SUPPLEMENT TO
Phase II Trials Appear to Validate
CGRP as a Promising Target in
the Treatment of Migraine
The four CGRP ligand and receptor monoclonal antibodies currently in clinical
trials appear to be effective for migraine prevention.
RIVIERA BEACH, FL—Monoclonal antibodies (MABs)
targeting calcitonin gene-related peptide (CGRP) will represent an important option in the treatment of migraine if
ongoing phase III trials meet or exceed the expectations
created by phase II data. When assessed by reduction in
headache days per month, the e;cacy of the four CGRP-targeted MABs in development has been relatively modest,
but a potentially clinically signi;cant minority of patients
in each of the phase II trials has become completely
headache-free.
;e development of therapies that block CGRP
has been a factor in rethinking the pathophysiology of
migraine, according to Alan M. Rapoport, MD, Clinical
Professor of Neurology at the David Ge;en School of Medicine at UCLA, Los Angeles, and Immediate Past President of the International Headache Society. Providing an
update on the promise of CGRP MABs at the 42nd Annual
Meeting of the Southern Clinical Neurological Society, Dr.
Rapoport reported that 31% of patients in one of a series
of phase II trials became headache-free, a rate he characterized as “never seen before” in a study of a migraine
therapy.
;e CGRP-targeted MABs represent the second major
attempt to target CGRP, a 37-amino-acid neuropeptide
chain ;rst isolated in the 1980s by Swedish investigator
Lars Edvinsson, MD, of Lund University. CGRP was among
several neuropeptides, such as substance P and neuro-
peptide Y, that have been considered attractive targets for
the treatment of migraine. In particular among these neu-
ropeptides, CGRP is a potent vasodilator and is strongly
implicated in trigeminal in;ammation, according to
Dr. Rapoport. Not least among evidence supporting CGRP
as a targetable mediator of migraine, CGRP has been
shown to be upregulated in patients with migraine.
CGRP receptors are widely distributed in the CNS,
according to Dr. Rapoport, although he acknowledged
that the exact site at which they trigger onset of migraine
remains an area of ongoing investigation. However, initial
clinical trials with CGRP receptor antagonists provided
a proof of principle. In a phase II study with the CGRP
receptor antagonist olcegepant, migraine response rates
relative to placebo (66% vs 25%) were substantial. ;is
agent, delivered IV, was also well tolerated.
;e IV delivery of olcegepant may at least partially
explain why commercial development was not pursued,
according to Dr. Rapoport, but a series of promising stud-
ies with chemically related oral agents soon followed, cul-
minating in a phase III trial of telcagepant. In that trial, the
300-mg dose of telcagepant and the 5-mg dose of zolmi-
triptan performed similarly, but telcagepant was better
2016 SCNS MEETING
Highlights from the
MARCH 2016
42ND ANNUAL MEETING OF THE SOUTHERN CLINICAL NEUROLOGICAL SOCIETY
Alan M. Rapoport, MD
