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Head-to-head 96-week study shows EPZICOM® was comparable to Truvada® -- in efficacy and safety measures -- for HIV treatment-naïve patients
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Research Triangle Park, NC, June 23, 2009 - GlaxoSmithKline (NYSE: GSK) announced today that the HEAT (HIV Study with EPZICOM and Truvada) (EPZ104057) clinical trial was published in June 23 issue of AIDS(volume 23, issue 10), the official journal of the International AIDS Society. In this 96-week study, EPZICOM® (abacavir sulfate and lamivudine) provided comparable efficacy to once-daily Truvada® (emtricitabine and tenofovir disoproxil fumarate) and further supports EPZICOM is an effective option for the treatment of HIV.
The data being published were previously presented in part at the 15th Conference on Retroviruses and Opportunistic Infections in February 2008 (48 week data), at the 17th International AIDS Conference in August 2008 (96 week data) and at the 16th Conference on Retroviruses and Opportunistic Infections (CROI) February 2009 (biomarker data).
"The complete data set from the HEAT clinical trial shows the comparison between EPZICOM and Truvada on several important efficacy and safety issues over an extended period," said Judith Ng-Cashin, M.D., Vice President for Infectious Diseases, GlaxoSmithKline. "Results for both medications were comparable in patients with high and low viral load. All patients should work with their physicians to determine the best treatment regimens."
Results of the HEAT Study
HEAT is the first, large, prospective, long-term, head-to-head trial to evaluate the safety and efficacy of EPZICOM and Truvada, both combined with a boosted protease inhibitor (Kaletra) administered once-daily in adults who had no previous exposure to HIV medicines. The study involved 688 HIV therapy-naïve patients: 343 randomized to treatment with EPZICOM and 345 randomized to treatment with Truvada. The primary efficacy endpoint was to determine the proportion of subjects with a viral load of <50 c/mL at 48 weeks and the primary safety endpoint was to evaluate safety and tolerability of both regimens at 96 weeks.
In HEAT, EPZICOM was comparable to Truvada in virologic and immunologic efficacy, regardless of baseline viral load.
· At 48 weeks, 68% of subjects receiving EPZICOM versus 67% of subjects receiving Truvada achieved a viral load <50copies (c)/mL.
· At 96 weeks, 60% of subjects receiving EPZICOM versus 58% of subjects receiving Truvada achieved a viral load <50c/mL.
· Success rates at 96 weeks were similar in both treatment arms among patients who achieved a viral load <50c/mL (ITT, M=F), regardless of baseline viral load (63% of EPZICOM patients vs. 58% of Truvada patients with <100,000c/mL and 56% of EPZICOM patients vs. 58% of Truvada patients with ≥100,000c/mL).
· Median CD4+ increase from baseline was comparable in both arms at week 96 (250 vs. 247).
Overall, both regimens were generally well-tolerated with comparable safety profiles and few study discontinuations due to adverse events (6% for both treatment arms). Virologic failure occurred in 14% of patients in both groups.
Renal Effects Assessed in Both Treatment Arms
Small improvements in the typical markers of kidney function (estimated glomerular filtration rate and creatinine clearance) were observed in both treatment arms. Progression to a more advanced chronic kidney disease stage occurred in 31 patients (10%) receiving EPZICOM and 49 patients (15%) receiving Truvada. Five subjects in the Truvada arm developed proximal renal tubule dysfunction according to predefined criteria compared to zero in the arm containing EPZICOM. Eleven patients receiving Truvada advanced to stage 3 chronic kidney disease as compared to four in the arm containing EPZICOM.
Adverse events were similar in both arms. Both treatment arms had 6% of patients prematurely withdraw due to adverse events. In addition, 15% of patients had drug-related Grade 3-4 adverse events in both treatment arms. Patients receiving EPZICOM reported higher rates of suspected abacavir hypersensitivity reaction compared with Truvada (4% vs. <1%). Prospective HLA-B*5701 screening was not employed in this study. Overall, treatment-limiting adverse events were comparable between the two arms.
Additional Data Regarding EPZICOM and Truvada
A separate study by the AIDS Clinical Trials Group (ACTG A5202) is ongoing and also evaluates the safety and efficacy of EPZICOM and Truvada as HIV treatment backbones. A routine review in February, 2008 of ACTG A5202 by the data safety monitoring board (DSMB) found that although both the EPZICOM and Truvada treatment arms were effective in reducing HIV viral load, a statistically significant higher rate of virologic failure and safety endpoints were seen in patients with high viral loads (as defined at screening) in the treatment arm containing EPZICOM. Therefore, the DSMB recommended un-blinding patients receiving EPZICOM in the high viral load arm and these study participants were allowed to continue on their assigned regimens or switch to an alternative. In patients who entered the study with screening HIV RNA ≥ 100,000 c/mL, the proportion that achieved HIV RNA < 50 c/mL at week 48 was 0.75 for EPZICOM, and 0.80 for Truvada (p=0.2).
About Abacavir and Hypersensitivity
Abacavir sulfate (abacavir) is a nucleoside reverse transcriptase inhibitor with an established safety and efficacy profile in HIV treatment. Abacavir is a component in the GSK products ZIAGEN®, TRIZIVIR® and EPZICOM®. The most significant treatment-limiting event known to occur with abacavir is a hypersensitivity reaction, which occurs in approximately eight percent of patients and usually emerges within the first six weeks of therapy.
Symptoms of a hypersensitivity reaction to abacavir include combinations of at least two of the following: fever, rash, constitutional symptoms, gastrointestinal symptoms and respiratory symptoms that become more severe with continued dosing and may become potentially life-threatening. These symptoms may overlap with adverse events related to other HIV medications and other medical conditions, contributing to difficulty in diagnosis on the basis of symptoms alone.
Results from HLA-B*5701 testing to assess risk for abacavir HSR should never substitute for appropriate clinical vigilance for ABC HSR and patient management in individuals undergoing treatment with abacavir-containing products.
About HLA-B*5701 Screening
HLA-B*5701 screening should be performed in patients without prior abacavir exposure.
It is important to discontinue abacavir permanently if hypersensitivity cannot be ruled out, regardless of the result of the HLA-B*5701 testing.
HLA-B*5701 testing should never be performed to support a decision to re-challenge with abacavir.
HLA-B*5701 screening for the risk of abacavir hypersensitivity should never substitute for appropriate clinical vigilance and patient management in individuals undergoing treatment with abacavir-containing products.
Skin patch testing was a research tool used in this study to detect an immunologic skin reaction to abacavir. Its utility in clinical practice, however, has not been established.
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.
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.
Your risk of this allergic reaction is much higher if you have a gene variation called HLA-B-5701 than if you do not.
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.
Some HIV medicines, including those containing abacavir (ZIAGEN®, EPZICOM®, and TRIZIVIR®), may increase your risk of heart attack.
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 GlaxoSmithKline
GlaxoSmithKline is one of the world's leading research-based pharmaceutical and healthcare companies and an industry leader in HIV research and therapies. The company is engaged in basic research programs designed to investigate new targets to treat HIV. For full information on GSK's HIV medications, please visit www.treatHIV.com.
US Media enquiries: Marc Meachem (919) 483-2839
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