Not for distribution to US media

 

Issued – Monday 25 June 2007, London, UK

GlaxoSmithKline announced today that the Committee for Medicinal Products for Human Use (CHMP) issued a positive opinion for the once-daily anticoagulant Arixtra^® 2.5mg (fondaparinux sodium) for the treatment of patients with acute coronary syndromes (ACS) ¹. ACS conditions include chest pain (unstable angina) and two specific types of heart attacks (NSTEMI* and STEMI**).

“We are delighted that the CHMP has given a positive opinion for fondaparinux in the setting of acute coronary syndrome,” says Dr. Lawson Macartney, Senior Vice-President, Cardiovascular and Metabolic Medicine Development Centre, GlaxoSmithKline. “Fondaparinux has the potential to help ACS patients manage their condition and lead potentially longer lives.”

The CHMP reviewed two large pivotal Phase III trials including more than 32,000 patients (OASIS 5 and 6) that evaluated fondaparinux for the treatment of a wide range of patients with ACS.^2,3

UA/NSTEMI

Fondaparinux has received a positive opinion for the treatment of unstable angina or non-ST segment elevation myocardial infarction (UA/NSTEMI) in patients for whom urgent (<120 minutes) invasive management (PCI) is not indicated.

The newly published European Society of Cardiology guideline recommendations are in line with this positive opinion for UA/NSTEMI patients and have given fondaparinux the highest (grade 1A) recommendation for the use in patients receiving either early invasive (<72 hours) or conservative management⁴.

Data from OASIS 5, one of the largest clinical trials ever conducted in patients with acute coronary syndromes (ACS), showed that fondaparinux is as effective as enoxaparin in patients suffering unstable angina and non-ST elevation myocardial infarction, but associated with a lower risk of bleeding and a mortality benefit.

The OASIS 5 clinical trial compared fondaparinux 2.5mg once daily to enoxaparin*** 1mg/kg twice daily in patients with unstable angina/NSTEMI.² Results from the OASIS 5 study showed fondaparinuxwas associated with a 48% (p< 0.001) reduction in major bleeding vs. enoxaparin(2.2% and 4.1% incidence, respectively) up to 9 days. The study also showed that fondaparinux significantly reduces mortality compared to enoxaparin at one month (p=0.02). Mortality rates at one month were 2.9 % in the patient group receiving fondaparinux and 3.5% in the patient group receiving enoxaparin, representing a 17% reduction (p=0.02) in favour of fondaparinux.

STEMI

Fondaparinux has received a positive opinion for the treatment of ST segment elevation myocardial infarction (STEMI) in patients who are managed with thrombolytics or who initially are to receive no other form of reperfusion therapy.

Data from OASIS 6, one of the largest clinical trials conducted in patients with ST elevation myocardial infarction (STEMI) showed that fondaparinux is more effective than standard therapy and that this improved efficacy was achieved with no increased risk of bleeding compared to standard therapies.

OASIS 6 compared fondaparinux to standard therapies (unfractionated heparin or placebo) in STEMI patients.⁴ The overall results of the OASIS 6 study demonstrated superiority of fondaparinux to standard therapy (unfractionated heparin or placebo) in reducing risk of death or recurrent heart attack (risk reduction of 14% at day 30, p=0.008).³

Acute coronary syndromes

ACS affects approximately 3 million people and leads to about 2.5 million hospital admissions worldwide.^5,6 People with ACS have an increased immediate and long-term risk of recurrent heart attack and cardiac death.⁷

About fondaparinux

Fondaparinux is the first in a class of antithrombotics that selectively inhibits Factor Xa, a central protein in the coagulation process. In the treatment of thrombosis, Factor Xa plays a central role in the generation of thrombin, a protein in blood that facilitates blood clotting.

Fondaparinux is approved for use in the European Union (EU) for the prevention of venous thromboembolism (VTE) in patients undergoing surgery for hip fracture (including extended prophylaxis), major knee surgery, and hip replacement; and in acutely ill medical patients who are immobilised and patients undergoing abdominal surgery who are considered at high risk of thromboembolic complications. Additionally, fondaparinux is indicated in the EU for the treatment of acute DVT and the treatment of acute PE, except in haemodynamically unstable patients or patients who require thrombolysis or pulmonary embolectomy.

Important safety information

Contraindications:

Fondaparinux is contraindicated in patients with severe renal impairment, active major bleeding, bacterial endocarditis, and patients with hypersensitivity to fondaparinux sodium.

Warnings:

When epidural/spinal anesthesia or spinal puncture is employed, patients anticoagulated with low–molecular-weight heparins, heparinoids or fondaparinux sodium are at risk of developing an epidural or spinal haematoma, which can result in long-term or permanent paralysis. The risk of these events may be higher with postoperative use of indwelling epidural catheters or concomitant use of drugs affecting haemostasis. Spinal/epidural anesthesia should not be used concurrently with fondaparinuxfor the treatment of VTE.

Fondaparinuxis not intended for intramuscular administration.

Fondaparinux should be used with caution in all patient groups with increased risk of bleeding. This includes the elderly, and patients with moderate renal or severe hepatic impairment. Fondaparinux should be used with caution in those patients weighing less than 50kg (less than 110lbs). Fondaparinux should not be co-administered with drugs that may increase the risk of bleeding.

The efficacy and safety of fondaparinux in patients with heparin-induced thrombocytopenia type II has not been studied. Thrombocytopenia can occur during a treatment with fondaparinux and if the platelet count falls below 100,000/mm³, fondaparinux should be discontinued.

In STEMI patients undergoing primary PCI and in UA/NSTEMI patients undergoing urgent PCI, the use of fondaparinux prior to and during PCI is not recommended. The use of fondaparinux as the sole anticoagulant during PCI is not recommended, therefore UFH should be used according to local practice. There are limited data on the use of UFH during non-primary PCI in patients treated with fondaparinux.

Clinical trials have shown a low but increased risk of guiding catheter thrombus in patients treated with fondaparinux for anticoagulation during PCI compared to control.

About GlaxoSmithKline

GlaxoSmithKline – one of the world's leading research-based pharmaceutical and healthcare companies – is committed to improving the quality of human life by enabling people to do more, feel better, and live longer. For company information, visit GlaxoSmithKline at www.gsk.com.

Notes to editors

Arixtra ^®is a registered trade mark of the GlaxoSmithKline group of companies.

*Unstable angina/NSTEMI (Non-ST elevation myocardial infarction)

**STEMI (ST elevation myocardial infarction)

*** Enoxaparin (LOVENOX ^® ) is the registered trademark of Sanofi-Aventis.

Enquires

UK Media enquires: Phillip Thomson (020) 8047 5502

Joss Mathieson (020) 8047 5502

Gwenan White (020) 8047 5502

European Analyst/Investor enquires: Anita Kidgell (020) 8047 5542

David Mawdsley (020) 8047 5564

Sally Ferguson (020) 8047 5543

References

1. Committee for Medicinal Products for Human Use(CHMP). Summary of Opinion. Arixtra. June 2007

2. The Fifth Organization to Assess Strategies in Acute Ischemic Syndromes Investigators, Comparison of Fondaparinux and Enoxaparin in Acute Coronary Syndromes. N Engl J Med 2006 354: 1464-1476.

3. Effects of Fondaparinux on Mortality and Reinfarction in Patients with Acute ST-Segment Elevation Myocardial Infarction. JAMA 2006 295: 1519-1530.

4. Guidelines for the diagnosis and treatment of non-ST-segment elevation acute coronary syndromes: The Task Force for the Diagnosis and Treatment of Non-ST-Segment Elevation Acute Coronary Syndromes of the European Society of Cardiology Eur Heart J. 2007 Jun 14; [Epub ahead of print]

5. Acute Coronary Syndrome: Unstable Angina and Non-ST Segment Elevation Myocardial Infarction. British Medical Journal, June 7, 2003; 326:1259-1261.

6. Acute Coronary Syndrome: NSTEMI, Cardium Study #2, Decision Resources, July 2005.

7. Yusuf S, Flather M, Pogue J, et al. Variations between countries in invasive cardiac procedures and outcomes in patients with suspected unstable angina or myocardial infarction without initial ST elevation. OASIS (Organisation to Assess Strategies for Ischemic Syndromes) Registry Investigators. Lancet 1998 352: 507–14.