CoLucid Pharmaceuticals Announces Confirmatory Support for Non-vasoconstrictive Mechanism of Action for Lasmiditan

February 23, 2016

CAMBRIDGE, Mass., Feb. 23, 2016 (GLOBE NEWSWIRE) -- CoLucid Pharmaceuticals, Inc. (NASDAQ:CLCD), a Phase 3 clinical-stage biopharmaceutical company that is developing its lead product candidate, lasmiditan, for the acute treatment of migraine headaches, announced today the completion of a preclinical /in vivo /study examining the effect of lasmiditan on coronary and carotid artery diameters. This study confirms the lack of effect of lasmiditan on coronary artery and carotid artery vasoconstriction; the data are expected to be used in support of potential future regulatory filings.

In this study conducted by CorDynamics in Chicago, IL, lasmiditan was directly compared to sumatriptan, the most widely prescribed acute treatment for migraine. Lasmiditan, sumatriptan and vehicle control were administered by intravenous infusion in escalating cumulative doses ranging from 0.03 to 11.13 mg/kg. Significant decreases in both carotid and coronary diameters were observed in sumatriptan-treated animals even at 0.03 mg/kg, which is calculated to be the equivalent to the lowest approved oral clinical dose of 25 mg. Conversely, lasmiditan did not induce any significant decrease in arterial diameters at any dose tested. Lasmiditan plasma concentrations reached above 3,500 ng/mL following a cumulative dose of 11.13 mg/kg, which is significantly above the highest exposure achieved in clinical settings.

“Lasmiditan is highly selective for the serotonin receptor 5-HT_1F ,”
stated Dr. Joseph Kovalchin, Director of Research. “Triptans are thought to treat migraines by inducing vasoconstriction through other serotonin receptors (5-HT_1B/1D ) on cranial blood vessels; however, triptans also induce unwanted vasoconstriction of the coronary and carotid arteries.
The lack of vasoconstrictive effect of lasmiditan in this model reinforces the fact that targeting 5-HT_1F does not trigger the same undesirable effects.”

Data from this study, which has been conducted in accordance with Good Laboratory Practice (GLP), as well as from other experimental investigations, will be submitted for publication in a peer-reviewed journal, and presented at an upcoming international conference.

“These new data confirm and expand on our hypothesis that lasmiditan may be a more appropriate choice to treat migraine patients who have cardiovascular risk factors and coronary artery disease,” stated Thomas P. Mathers, Chief Executive Officer. “The Food and Drug Administration has asked us to confirm lasmiditan’s lack of vasoconstrictive effect on coronary arteries to support potential labeling discussions in migraine patients with cardiovascular comorbidities. We are very pleased with the data from this preclinical GLP study.”

*/About Lasmiditan/*
Lasmiditan has been designed to deliver efficacy for the acute treatment of migraine headaches in adults without the vasoconstrictor activity associated with previous generations of migraine therapies.  It selectively targets 5-HT_1F receptors expressed in the trigeminal pathway.  Lasmiditan has been given the generic stem name “ditan,” which distinguishes it from other drug classes, including triptans, the current standard of care for migraine.

CoLucid is currently enrolling patients in SAMURAI, its first of two pivotal phase 3 clinical trials. The objective of SAMURAI is to evaluate the safety and efficacy of lasmiditan (100 mg and 200 mg) in comparison to placebo two hours after dosing on freedom from migraine headache pain, which is our primary endpoint, and on freedom from the most bothersome associated symptom of migraine (nausea, phonophobia or photophobia), which is our secondary endpoint.  SAMURAI is a randomized, double-blind, placebo-controlled parallel group study.  The study is expected to treat a single migraine in up to 1,483 migraine patients with lasmiditan at approximately 70 U.S. sites.  CoLucid expects patients will include those with migraine who also have cardiovascular risk factors or cardiovascular disease. SAMURAI is being conducted under a Special Protocol agreement with the U.S. Food and Drug Administration.
Lasmiditan is designed to address major unmet medical needs in patients who are poorly served by currently available therapies, including patients with cardiovascular risk factors or cardiovascular disease who may not be able to take triptans.

CoLucid is also currently enrolling patients in GLADIATOR, a Phase 3 long-term, open-label trial of lasmiditan. GLADIATOR’s objective is to evaluate the safety and efficacy of lasmiditan, as well as resource utilization, functional outcomes and disability. Migraine patients who complete CoLucid’s ongoing first Phase 3 pivotal trial, SAMURAI, as well as the Company’s second Phase 3 pivotal trial, scheduled to commence in the first half of 2016, will be eligible to enroll in GLADIATOR.
GLADIATOR is expected to enroll up to a total of 2,580 subjects, who will be randomized to receive 100 mg or 200 mg of lasmiditan, and treated for up to eight migraine attacks per month for one year. Based on the results of GLADIATOR, CoLucid intends to build an appropriate safety database to support a New Drug Application (“NDA”) for lasmiditan. At the time of the NDA submission, it is anticipated that there will be more than 15,000 patient exposures to lasmiditan in the entire clinical program.

*/About Migraine/*
Migraine is the leading cause of disability among neurological disorders in the United States according to the American Migraine Foundation.  An estimated 36 million Americans suffer from migraine.  Migraine can be extremely disabling and costly, accounting for more than an estimated
$20 billion in direct (e.g., doctor visits, medications) and indirect (e.g., missed work, lost productivity) expenses each year in the United States. Most (57%) of the patients diagnosed with migraine and receiving treatment are 40 years and older. Migraine patients have a substantially increased rate of experiencing a CAD event compared to the general population (9.9% compared to 6.4%) and 76%, or 2.8 million, of adult patients diagnosed with migraine have cardiovascular conditions or risk factors that contraindicate or warn against triptan use.

*/About CoLucid Pharmaceuticals, Inc./*
CoLucid is developing oral lasmiditan for the acute treatment of migraine headaches in adults and intravenous lasmiditan for the acute treatment of headache pain associated with migraine in adults in emergency room and other urgent care settings.

*Forward-Looking Statements*

/Certain of the statements made in this press release are forward looking, such as those, among others, relating to CoLucid’s expectations for lasmiditan’s efficacy, potential as a treatment option for migraine, and potential to be used to treat migraine patients with cardiovascular
risk factors and coronary artery disease.   Developments may occur that
differ materially from those projected or implied in these forward-looking statements. Factors that may cause such a difference include risks that enrollment goals will not be met, trials may not be commenced or successful or may take longer to complete than anticipated, and projected cash needs and expected financial results may be different, as well as physicians may not prescribe lasmiditan. More information about the risks and uncertainties faced by CoLucid are contained in its periodic reports filed with the Securities and Exchange Commission. CoLucid disclaims any intention or obligation to update or revise any forward-looking statements, whether as a result of new information, future events or otherwise./

Thomas Mathers
Chief Executive Officer
CoLucid Pharmaceuticals, Inc.
(857) 285-6495

Hans Vitzthum
Managing Director
LifeSci Advisors, LLC.
(212) 915-2568