Dr. Silberstein, Prof. Goadsby, Dr. Dodick
During the International Headache Congress on September 10, 2009, in Philadelphia, USA, numerous new data on the development of the CGRP antagonists MK-0974 and MK-3207 were presented. These are two CGRP antagonists currently in clinical research programs for the treatment of migraine. CGRP antagonists are considered the key innovation in migraine treatment for the coming years. Surprisingly, however, the development of the drug MK-3207 was halted. Further Phase IIb and III trials will not be initiated. While efficacy has been demonstrated in previous studies, these investigations revealed that delayed increases in liver enzyme levels can occur in isolated cases. Based on this, the decision to discontinue further development of the CGRP antagonist MK-3207 was announced on September 10, 2009.
The development was lamented by scientists at the International Headache Congress, as it means that one less option is available for the care of headache patients, in which great hopes had been placed.
Nevertheless, the development of the CGRP antagonist MK-0974 (telcagepant) will continue. The active ingredient MK-0974 is also a novel CGRP receptor antagonist. It possesses a novel mechanism of action, as it can, on the one hand, abort migraine attacks, and on the other hand, does not cause vasoconstriction and does not act via the serotonin mechanism. CGRP and its receptors are found in many areas of the brain. According to current research, CGRP is crucial for the transmission of migraine pain. During a migraine attack, CGRP binds to and activates CGRP receptors. This transmits pain signals. MK-0974 (telcagepant) is able to block CGRP at the receptors and can thus stop the transmission of pain signals and migraine attacks.
CGRP antagonists in clinical development
In April 2009, the manufacturer announced that it would not submit a marketing authorization application for telcagepant due to elevated liver enzyme levels in some patients. However, these were studies on migraine prevention, in which the drug was administered twice daily for three months as a long-term preventative measure. Elevated liver enzyme levels were also detected in three patients during these studies. However, the dosage and frequency of administration in the migraine prevention studies differed from the studies in which the drug was used intermittently for the acute treatment of individual migraine attacks.
The current data situation will now be discussed with the regulatory authorities in order to decide on the next steps.
Further information
http://www.merck.com/newsroom/press_releases/research_and_development/2009_0910.html
Philadelphia Convention Center
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