REYVOW® (lasmiditan) C-V Demonstrated Superior Pain Freedom At 2 Hours in At Least 2 of 3 Migraine Attacks in New Phase 3 Consistency of Effect Study
"Healthcare professionals, advocacy groups and people with migraine have made it clear that one of the most important things they want from an acute treatment is consistent efficacy during the first and subsequent attacks," said
The CENTURION study assessed REYVOW's efficacy and safety, including consistency of response, in the acute treatment of migraine for adults, with or without aura, across four attacks. In the trial, 1,471 people with migraine were randomized and treated with either REYVOW 200 mg (n=486), REYVOW 100 mg (n=485) or control treatment (placebo for some but not all attacks, n=500) per attack. Study participants treated a migraine attack when their pain was at least of moderate severity and within 4 hours after pain onset. This international trial included patients from
CONSISTENCY OF PAIN FREEDOM AND PAIN RELIEF AT 2 HOURS
Pain freedom and pain relief, respectively, are defined as a reduction of pain at baseline to no pain, and headache pain that reduced to mild or resolved completely.
Study results show that people taking REYVOW 200 mg had 7.2 times greater odds of achieving pain freedom at 2 hours in at least 2 of 3 migraine attacks (co-primary endpoint) than those on placebo (24.4% vs. 4.3%; odds ratio: 7.2; p<0.001), with a therapeutic gain of approximately 20%. People who took REYVOW 100 mg had 3.8 times greater odds of achieving pain freedom at 2 hours in at least 2 of 3 attacks than study participants on placebo (14.4% vs. 4.3%; p<0.001), translating to a therapeutic gain for patients taking REYVOW of approximately 10%.
Nearly 2 out of 3 people taking REYVOW achieved pain relief at 2 hours in at least 2 of 3 attacks, including 66.7% and 62.3% of those taking REYVOW 200 mg and 100 mg, respectively, compared to 36.9% of those on placebo (p<0.001 for each REYVOW comparison to placebo).
CONSISTENCY OF PAIN FREEDOM AND PAIN RELIEF AT 2 HOURS IN GROUP WITH PRIOR TRIPTAN HISTORY
The study also assessed pain freedom and pain relief at 2 hours in at least 2 of 3 migraine attacks in subsets of participants who had previously tried triptans that were ineffective, intolerable or became contraindicated. These outcomes were non-gated secondary endpoints.
Significantly greater proportions of people taking REYVOW were pain-free at 2 hours in at least 2 of 3 migraine attacks (20.1% for REYVOW 200 mg and 11.0% for REYVOW 100 mg), compared to placebo (4.3%) (p<0.001 for each REYVOW comparison to placebo). Nearly 2 out of 3 persons taking REYVOW 200 mg (62.7%) and more than half of participants taking 100 mg (55.6%) achieved pain relief at 2 hours in at least 2 of 3 migraine attacks compared to 1 out of 3 patients (33.6%) on placebo (p<0.001 for each REYVOW comparison to placebo).
"In this study, people taking REYVOW, who had previously tried triptans that were ineffective, intolerable or contraindicated, achieved significantly greater pain freedom and pain relief at 2 hours across multiple attacks compared to those taking placebo," said
Observed safety findings in the CENTURION study were generally consistent with those seen in previous REYVOW clinical trials. The most frequent treatment-emergent adverse events (TEAEs) seen for REYVOW (≥2% in either dose group) over all four attacks were dizziness, paresthesia (tingling), fatigue, nausea, vertigo (sensation of spinning or movement), somnolence (sleepiness), hypoesthesia (diminished sensation), muscle weakness, asthenia (abnormal physical weakness) and feeling abnormal. The incidence of TEAEs was highest during the first attack.
"Among recently approved novel medications for the acute treatment of migraine, REYVOW is the first and only to be evaluated in a consistency study. Additionally, CENTURION is one of the only studies of an FDA-approved acute treatment for migraine to compare the consistency of efficacy against placebo," said
ABOUT REYVOW® (lasmiditan) TABLETS
REYVOW is a novel oral medication that strongly binds to 5-HT1F receptors located both centrally and peripherally, which may play a role in migraine, a neurologic disease. REYVOW is approved for the acute treatment of migraine with or without aura in adults and is not indicated for the preventive treatment of migraine. REYVOW, the first and only FDA-approved ditan, is brain-penetrant and presumably exerts its therapeutic effects by activating these receptors; however, the precise mechanism is unknown.
IMPORTANT SAFETY INFORMATION FOR REYVOW
WARNINGS AND PRECAUTIONS
REYVOW may cause significant driving impairment. In a driving study, administration of single 50 mg, 100 mg, or 200 mg doses of REYVOW significantly impaired subjects' ability to drive. Additionally, more sleepiness was reported at 8 hours following a single dose of REYVOW compared to placebo. Advise patients not to engage in potentially hazardous activities requiring complete mental alertness, such as driving a motor vehicle or operating machinery, for at least 8 hours after each dose of REYVOW. Patients who cannot follow this advice should not take REYVOW. Prescribers and patients should be aware that patients may not be able to assess their own driving competence and the degree of impairment caused by REYVOW.
Central Nervous System Depression
REYVOW may cause central nervous system (CNS) depression, including dizziness and sedation. Because of the potential for REYVOW to cause sedation, other cognitive and/or neuropsychiatric adverse reactions, and driving impairment, REYVOW should be used with caution if used in combination with alcohol or other CNS depressants. Patients should be warned against driving and other activities requiring complete mental alertness for at least 8 hours after REYVOW is taken.
In clinical trials, reactions consistent with serotonin syndrome were reported in patients treated with REYVOW who were not taking any other drugs associated with serotonin syndrome. Serotonin syndrome may also occur with REYVOW during coadministration with serotonergic drugs [e.g., selective serotonin reuptake inhibitors (SSRIs), serotonin norepinephrine reuptake inhibitors (SNRIs), tricyclic antidepressants (TCAs), and monoamine oxidase (MAO) inhibitors]. Serotonin syndrome symptoms may include mental status changes (e.g., agitation, hallucinations, coma), autonomic instability (e.g., tachycardia, labile blood pressure, hyperthermia), neuromuscular signs (e.g., hyperreflexia, incoordination), and/or gastrointestinal signs and symptoms (e.g., nausea, vomiting, diarrhea). The onset of symptoms usually occurs within minutes to hours of receiving a new or a greater dose of a serotonergic medication. Discontinue REYVOW if serotonin syndrome is suspected.
Medication Overuse Headache
Overuse of acute migraine drugs (e.g., ergotamines, triptans, opioids, or a combination of drugs for 10 or more days per month) may lead to exacerbation of headache (i.e., medication overuse headache). Medication overuse headache may present as migraine-like daily headaches or as a marked increase in frequency of migraine attacks. Detoxification of patients including withdrawal of the overused drugs and treatment of withdrawal symptoms (which often includes a transient worsening of headache) may be necessary.
The most common adverse reactions associated with REYVOW (≥2% and greater than placebo in clinical studies) were dizziness, fatigue, paresthesia, sedation, nausea and/or vomiting, and muscle weakness.
DRUG ABUSE AND DEPENDENCE
REYVOW contains lasmiditan, a Schedule V controlled substance.
In a human abuse potential study in recreational poly-drug users (n=58), single oral therapeutic doses (100 mg and 200 mg) and a supratherapeutic dose (400 mg) of REYVOW were compared to alprazolam (2 mg) (C-IV) and placebo. With all doses of REYVOW, subjects reported statistically significantly higher "drug liking" scores than placebo, indicating that REYVOW has abuse potential. Subjects who received REYVOW reported statistically significantly lower "drug liking" scores than alprazolam. Euphoric mood occurred to a similar extent with REYVOW 200 mg, REYVOW 400 mg, and alprazolam 2 mg (43-49%). A feeling of relaxation was noted in more subjects on alprazolam (22.6%) than with any dose of REYVOW (7-11%). Phase 2 and 3 studies indicate that, at therapeutic doses, REYVOW produced adverse events of euphoria and hallucinations to a greater extent than placebo. However, these events occur at a low frequency (about 1% of patients). Evaluate patients for risk of drug abuse and observe them for signs of lasmiditan misuse or abuse.
Physical withdrawal was not observed in healthy subjects following abrupt cessation after 7 daily doses of lasmiditan 200 mg or 400 mg.
LM HCP ISI 11JAN2020
Migraine is a severely disabling neurologic disease characterized by recurrent episodes of moderate to severe headache accompanied by other symptoms including nausea, sensitivity to light, and sensitivity to sound. More than 30 million American adults have migraine, with three times more women than men affected by migraine. Migraine is often incapacitating, leading to high personal, societal and economic burden. According to the
For over 25 years,
This press release contains forward-looking statements (as that term is defined in the Private Securities Litigation Reform Act of 1995) about REYVOW (lasmiditan) as a treatment for patients with migraine and reflects
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