A recent evaluation by the independent German Institute for Quality and Efficiency in Health Care (IQWiG) provides additional support for the clinical use of the proprietary standardized ginkgo biloba extract EGb 761® in the treatment of dementia.1
IQWiG is the independent German organization responsible for providing national guidance on the promotion of good health and the prevention and treatment of disease (comparable to the British National Institute for Health and Clinical Excellence [NICE]). EGb 761 is a concentrated standardized extract of the leaves of ginkgo (Ginkgo biloba), produced by Dr. Wilmar Schwabe Pharmaceuticals of Karlsruhe, Germany, imported into the United States as Ginkgold® by Nature’s Way of Springville, Utah.
The objective of the IQWiG evaluation was to provide independent information on the benefits of the long-term use of the ginkgo extract in the treatment of Alzheimer’s dementia compared to placebo with respect to patient-relevant therapeutic measures. The IQWIG assessed 7 clinical studies conducted on approximately 1800 participants, all of which were treated with the EGb 761 special extract.
The IQWIG report includes the following findings:
• A dosage of 240 mg per day of EGb 761 has a proven and relevant benefit on Activities of Daily Life measurements.
• A dosage of 240 mg per day of EGb 761 has a proven and relevant benefit on the Clinical Global Impression scale.
• Published clinical studies demonstrate that cognitive abilities, neuropsychiatric symptoms, as well as the quality of life of care-giving relatives of patients with dementia are improved by daily use of EGb 761.
• Daily use of EGb 761 is safe and there are no data suggesting that ginkgo extract increases either minor or serious adverse events.
Officials at Schwabe emphasize that the IQWiG approval supports the role that the EGb 761 extract can continue to play in the treatment of dementia and early stages of Alzheimer’s disease, as opposed to their prevention. This point is particularly relevant in the wake of widespread media coverage of the recently-published 6-year Ginkgo Evaluation of Memory (GEM) clinical trial in the Journal of the American Medical Association in which a 240 mg daily dose of the ginkgo extract did not show benefits in preventing dementia.2
A Schwabe company spokesperson noted that, “In view of the recent findings of the GEM study these independent results [of IQWiG] strongly support our position that the symptomatic treatment of dementia and dementia prevention are two different things and need to be clearly distinguished from each other. The IQWiG evaluation once again confirms in an independent manner that EGb 761 is a valid treatment option for patients suffering from Alzheimer’s and that the known product benefits of EGb 761 remain undisputed” (e-mail, December 3, 2008).
In 2007 IQWiG also assessed the benefits of cholinesterase inhibitors (ChEIs), the conventional pharmaceutical drugs frequently employed in the treatment of dementia and Alzheimer’s disease.3 The IQWIG report stated that the ChEIs donepezil (Aracept®), galantamine (Razadyne®, Reminyl®), and rivastigmine (Exelon®) have a benefit in patients with mild-to-moderate Alzheimer's disease with regard to the therapy goal “improvement in or maintenance of cognitive function.”
The IQWiG report found that for these ChEIs, there are benefits related to the therapeutic goal of “improvement in or prevention of restriction in activities of daily living.” Furthermore, for galantamine there are data supporting its benefit regarding accompanying psychopathological symptoms. For donepezil no corresponding benefit could be inferred from the available data, and for rivastigmine, no data were available. Further, no data were available for galantamine and rivastigmine for the therapeutic goal of “improvement in or maintenance of health-related quality of life,” or they provided no indication of a benefit (donepezil). No interpretable data were available on the goal “prevention of placement in a nursing home” (institutionalization). All 3 drugs triggered therapy-related adverse events in a dose-dependent manner.
By comparison of the IQWiG clinical assessment of ChEIs with its assessment of the special ginkgo extract, the area referred to as “improvement in or maintenance of cognitive function” was the only effect for which IQWIG found a clinically proven benefit of ChEIs after analyzing the data from 27 clinical studies with 9883 participants. All of these trials contained deficiencies with respect to study and publication quality, with 16 containing minor and 11 having major deficiencies. Compared to the ginkgo extract clinical trials, only one study was deemed by IQWiG to be without deficiencies and the remaining trials showed only minor deficiencies.
Comparing the results of IQWiG’s evaluation of two standard treatment options for Alzheimer’s in Germany—EGb 761 vs. ChEI—true patient benefits appear to be more robust for EGb 761, which showed a clinically proven benefit in two of the major endpoints: "Activities of Daily Living" and "Clinical global impression" compared to a proven benefit of the ChEIs in only one, i.e., "Cognitive Function."
The bottom line, according to Schwabe scientists, relates to real-life benefits of the ginkgo extract compared to scores on cognitive assessment tests. “Taking a more patient-and caregiver-related viewpoint this is even more significant because an elderly Alzheimer patient and his [or her] family will find greater relief from the patient's being able to cope better with everyday tasks, such as finding his keys or the toilet, than from improved mental acuity.”
IQWiG is an independent scientific institute for health technology assessment that evaluates the quality and efficiency of health care. The institute investigates what therapeutic and diagnostic services are feasible and valuable, and communicates its findings to health care professions, patients and the general public. The Institute's tasks include the evaluation of pharmaceuticals, surgical procedures, diagnostic tests, clinical practice guidelines and aspects of disease management programs, following the principles of evidence-based medicine. It assesses the benefit and cost of drugs and publishes health information for patients and the general public. The Institute's primary goal is to contribute to improvements in health care in Germany. IQWiG receives commissions to perform such evaluations from the Federal Joint Committee and the Federal Ministry of Health.
—Mark Blumenthal
References
1. IQWiG. Ginkgohaltige Präparate bei Alzheimer Demenz. Abschlussbericht A05-19B. Cologne, Germany: Institut für Qualität und Wirtschaftlichkeit im Gesundheitswesen [Institute for Quality and Efficiency in Health Care (IQWiG)], 2008.
2. DeKosky ST, Williamson J, Fitzpatrick A, Kronmal RA, Ives DG, Saxton J, Lopez O, Burke G, Carlson M, Fried L, Kuller LH, Robbins J, Tracy RP, Woolard NF, Dunn L, Snitz BE, Nahin RL, Furberg CD for the GEM Study Investigators. Ginkgo biloba for primary prevention of dementia: Results of the Ginkgo Evaluation of Memory (GEM) Study. JAMA Nov 19, 2008;300(19):2253-2262.
3. IQWiG: Cholinesterase inhibitors in Alzheimer’s disease. Final report A05-19A. Cologne: Institute for Quality and Efficiency in Health Care (IQWiG); February 2007.
Available at: http://www.iqwig.de/download/A0519A_Final_Report_Cholinesterase_inhibitors_in_Alzheimers_disease.pdf.
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