).

• ATV/RTV led to more significant losses in lumbar spine BMD than EFV. Overall, 5.6 percent of subjects had greater than or equal to 1 fracture (all traumatic), with no significant differences in fracture rates between the NRTI arms (p=1.0), or between EFV vs. ATV/RTV arms (p=0.29).

About ViiV Healthcare

ViiV Healthcare is a global specialist HIV company established by GlaxoSmithKline (NYSE:GSK - News) and Pfizer (NYSE:PFE - News) to deliver advances in treatment and care for people living with HIV. Our aim is to take a deeper and broader interest in HIV/AIDS than any company has done before and take a new approach to deliver effective and new HIV medicines as well as support communities affected by HIV.

GSK holds an 85 percent interest in the ViiV Healthcare and Pfizer holds 15 percent. GSK and Pfizer announced that they had agreed to form a new specialist HIV company on April 16, 2009. The transaction was completed on October 30, 2009. ViiV Healthcare launched on November 3, 2009. For more information on the company, its management, portfolio, pipeline and commitment, please visit www.viivhealthcare.com.‹