CoLucid Pharmaceuticals (CLCD) Offers Analyses of Lasmiditan's Onset of Action Data from SAMURAI Study

October 5, 2016 10:56 AM EDT
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CoLucid Pharmaceuticals, Inc. (Nasdaq: CLCD), a biopharmaceutical company that is developing lasmiditan oral tablets for the acute treatment of migraine in adults, with or without aura, provided additional data regarding onset of action demonstrated as soon as 30 minutes after dosing for 100 mg and 200 mg of lasmiditan from its Phase 3 pivotal trial evaluating lasmiditan, the SAMURAI study. In addition, CoLucid had presented non-clinical data at the 5th European Headache and Migraine Trust International Congress (EHMTIC) in Glasgow, Scotland, U.K., supporting the mechanism of action of lasmiditan through central nervous system (CNS) penetration, distribution into areas of the brain relevant to migraine pathophysiology, expression of the 5-HTIF receptor mRNA in relevant regions of the brain, inhibition of trigeminal nociceptive responses, and lack of any vasoconstrictive activity in non-clinical models.

Data from the SAMURAI study were collected using electronic diaries during the treated attack. Beginning pre-dose, patients indicated their degree of headache pain on a 4-point scale: 0, no pain; 1, mild pain; 2, moderate pain; or 3, severe pain. Migraine headache relief was defined as moderate or severe headache pain at baseline reduced to mild or no headache pain at the time point assessment. Lasmiditan was effective at both the 100 mg dose and the 200 mg dose in relieving migraine headache pain as soon as 30 minutes (p 0.004) as compared to placebo. The following table sets forth the number and percentage of patients in the intent to treat (ITT) population who experienced headache pain relief during the two hours following dosing and a comparison of each to dose to placebo.

HEADACHE PAIN RELIEF (ITT)Lasmiditan 100mg(N=562)Lasmiditan 200mg(N=555)Placebo(N=554)
Number (%) of patients migraine headache pain relief at 30 minutes106 (18.9%)106 (19.1%)70 (12.6%)
Odds Ratio (95% confidence interval)1.6 (1.2, 2.3)1.7 (1.2, 2.4)
p-valuep = 0.004p = 0.002
Number (%) of patients migraine headache pain relief at 1 hour232 (41.3%)241 (43.4%)164 (29.6%)
Odds Ratio (95% confidence interval)1.8 (1.3, 2.3)2.1 (1.6, 2.7)
p-valuep < 0.001p < 0.001
Number (%) of patients migraine headache pain relief at 1 ½ hours303 (53.9%)296 (53.3%)216 (39.0%)
Odds Ratio (95% confidence interval)2.0 (1.6, 2.6)2.1 (1.6, 2.8)
p-valuep < 0.001p < 0.001
Number (%) of patients migraine headache pain relief at 2 hours334 (59.4%)330 (59.5%)234 (42.2%)
Odds Ratio (95% confidence interval)2.4 (1.8, 3.1)2.5 (1.9, 3.3)
p-valuep < 0.001p < 0.001

Patients also indicated the presence or absence of nausea, phonophobia or photophobia, and at the pre-dose time point identified the associated symptom present that was “most bothersome.” At each time point assessment, patients were asked to indicate the degree of headache pain and the presence or absence of each associated symptom. The MBS endpoint was patient-centric and measured treatment effect of study drug on associated symptoms. Lasmiditan treated patients were more likely to achieve MBS freedom as soon as 30 minutes after dosing (p 0.015) as compared to patients treated with placebo. The following table sets forth the number of patients in the modified ITT (mITT) population who recorded a MBS at the time of dosing and the number and percentage of those patients who experienced MBS freedom during the two hours following dosing, as well as a comparison of each dose to placebo.

MBS FREE (mITT)Lasmiditan 100mgN=503Lasmiditan 200mgN=518PlaceboN=524
MBS recorded at time of dosing469481488
Number (%) of patients MBS free at 30 minutes59 (12.6%)61 (12.7%)38 (7.8%)
Odds Ratio (95% confidence interval)1.7 (1.1, 2.6)1.7 (1.1, 2.6)
p-valuep = 0.015p = 0.013
Number (%) of patients MBS free at 1 hour129 (27.5%)130 (27.0%)84 (17.2%)
Odds Ratio (95% confidence interval)1.8 (1.3, 2.5)1.8 (1.3, 2.4)
p-valuep < 0.001p < 0.001
Number (%) of patients MBS free at 1 ½ hours162 (34.5%)161 (33.5%)117 (24.0%)
Odds Ratio (95% confidence interval)1.7 (1.3, 2.2)1.6 (1.2, 2.1)
p-valuep < 0.001p = 0.001
Number (%) of patients MBS free at 2 hours192 (40.9%)196 (40.7%)144 (29.5%)
Odds Ratio (95% confidence interval)1.7 (1.3, 2.2)1.6 (1.3, 2.1)
p-valuep < 0.001p < 0.001

The onset of action of lasmiditan as soon as 30 minutes after dosing in SAMURAI is consistent with findings presented at EHMTIC on September 15-18, 2016. In a poster presentation by Joseph Kovalchin, Ph.D. (CoLucid), in vivo non-clinical models demonstrated that lasmiditan was able to cross the blood brain barrier as early as 30 minutes after oral or IV dosing. Lasmiditan was also shown to distribute to areas of the brain relevant to migraine.

In a poster presented by Marta Vila-Pueyo from Dr. Philip Holland’s laboratory at King’s College London, U.K., IV lasmiditan significantly inhibited trigeminal nociceptive responses in rats as early as 30 minutes after dosing, which is indicative of acute anti-migraine therapeutic efficacy. Moreover, 5-HT1F receptor mRNA was found widely expressed in cortical, diencephalic and brainstem regions of the human brain known to be of importance to migraine pathophysiology. Together, the data suggests that, unlike triptan therapies, lasmiditan likely acts directly in brain regions involved in the pathophysiology of migraine that express 5-HT1F receptor mRNA.

  • A copy of the Kovalchin poster is available on CoLucid’s website at: http://www.colucid.com/wp-content/uploads/2016/10/CoLucid-Kovalchin-Poster-90x120-13-Sep-16.pdf
  • A copy of the Vila-Pueyo poster is available at: http://www.colucid.com/wp-content/uploads/2016/10/Vila-Pueyo-poster.pdf

Lasmiditan was also shown to be devoid of vasoconstrictive activity in the coronary and carotid arteries in non-clinical models. In a poster presented by Elíosa Rubio-Beltran from Dr. Antoinette Maassen van den Brink’s laboratory at Erasmus University Medical Center, Rotterdam, The Netherlands, lasmiditan was evaluated for vasoconstrictive activity using in vitro assays with either human internal mammary or human coronary arteries. Under normal and/or pre-contractile conditions, the latter achieved by using threshold concentrations of the thromboxane A2 analogue U46619, lasmiditan had no vasoconstrictive activity even at supratherapeutic concentrations. Sumatriptan, the most widely prescribed triptan in 2015, according to IMS Analytics, was shown to induce vasoconstriction of human coronary arteries, already at clinically relevant concentrations. The distal coronary arteries were shown to have had greater vasoconstriction in response to sumatriptan than the proximal coronary arteries. In an in vivo model conducted by CorDynamics (Chicago, IL), lasmiditan showed no vasoconstrictive activity in the coronary and carotid arteries, even at supratherapeutic doses. Sumatriptan, used as positive control, induced significant vasoconstriction of both the coronary and carotid arteries, at doses calculated to be clinically relevant. A copy of the Rubio-Beltran poster is available on CoLucid’s website at: http://www.colucid.com/wp-content/uploads/2016/10/Rubio-Beltran-poster.pdf

“One of the greatest unmet needs in the acute treatment of migraine is speed of relief for patients suffering from an attack,” said Thomas P. Mathers, President and CEO of CoLucid. “The SAMURAI trial provides important data regarding onset of action of lasmiditan in treating migraine headache pain as well as the most bothersome associated symptom to the patient. We know that rapid relief is clinically meaningful to the patients during a migraine attack - patients want to feel better, and fast. We will continue to analyze the data and study lasmiditan, with the hope that it can provide relief utilizing a novel mechanism of action that does not have the vasoconstrictive effects of other acute treatments such as triptans.”



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