A New Class of Abortive Is in Development

In the early 90's, triptans such as Imitrex, Maxalt, Zomig, etc, revolutionized acute Migraine disease and cluster headache treatment. The triptans gave us a new class of abortives that worked to actually stop an attack and its associated symptoms in its tracks rather than just masking the pain. However, triptans aren't considered safe for all patients. Many patients with coronary disease have been unable to take advantage of them because action of constricting blood vessels is not limited to cerebral vessels but can also involve coronary vessels. That may change with a new class of medications.

Researchers in Europe and the United States are at work studying a new abortive medication for Migraine treatment. The drug, labeled BIBN4096 BS is a calcitonin gene-related peptide (CGRP) antagonist. They believe the neuropeptide CGRP is released from the trigeminal nerves and is involved in the pathophysiology of Migraine. Serum levels of CGRP are elevated in patients with cluster headaches and Migraine. Researchers began to study CGRP when clinical studies of triptans returned CGRP levels to normal when relieving Migraines or cluster headaches. Further, sensitive patients infused with CGRP experienced Migraines and cluster headaches.

CGRP is released from trigeminal ganglia nerves after nerve activation. It is a strong cerebral and dural vessel dilator, which regulates blood flow to the brain and pain-sensitive meninges. CGRP can cause release of inflammatory agents from meningeal mast cells and is involved in the transmission of pain producing stimuli from intracranial vessels to the central nervous system. Using a CGRP antagonist could be sufficient in treating Migraines and cluster headaches.

In a multicenter, double-blind trial, 126 patients with Migraine were randomized to receive placebo or 0.25, 0.5, 1.0, 2.5, 5.0, or 10.0 mg of BIBN 4096 BS as a 10-minute intravenous infusion. BIBN 4096 BS was effective for 60% of the total patients who received it and 66% of those who received the 2.5 mg dosage. Compared with placebo, 2.5 mg BIBN 4096 BS was significantly superior in terms of the pain-free rate at two hours; the sustained response rate over 24 hours; the rate of recurrence of headache; improvement in nausea, photophobia, phonophobia, and functional capacity; and the time to meaningful relief.

Adverse events occurred in 20% of the total patients receiving BIBN 4096 BS,  25% of the 2.5 mg group, and 12% of the group receiving placebo. The most common side effect reported was paresthesia. No serious side effects were reported.

The report of this study was published in the March 11 issue of the New England Journal of Medicine. In an accompanying editorial, Paul L. Durham, Ph.D., from Southwest Missouri State University in Springfield wrote:

"Given the apparent absence of vasoconstrictor activity with this agent, BIBN 4096 BS and possibly other CGRP-receptor antagonists may provide an alternative for the treatment of migraine that rivals triptans, although a formulation that may be administered as easily as the current triptans must first be developed ... It will be interesting to see whether CGRP-receptor antagonists also prove beneficial in treating other prevalent diseases, such as arthritis and temporomandibular-joint disorders, in which CGRP levels are elevated."

Although BIBN 4096 BS is still in early trials and other medications in the family have yet to be developed, the CGRP-receptor antagonists may well prove to be viable alternatives for those who cannot use triptans.

________________
References:

Olesen et al."Calcitonin Gene-Related Peptide Receptor Antagonist BIBN 4096 BS for the Acute Treatment of Migraine." New England Journal of Medicine, March 11, 2004; Vol. 350: pp. 1104-1110.
Jes Olesen, MD, Department of Neurology, Glostrup Hospital, University of Copenhagen, Denmark. Paul L. Durham, PhD, assistant professor of cell biology, Department of Biology, Southwest Missouri State University, Springfield, Missouri. William Young, MD, Jefferson Headache Center and assistant professor, Thomas Jefferson University, Philadelphia.

Laurie Barclay, MD. "Calcitonin Gene-Related Peptied Receptor Antagonist Effective in Acute Migraine. Medscape Medical News. April 12, 2004.