CoLucid Pharmaceuticals Announces Achievement of Secondary Endpoints in SAMURAI

  • 100 mg and 200 mg doses of lasmiditan were more efficacious than placebo on headache pain relief at the two-hour time point (p < 0.001)
  • 100 mg and 200 mg doses of lasmiditan were more efficacious than placebo as rescue medication on headache pain freedom at the two-hour time point (p < 0.001 and p < 0.012)
  • 100 mg and 200 mg doses of lasmiditan were more effective than placebo in reducing migraine related disability at two-hour time point (p < 0.001) and improving Patient Global Impression of Change (p < 0.001)
  • Second dose of lasmiditan was well tolerated and no significant difference in cardiovascular adverse events was observed in patients dosed with lasmiditan vs. placebo
  • Detailed results from SAMURAI presented at a symposium during the 5th European Headache and Migraine Trust International Congress (EHMTIC 2016) in Glasgow, Scotland on September 17, 2016

CAMBRIDGE, Mass., Sept. 17, 2016 (GLOBE NEWSWIRE) -- CoLucid Pharmaceuticals, Inc., a biopharmaceutical company that is developing lasmiditan oral tablets for the acute treatment of migraine in adults, with or without aura, announced today that its Phase 3 pivotal trial evaluating lasmiditan, the SAMURAI study, had achieved secondary endpoints with statistical significance (p < 0.001 – p < 0.012). SAMURAI was a randomized, double-blind, placebo-controlled parallel group study designed to evaluate the efficacy and safety of lasmiditan (100 mg and 200 mg) in comparison to placebo. Lasmiditan doses of 100 mg and 200 mg were efficacious on headache pain freedom and the most bothersome symptom (MBS) freedom at the two-hour time point (p < 0.001), the primary and key secondary endpoints of the study. SAMURAI is the first of two Phase 3 pivotal trials of lasmiditan, each being conducted under a Special Protocol Assessment agreement (“SPA”) with the U.S. Food and Drug Administration (“FDA”).

Secondary Endpoints

Efficacy

Secondary efficacy endpoints of lasmiditan (100 mg and 200 mg) in SAMURAI included:

  • the efficacy of lasmiditan in comparison to placebo based on migraine headache pain relief two hours after dosing in the intent to treat (ITT) population
  • the efficacy of lasmiditan in comparison to placebo based on freedom from migraine headache pain two hours after dosing when used as a second dose for either rescue or recurrence in the ITT population
  • the efficacy of lasmiditan in comparison to placebo based on the proportion of patients absent each associated symptom of migraine (nausea, phonophobia or photophobia) two hours after dosing in the ITT population
  • the efficacy of lasmiditan in comparison to placebo based on Patient Global Impression of Change (PGIC) two hours after dosing in the ITT population
  • the efficacy of lasmiditan in comparison to placebo based on disability related to migraine two hours after dosing in the ITT population

Data from the 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. 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. At the two-hour endpoint, patients indicated their Patient Global Impression of Change (very much better, much better, a little better, no change, a little worse, much worse, very much worse). At the two-hour endpoint, patients also indicated their disability related to migraine on a 4-point scale: 0, not at all; 1, mild interference; 2, marked interference; 3, completely, needs bed rest.

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 in relieving migraine headache pain at two hours (p < 0.001) as compared to placebo.

HEADACHE PAIN RELIEF (ITT)Lasmiditan
100mg
Lasmiditan
200mg
Placebo
% of patients migraine headache pain relief at two hours 59.4% 59.5% 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 were randomized at 2:1 lasmiditan to placebo for a second dose, unless the initial dose was placebo. Patients were allowed to take a second dose of study drug after the two-hour time point, but before the 24-hour time point, for rescue or recurrence. Rescue was defined as a second dose taken for a migraine for which headache pain freedom was not achieved at the two-hour time point after initial dosing. Recurrence was defined as a second dose taken for a migraine for which headache pain freedom was achieved at the two-hour time point but reoccurred within 24 hours after initial dosing. The utilization rate of a second dose was expressed as the proportion of patients who took any second dose of study drug in a treatment group to the safety population of the same treatment group.

Patients dosed with lasmiditan were less likely to use a second dose of study drug. Lasmiditan was effective on migraine headache pain freedom at the two-hour time point assessment following a second dose as a rescue medication as compared to placebo. The number of patients who took a second dose of study drug for recurrence was small (53 out of 1,671) with no significant difference between five treatment groups.

SECOND DOSE UTILIZATIONLasmiditan 100mg
(n=630)
Lasmiditan 200mg
(n=609)
Placebo
(n=617)
Patients taking a second dose of study drug 289 236 401
Utilization rate of a second dose of study drug 46% 39% 65%


SECOND DOSE HEADACHE PAIN FREEDOM (ITT)100mg/
100mg
(n=139)
100mg/
Placebo
(n=62)
200mg/
200mg
(n=109)
200mg/
Placebo
(n=52)
Placebo/
Placebo
(n=319)
% of Patients Pain Free at two hours after Rescue Dose 29.0% 12.9% 26.6% 23.1% 16.9%
Odds ratio (95% confidence interval)2.2 (1.4 - 3.6) 2.0 (1.2 – 3.3)
p value< 0.001 < 0.012

The MBS endpoint was patient-centric and measured treatment effect of study drug on associated symptoms of nausea, phonophobia and photophobia. Freedom from MBS at the two-hour time point assessment was a key secondary endpoint of SAMURAI and conforms to the FDA’s Draft Guidance for Industry, Migraine: Developing Drugs for Acute Treatment, issued in October 2014. Patients treated with lasmiditan 100 mg or 200 mg were more likely to be MBS free at the two-hour time point assessment than patients treated with placebo (p < 0.001).

The distribution of baseline associated symptoms present in each dose group was relatively even.

BASELINE ASSOCIATED SYMPTOMS, n (%)Lasmiditan
100mg

(n=503)
Lasmiditan
200mg

(n=518)
Placebo
(n=554)
Nausea210 (41.7%)232 (44.8%)221 (42.2%)
Phonophobia303 (60.2%)322 (62.2%)327 (62.4%)
Photophobia386 (76.7%)391 (75.5%)416 (79.4%)
None34 (6.8%)37 (7.1%)36 (6.9%)

However, patients were more likely to select photophobia as MBS if it were present at baseline than nausea or phonophobia. This selection preference was expressed as a proportion of the number of patients who selected that baseline associated symptom as most bothersome versus the number of patients that had the baseline symptom.

MBS SELECTED (mITT)Selection Preference of MBS
Nausea 52%
Phonophobia 33%
Photophobia 65%

The proportion of patients absent each associated symptom of migraine (nausea, phonophobia or photophobia) two hours after dosing was also measured as a secondary endpoint.

ASSOCIATED SYMPTOMS (ITT)Lasmiditan 100mg
(n=562)
Lasmiditan 200mg
(n=555)
Placebo
(n=554)
% of patients nausea free at two hours 64.6% 64.1% 62.1%
% of patients phonophobia free at two hours 60.7% 58.7% 52.5%
% of patients photophobia free at two hours 53.9% 51.5% 38.1%

Patients dosed with lasmiditan had a positive Patient Global Impression of Change (p < 0.001). The proportion of patients with a Patient Global Impression of Change of much or very much better at two hours was 37.2% for lasmiditan 100 mg treated patients, 37.8% for lasmiditan 200 mg treated patients, and 21.8% for placebo treated patients.

PATIENT GLOBAL IMPRESSION OF CHANGE [PGIC] (ITT)Lasmiditan
100mg

(n=562)
Lasmiditan
200mg

(n=555)
Placebo
(n=554)
PGIC 2-hours post-dose, n (%)
Very Much Better54 (9.6%)57 (10.3%)34 (6.1%)
Much Better155 (27.6%)153 (27.6%)87 (15.7%)
A Little Better153 (27.2%)143 (25.8%)159 (28.7%)
No Change83 (14.8%)60 (10.8%)146 (26.4%)
A Little Worse16 (2.8%)31 (5.6%)28 (5.1%)
Much Worse8 (1.4%)13 (2.3%)14 (2.5%)
Very Much Worse8 (1.4%)5 (0.9%)3 (0.5%)
Missing85 (15.1%)93 (16.8%)83 (15.0%)
p value< 0.001< 0.001

Patients dosed with lasmiditan had a significant reduction in disability related to migraine at the two-hour time point assessment.

MIGRAINE DISABILITY AT TWO HOURS POST DOSE (ITT)Lasmiditan 100mg
(n=562)
Lasmiditan 200mg
(n=555)
Placebo
(n=554)
Disability 2-hours post-dose, n (%)
Not at All (0)181 (32.2%)180 (32.4%)119 (21.5%)
Mild Interference (1)137 (24.4%)115 (20.7%)156 (28.2%)
Marked Interference (2)95 (16.9%)92 (16.6%)122 (22.0%)
Completely, Needs Bed Rest (3)64 (11.4%)75 (13.5%)74 (13.4%)
p value< 0.001< 0.001

Adverse Events

Lasmiditan was well tolerated as a second dose, with the majority of treatment emergent adverse events (TEAE) being nervous system related, and 99.8% of second dose TEAE in lasmiditan treated patients being described as mild or moderate in nature. Importantly, there was not a significant increase in cardiovascular adverse events in patients who took a second dose of lasmiditan versus placebo. The following table sets forth the percentage of patients who experienced the specified treatment emergent adverse event within the safety population following a second dose of study drug.

TEAE FOLLOWING SECOND DOSE100mg/
100mg
(n=203)
100mg/
Placebo
(n=86)
200mg/
200mg
(n=159)
200mg/
Placebo
(n=79)
Placebo/
Placebo
(n=401)
Dizziness5 (2.5%)7 (8.1%)12 (7.5%)9 (11.4%)6 (1.5%)
Somnolence7 (3.4%)2 (2.3%)1 (0.6%)1 (1.3%)3 (0.7%)
Paresthesia3 (1.5%)2 (2.3%)01 (1.3%)6 (1.5%)
Fatigue5 (2.5%)1 (1.2%)2 (1.3%)1 (1.3%)2 (0.5%)
Nausea3 (1.5%)1 (1.2%)1 (0.6%)2 (2.5%)3 (0.7%)
Vomiting2 (1.0)01 (0.6%)1 (1.3%)3 (0.7%)
Muscular Weakness3 (1.5%)0000
Asthenia001 (0.6%)2 (2.5%)1 (0.2%)
Tachycardia01 (1.2%)000
Palpitations1 (0.5%)0000

Analysis

Analysis was conducted using a one-sided test from a logistic regression model with treatment group and background use of medication to reduce the frequency of migraines as covariates.

Symposium

Detailed results from SAMURAI were presented at a symposium during the 5th European Headache and Migraine Trust International Congress (EHMTIC 2016) that took place in Glasgow, Scotland on September 17, 2016. A copy of the presentation that was utilized at the symposium is available on CoLucid’s website at: http://www.colucid.com/wp-content/uploads/2016/09/SAMURAI-Results-for-EHMTIC-2016-FINAL.pdf

“We have shown in SAMURAI across multiple secondary endpoints that lasmiditan was effective in treating migraine headache pain and reducing patients’ disability related to their migraine,” said Bernice Kuca, Head – Clinical and Regulatory Operations at CoLucid. “We are also very pleased that, based on the study results, lasmiditan appears to be effective as a rescue medication and the tolerability profile of lasmiditan after a second dose looks good, with patients’ impressions of lasmiditan being favorable as measured by the Patient Global Impression of Change. We look forward to further analyses of SAMURAI data.”

About Lasmiditan
Lasmiditan has been designed for the acute treatment of migraine headaches in adults without the vasoconstrictor activity associated with previous generations of migraine therapies. It selectively targets 5-HT1F 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 a second pivotal Phase 3 clinical trial of lasmiditan oral tablets, SPARTAN. The objective of SPARTAN is to evaluate the safety and efficacy of lasmiditan (50 mg, 100 mg and 200 mg) in comparison to placebo two hours after dosing on freedom from migraine headache pain, which is the primary endpoint, and on freedom from the most bothersome associated symptom of migraine (nausea, phonophobia or photophobia), which is the key secondary endpoint. SPARTAN is a randomized, double-blind, placebo-controlled parallel group study. The study is expected to treat a single migraine in up to 2,226 migraine patients with lasmiditan at approximately 140 sites in the United States, United Kingdom and Germany. CoLucid expects that migraine patients enrolled in SPARTAN will include those who also have one or more cardiovascular risk factors, stable cardiovascular disease or known coronary artery disease (“CAD”). CoLucid has obtained an SPA agreement from the FDA for SPARTAN. Top-line results from SPARTAN are expected in the second half of 2017.

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 have completed CoLucid’s first Phase 3 pivotal trial, SAMURAI, as well as CoLucid’s second Phase 3 pivotal trial, SPARTAN, are eligible to enroll in GLADIATOR. GLADIATOR is expected to enroll up to a total of 2,580 patients, 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.

About CoLucid Pharmaceuticals, Inc.
CoLucid (Nasdaq:CLCD) was founded in 2005 and is developing lasmiditan oral tablets 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, anticipated marked demand, anticipated physician prescribing patterns, clinical trial enrollment goals and the timing of future clinical trials. Actual enrollment results, market demand, use of cash and other 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, regulatory approval may not be obtained, physicians may not prescribe lasmiditan, and projected cash needs and expected financial results may be different. 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.


CONTACT Thomas Mathers Chief Executive Officer CoLucid Pharmaceuticals, Inc. (857) 285-6494 Hans Vitzthum Managing Director LifeSci Advisors, LLC. (212) 915-2568

Source:CoLucid Pharmaceuticals, Inc