Merck halts clinical development program for CGRP antagonist Telcagepant
With the CGRP antagonists MK-0974 and MK-3207, a new therapeutic mechanism in migraine treatment has been developed for clinical application. These are two CGRP antagonists currently undergoing clinical research programs for the treatment of migraine. CGRP antagonists were considered the key innovation in migraine treatment for the coming years.
Development of the drug MK-3207 was halted in 2009. Further Phase IIb and III trials were not initiated. Efficacy was demonstrated in the existing studies. However, the investigations revealed that delayed increases in liver enzyme levels could occur in isolated cases. Based on this, it was decided not to further develop the CGRP antagonist MK-3207.
The development of the CGRP antagonist MK-0974 (telcagepant) has continued. The active ingredient telcagepant has opened up the option of a clinically applicable CGRP receptor antagonist for the acute treatment of migraine. It possesses a novel mechanism of action, as it can both terminate migraine attacks and does not cause vasoconstriction or act via the serotonin mechanism. CGRP and its receptors are found in many areas of the brain. According to current research, CGRP plays a crucial role in the transmission of migraine pain. During a migraine attack, CGRP binds to and activates CGRP receptors, thereby transmitting pain signals. MK-0974 (telcagepant) is able to block CGRP at these receptors and can thus stop the transmission of pain signals and migraine attacks.
Studies have demonstrated its clinical efficacy in stopping migraine attacks. While similar in efficacy to triptans, telcagepant does not have the vasoconstrictive side effects of triptans.
Due to elevated liver enzyme levels in individual patients, the approval of telcagepant was delayed. These were additional studies for the prevention of migraine attacks, in which the drug was administered twice daily for three months for long-term migraine prevention. Elevated liver enzyme levels were 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 evaluation of further safety studies, including a recent six-month Phase III study, led to the announcement on July 29, 2011, that the clinical development of Telcagepant will not be continued.
Merck said it is discontinuing the clinical development program for telcagepant, the company's investigational calcitonin gene-related peptide receptor antagonist for the treatment of acute migraine. The decision is based on an assessment of data across the clinical program, including findings from a recently completed six-month Phase III study.
There are many – not just older – migraine patients who need to take vasoconstrictor medications.
Telcagepant would have been the attack therapy of choice! By the way, liver values have to be checked even during prophylaxis with Petasites!
Best regards,
Margarete Schmidt-Breuer,
suffering from migraines for 50 years
There's more to it than that - I see a simple increase in transamine levels every day when taking NSAIDs - that's why no study was stopped.
It would be interesting to look at the study documents at this point in time, then we would know the whole truth... Are there other studies that focus on neurogenic inflammation of the vessels leading to the brain, or was that the only glimmer of hope?
Dr. Babel
Thanks for the information. It's a shame, because now 10 years of research have been in vain and we are one hope poorer.
Many greetings,
Bettina Frank