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GlaxoSmithKline statement in response to D:A:D Data on Abacavir

Philadelphia, PA  March 27, 2008 - GlaxoSmithKline [NYSE:GSK] has been notified by the Data Collection on Adverse Events of Anti-HIV Drugs (D:A:D) group that new data from an observational database suggests a possible association between anti-retroviral therapy (ART) regimens that contain abacavir and an increased risk of heart attack.  Conversely, analyses of GlaxoSmithKline data show no increased risk of heart attack associated with abacavir.

Accumulated data was sufficient for the D:A:D to analyze five commonly used nucleoside reverse transcriptase inhibitors (NRTIs): zidovudine, didanosine, stavudine, lamivudine and abacavir.  The D:A:D findings of increased risk of heart attack with abacavir are unexpected, as there appears to be no biological reason in the way abacavir works that would explain these findings.  In fact, abacavir has often been chosen due to its favorable lipid and glucose profile.

However, GlaxoSmithKline takes this information seriously, and continues to work with the D:A:D group to ensure that physicians, patients and appropriate regulatory agencies understand this information in order to make the most appropriate treatment decisions for their patients. 

In an announcement today, the FDA stated that they currently believe the analyses conducted with the D:A:D Study data are incomplete.  The FDA is considering, but has not reached a conclusion as to whether this information warrants any regulatory action. The FDA intends to update their communications when additional information or analyses become available.

D:A:D database findings

The D:A:D data indicate that patients who have received abacavir in the most recent 6 months appear to have an increased relative risk for myocardial infarction of 1.9.  Overall this is an uncommon event: 6.1 events/1000 patient years among patients who had taken abacavir in the last 6 months versus 2.6 events/1000 patient years for those who had not (a difference of 3.5 events per 1000 patient years). By comparison to this doubling of relative risk, smoking can increase a person’s risk of heart attack by two or three times, while high cholesterol can increase the risk of heart attack up to six times.  As the D:A:D position paper states, for patients who smoke: ”…stopping smoking would do more to reduce the risk of having a heart attack and other serious diseases more than by stopping abacavir:”

GlaxoSmithKline has analyzed the company’s internal databases, which include information from external post marketing surveillance reports and data from 54 clinical trials with more than 14,000 patients, over 9,600 of whom were on abacavir. The analyses of GlaxoSmithKline data show no increased risk of heart attack associated with abacavir.  In addition, GlaxoSmithKline is not aware of any confirmed increased risk of heart attack with abacavir in the published literature.

The D:A:D presented its data in a poster session at the Conference on Retroviruses and Opportunistic Infections (CROI), on February 4, 2008, in Boston, MA. The D:A:D position statement and other information is available at http://www.cphiv.dk/

Implications for managing HIV

The analysis of the D:A:D database is complex, and the D:A:D group has stated that potential confounding factors cannot be entirely excluded, though the analysis has sought to adjust for a number of variables.  The D:A:D group has stated that these results are therefore not sufficient to prove what causes the increased risk. 

In a pooled analysis of 54 clinical trials no excess risk of myocardial infarction was observed with abacavir use.  No biological mechanism linking abacavir treatment with myocardial infarction has so far been identified.  GlaxoSmithKline believes that in totality, the data on the association of myocardial infarction with abacavir treatment are inconclusive at this time. 

HIV is a serious, life-threatening disease, and a number of factors go into choosing the right therapy.  Therefore, GlaxoSmithKline believes that:

  • Patients should NOT discontinue treatment on their own.
  • Although the D:A:D study data suggest a relative risk increase in heart attack risk for patients who are starting or continuing abacavir, that risk remains low in absolute terms, and therefore abacavir remains an important treatment option for those patients.
  • The total patient profile including comorbidities, concomitant medications, previous retroviral experience, as well as the underlying risk of coronary heart disease should be considered when prescribing HIV antiretroviral therapy, including abacavir. Action should be taken to minimize modifiable cardiovascular risk factors in all patients (e.g. hypertension, hyperlipidemia, diabetes mellitus and smoking) in line with current guidelines.


About HAART therapy

Highly Active Anti-Retroviral Therapy (HAART) has revolutionized HIV treatment and dramatically extended the lifespan of HIV patients.  The NRTI class, including abacavir, remains a cornerstone of HIV therapy; approximately 25% of HIV patients on HAART take abacavir as a proven medicine effective in treating HIV.  For patients who have failed previous therapy, abacavir may be an essential part of treatment.

As with all medicines, physicians and patients must weigh the risks of the disease against the risks and benefits of the medicines available to treat it.  Certain risks may be able to be managed as part of standard HIV patient care.

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.

 

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 a patient gets a symptom from 2 or more of the following groups while taking EPZICOM, the patient must stop taking EPZICOM call his or her 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 a patient stops taking EPZICOM because of an allergic reaction, the patient must NEVER take EPZICOM or any other abacavir-containing medicine (ZIAGEN, TRIZIVIR) again. If a patient takes EPZICOM or any other abacavir-containing medicine again after having had an allergic reaction, WITHIN HOURS the patient may get life-threatening symptoms that may include very low blood pressure or death.

If a patient stops EPZICOM for any other reason, even for a few days, and is not allergic to EPZICOM, the patient should talk with his or her healthcare professional before taking it again. Taking EPZICOM again can cause a serious or life-threatening reaction, even if the patient has never had an allergic reaction before. If the healthcare professional tells the patient that he or she can take EPZICOM again, the patient should start taking it when around medical help or people who can call a doctor if one is needed.

A buildup of lactic acid in the blood and an enlarged liver, including fatal cases, have been reported.

A patient must not take EPZICOM if the 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). Patients should discuss any change in treatment with his or her doctor. If a patient has both HBV and HIV and stops treatment with EPZICOM, the patient should be closely monitored by a 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 a patient is taking EPZICOM as well as interferon with or without ribavirin and experiences side effects, the patient should be sure to tell his or her doctor.

When a patient starts taking HIV medicines, the patient’s immune system may get stronger and could begin to fight infections that have been hidden in the body, such as pneumonia, herpes virus, or tuberculosis. If a patient has new symptoms after starting HIV medicines, the patient should be sure to tell his or her 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.

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

Inquiries

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