ViiV Healthcare Presents New Data from HIV/AIDS Portfolio Demonstrating Research Advances and Commitment to Patient Care at Conference on Retroviruses and Opportunistic Infections

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 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.  

Indication

SELZENTRY, in combination with other antiretroviral agents, is indicated for adult patients infected with only CCR5-tropic HIV-1.  This indication is based on analyses of plasma HIV-1 RNA levels in two controlled studies of SELZENTRY in treatment-experienced patients and one study in treatment-naive patients.  Both studies in treatment-experienced patients were conducted in clinically advanced, 3-class antiretroviral-experienced (NRTI, NNRTI, PI, or enfuvirtide) adults

with evidence of HIV-1 replication despite ongoing antiretroviral therapy.  The following points should be considered when initiating therapy with SELZENTRY:

• Tropism testing must be conducted with a highly sensitive tropism assay that has demonstrated the ability to identify patients appropriate for SELZENTRY use
• Use of SELZENTRY is not recommended in patients with dual/mixed or CXCR4-tropic HIV-1 as efficacy was not demonstrated in a Phase 2 study of this patient group
• The safety and efficacy of SELZENTRY have not been established in pediatric patients
• In treatment-naive patients, more patients treated with SELZENTRY experienced virologic failure and developed lamivudine resistance compared with efavirenz

Important safety considerations for SELZENTRY

WARNING: See full prescribing information for complete boxed warning.  Hepatotoxicity has been reported which may be preceded by evidence of a systemic allergic reaction (e.g., pruritic rash, eosinophilia or elevated IgE).  Immediately evaluate patients with signs or symptoms of hepatitis or allergic reaction.

Liver problems (liver toxicity) have happened in patients taking SELZENTRY.  An allergic reaction may happen before liver problems occur.  Stop taking SELZENTRY and call your doctor right away if you get any of the following symptoms:

• An itchy rash on your body (allergic reaction)
• Your skin or eyes look yellow and/or dark (tea-colored) urine
• Vomiting and/or upper right stomach area (abdominal) pain

SELZENTRY should always be taken in combination with other medicines used to treat HIV.  SELZENTRY does not cure HIV infection or AIDS (acquired immune deficiency syndrome).  The most serious side effects with SELZENTRY include liver problems, heart problems (including heart attack), low blood pressure when standing up, and changes in the immune system.  There may also be possible chance of infection or cancer.  In clinical trials, the most common side effects of SELZENTRY included cough, fever, colds, rash, muscle and joint pain, stomach pain, and dizziness.

SELZENTRY may affect your immune system, and lead to an increased risk of getting other infections or cancer.  The long-term effects of treatment with SELZENTRY are unknown at this time.  You should also talk to your doctor right away if you have any of the following other symptoms:  nausea, fever, flu-like symptoms, or fatigue.

If you have side effects when taking SELZENTRY, you should talk to your doctor right away.  When SELZENTRY has been given with other HIV drugs, there have been serious side effects, including:

• Liver problems
• Heart problems, including heart attack
• Low blood pressure when standing up (postural hypotension).  Low blood pressure when standing up can cause dizziness or fainting.  Do not drive a car or operate machinery if you have dizziness while taking SELZENTRY
• Changes in your immune system.  A condition called immune reconstitution syndrome can occur when taking HIV medicines.  Your immune system could get stronger and begin fighting hidden infections in your body such as pneumonia, herpes virus, or tuberculosis.

Tell your doctor if you develop new symptoms of infection such as cold sores, fever, or blisters after starting your HIV medicines.  

This is a list of the most common side effects of SELZENTRY:

• Cough    
• Muscle and joint pain
• Fever
• Stomach pain
• Colds
• Dizziness
• Rash

These are not all of the side effects of SELZENTRY.  For more information, ask your doctor or pharmacist.  Do not take SELZENTRY if you are allergic to SELZENTRY or any of its ingredients.  Keep your doctor informed about all the medicines you use, including prescription and nonprescription medicines, vitamins, and herbal supplements.  Do not take products that contain St. John's Wort (Hypericum perforatum).  St. John's Wort may lower the levels of SELZENTRY in your blood so that it will not work to treat your CCR5-tropic HIV infection.

SELZENTRY does not cure HIV infection or AIDS, nor does it prevent you from passing HIV on to others.  People taking SELZENTRY may still develop opportunistic infections or other conditions associated with HIV infection.  The long-term effects of SELZENTRY are not known at this time.  For these reasons it is very important that you remain under a doctor's care.

For additional important information about SELZENTRY, please visit www.selzentry.com.

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/FTC–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).

EPZICOM (abacavir/lamivudine) is a once-a-day HIV medication that combines abacavir sulfate and lamivudine in a single tablet and is indicated for the treatment of HIV-1 infection in adults.

Important Information about EPZICOM

EPZICOM, in combination with other antiretroviral agents, is indicated for the treatment of HIV-1 infection in adults.   

EPZICOM is one of 3 medicines containing abacavir.  Before starting EPZICOM, your healthcare professional will review your medical history in order to avoid the use of abacavir if you have experienced an allergic reaction to abacavir in the past.

In one study, more patients had a severe hypersensitivity reaction in the abacavir once-daily group than in the abacavir twice-daily group.   

EPZICOM should not be used as part of a triple-nucleoside regimen.

EPZICOM does not cure HIV infection/AIDS or prevent passing HIV to others.

Important Safety Information

EPZICOM contains abacavir, which is also contained in ZIAGEN® (abacavir sulfate) and TRIZIVIR® (abacavir sulfate, lamivudine, and zidovudine).  Patients taking EPZICOM may have a serious allergic reaction (hypersensitivity reaction) that can cause death. Your risk of this allergic reaction is much higher if you have a gene variation called HLA-B*5701 than if you do not.  Your doctor can determine with a blood test if you have this gene variation.  If you get a symptom from 2 or more of the following groups while taking EPZICOM, call your doctor right away to determine if you should stop taking this medicine.

If you get a symptom from 2 or more of the following groups while taking EPZICOM, stop taking EPZICOM and call your doctor right away:

1. Fever

2. Rash

3. Nausea, vomiting, diarrhea, or abdominal (stomach area) pain

4. Generally ill feeling, extreme tiredness, or achiness

5. Shortness of breath, cough, or sore throat

Carefully read the Warning Card that your pharmacist gives you and carry it with you at all times.

If you stop EPZICOM because of an allergic reaction, NEVER take EPZICOM or any other abacavir-containing medicine (ZIAGEN, TRIZIVIR) again.  If you take EPZICOM or any other abacavir-containing medicine again after you have had an allergic reaction, WITHIN HOURS you may get life-threatening symptoms that may include very low blood pressure or death.

If you stop EPZICOM for any other reason, even for a few days, and you are not allergic to EPZICOM, talk with your healthcare professional before taking it again.  Taking EPZICOM again can cause a serious or life-threatening reaction, even if you never had an allergic reaction before.  If your healthcare professional tells you that you can take EPZICOM again, start taking it when you are around medical help or people who can call a doctor if you need one.

A build-up of lactic acid in the blood and an enlarged liver, including fatal cases, has been reported.

Do not take EPZICOM if your liver does not function normally.

Some patients infected with both hepatitis B virus (HBV) and HIV have worsening of hepatitis after stopping lamivudine (a component of EPZICOM).  Discuss any change in treatment with your doctor.  If you have both HBV and HIV and stop treatment with EPZICOM, you should be closely monitored by your doctor for at least several months.

Worsening of liver disease (sometimes resulting in death) has occurred in patients infected with both HIV and hepatitis C virus who are taking anti-HIV medicines and are also being treated for hepatitis C with interferon with or without ribavirin.  If you are taking EPZICOM as well as interferon with or without ribavirin and you experience side effects, be sure to tell your doctor.

When you start taking HIV medicines, your immune system may get stronger and could begin to fight infections that have been hidden in your body, such as pneumonia, herpes virus, or tuberculosis.  If you have new symptoms after starting your HIV medicines, be sure to tell your doctor.

Changes in body fat may occur in some patients taking antiretroviral therapy.  These changes may include an increased amount of fat in the upper back and neck ("buffalo hump"), breast, and around the trunk.  Loss of fat from the legs, arms, and face may also occur.  The cause and long-term health effects of these conditions are not known at this time.

Some HIV medicines, including those containing abacavir (ZIAGEN, EPZICOM or TRIZIVIR), may increase your risk of heart attack.  If you have heart problems, smoke, or suffer from diseases that increase your risk of heart disease such as high blood pressure, high cholesterol, or diabetes, tell your doctor.

The most common side effects seen with the drugs in EPZICOM dosed once-daily were allergic reaction, trouble sleeping, depression, headache, tiredness, dizziness, nausea, diarrhea, rash, fever, stomach pain, abnormal dreams, and anxiety.  Most of the side effects do not cause people to stop taking EPZICOM.

For additional important information about EPZICOM please visit www.epzicom.com.

For additional important information about ZIAGEN please visit www.treathiv.com

About ViiV Healthcare  

ViiV Healthcare is a global specialist HIV company established by GlaxoSmithKline (NYSE: GSK) and Pfizer (NYSE: PFE) 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.

Cautionary statement regarding forward-looking statements

GlaxoSmithKline disclosure notice: Under the safe harbor provisions of the U.S. Private Securities Litigation Reform Act of 1995, GSK cautions investors that any forward-looking statements or projections made by GSK, including those made in this announcement, are subject to risks and uncertainties that may cause actual results to differ materially from those projected.  Factors that may affect GSK' s operations are described under 'Risk Factors' in the 'Business Review' in the company' s Annual Report on Form 20-F for 2008.

Pfizer disclosure notice: Pfizer assumes no obligation to update any forward-looking statements contained in this release as a result of new information or future events or developments.

This release contains forward-looking information about Pfizer, GlaxoSmithKline and ViiV Healthcare and about the prospects of the companies, including revenues from in-line products and the potential benefits of product candidates that will be contributed to that company, as well as the potential financial impact of the transaction.  Such information involves substantial risks and uncertainties including, among other things, decisions by regulatory authorities regarding whether and when to approve any drug applications that have been or may be filed for such product candidates as well as their decisions regarding labeling and other matters that could affect the availability or commercial potential of such product candidates; and competitive developments.

A further list and description of risks and uncertainties can be found in Pfizer's Annual Report of Form 10-K for the fiscal year ended December 31, 2008 and in its reports on Form 10-Q and Form 8-K.

SOURCE ViiV Healthcare

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