CoLucid Pharmaceuticals Announces Achievement of Both Primary and Key Secondary Endpoints in the SAMURAI Phase 3 Pivotal Trial of Lasmiditan in Migraine
Cambridge, MA, September 6, 2016 -- 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 study evaluating lasmiditan, the SAMURAI study, achieved both the primary and key secondary efficacy endpoints with statistical significance (p < 0.001). Lasmiditan was also well tolerated. 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. 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”).
The primary endpoint of SAMURAI was the efficacy of lasmiditan (100 mg and 200 mg) in comparison to placebo based on freedom from migraine headache pain two hours after dosing. The key secondary endpoint was the efficacy of lasmiditan based on freedom from the most bothersome associated symptom (MBS) of migraine (nausea, phonophobia or photophobia) two hours after dosing. 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. The MBS endpoint was patient-centric and measured treatment effect of study drug on associated symptoms. Both the primary and key secondary endpoints of SAMURAI conform to the FDA’s Draft Guidance for Industry, Migraine: Developing Drugs for Acute Treatment, issued in October 2014.
Lasmiditan was well tolerated, with the majority of treatment emergent adverse events (TEAE) being nervous system related, and 91% of 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 dosed with lasmiditan versus placebo. There were no serious adverse events in SAMURAI that were considered to be related to treatment. The following table sets forth the percentage of patients who experienced the specified adverse event within the safety population for each dose.
2,231 patients were randomized at approximately 80 U.S. sites to participate in SAMURAI to treat a single migraine. Patients randomized had a mean age of 41.6 years, 83% were females, and 74% were Caucasian, with a mean migraine history of over 19 years. Patients randomized experienced an average of over five migraines per month and suffered severe disability from migraine, with an average MIDAS (Migraine Disability Assessment) score of 31. Over 25% of patients randomized used prophylactic medication to reduce the frequency of migraine. 82% of patients randomized had multiple cardiovascular risk factors (CVRF) or cardiovascular conditions. The most prevalent CVRF were obesity, family history of coronary artery disease (CAD), smoking, hypertension, post-menopausal women, men over 40 years of age, hyperlipidemia and type 2 diabetes. The most prevalent cardiovascular conditions were arrhythmias, mitral valve disease, angina, atrial fibrillation, congestive heart failure, prior myocardial infarction, Raynaud’s disease, deep vein thrombosis, ischemic stroke, and cerebral infarction.
In accordance with the SPA agreement for SAMURAI, the protocol pre-specified the analysis population as the modified intent to treat population (mITT). The mITT was defined in the protocol as all randomized patients who used at least one dose of study drug to treat a qualifying migraine attack and had any post-dose assessments. Patients were evaluated by the study medication to which they were randomized and a qualifying migraine attack was defined as a migraine treated with study drug within four hours of onset. Similar to other migraine clinical trials, approximately 30% of patients randomized in SAMURAI were not included in the mITT due to either a failure to dose a qualifying migraine during the trial, failure to use the electronic diaries for any time point assessment, or post-randomization ineligibility (clinical lab values). In the trial, 1,239 patients took at least one dose of lasmiditan versus 617 who took at least one dose of placebo. The mITT consisted of 1,021 patients who took lasmiditan and 524 who took placebo. 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.
Detailed results from SAMURAI will be presented at a symposium during the 5th European Headache and Migraine Trust International Congress (EHMTIC 2016) taking place in Glasgow, Scotland on September 17, 2016.
Richard B. Lipton, MD, Edwin S. Lowe Professor and Vice Chair of Neurology, Professor of Epidemiology and Population Health at Albert Einstein College of Medicine and the Director, Montefiore Headache Center commented “The SAMURAI study was successful from the twin perspectives of efficacy and tolerability. The treatment effects, even in patients with high levels of headache related disability, are impressive. The inclusion of patients with cardiovascular conditions and risk factors makes the safety profile compelling. Lasmiditan has the potential to become an important treatment option, particularly for migraine patients at high risk for cardiovascular disease. In these patients, available acute migraine treatments such as triptans and ergot alkaloids may be contraindicated or have precautions and warnings because of their vasoconstrictive effects.”
“We have shown in SAMURAI that lasmiditan was effective in the acute treatment of migraine and well tolerated,” said Thomas P. Mathers, President and Chief Executive Officer of CoLucid. “The study demographics represented the largest group of patients diagnosed and treated for migraine in the United States: primarily women over the age of 40. Most patients, regardless of gender, had either CVRF or cardiovascular conditions. Currently, the use of prescription drug treatments in general, and triptans specifically, is less in these patients as compared to migraine patients with no CVRF. Given the convincing nature of the data, we are eager to complete the ongoing SPARTAN pivotal clinical trial, which uses the same endpoints and same statistical powering.”
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 2H/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 the Company’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.
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 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.
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.
Source: CoLucid Pharmaceuticals, Inc.
Posted: September 2016