Lilly's Reyvow (Lasmiditan) Achieves Pain Freedom Within 1 Hour and Sustained Relief Up to 48 Hours in New Phase 3 CENTURION Study

September 13, 2020 News /Bio ValleyBIOON/ --Eli Lilly(Eli Lilly) recently at PAINWeek® 2020 live virtualConferenceThe results of CENTURION, a new Phase III clinical study evaluating Reyvow (lasmiditan) C-V tablets for the treatment of migraine attacks in adult patients, have been published. The study was recently completed, and the data showed that patients taking 100 mg or 200 mg of Reyvow were 3.8 and 4.6 times more likely, respectively, to achieve pain freedom at 2 hours post-dose compared with those receiving placebo (co-primary endpoints). Furthermore, Reyvow demonstrated superiority over placebo across all 18 gated endpoints, including pain freedom at 1 hour after treatment of the first migraine attack (200 mg dose), pain relief at 1 and 2 hours (both doses), sustained pain freedom at 24 hours (both doses) and 48 hours (200 mg dose), and the proportion of patients free from disability at 2 hours (both doses).

Reyvow is an oral prescription medication that was approved by the U.S. FDA in October 2019 for the acute treatment of migraine with or without aura in adults.Reyvow represents the first new class of acute migraine treatment approved by the FDA in over 20 years.This drug isFDAThe first approved 5-HT1F receptor agonist, which acts on both the central and peripheral nervous systems, has a mechanism of action distinct from other currently marketed acute migraine treatments. It is important to note that Reyvow is not indicated for the preventive treatment of migraine. The drug is available in 50 mg, 100 mg, and 200 mg strengths, allowing for flexible dosing as needed.

In clinical studies, a single dose of Reyvow rapidly and completely eliminated migraine pain and its most bothersome symptoms (nausea, photophobia, or phonophobia) within just 2 hours. United StatesFDAThe latest guidelines issued by the American Headache Society have raised clinical standards, recommending migraine medicationsClinical TrialThe efficacy must be demonstrated to eliminate pain and the most bothersome symptoms, rather than merely alleviating pain. Reyvow isFDAThe first acute migraine treatment drug approved to meet this new standard.

The CENTURION study evaluated the efficacy and safety of Reyvow for the acute treatment of migraine (with or without aura) in adults, including the consistency of treatment response across four attacks. In this study, 1,471 patients with migraine were randomized to receive at least one dose of Reyvow 200 mg (n=486), 100 mg (n=485), or control treatment (placebo for some but not all attacks, n=500) per attack. Patients treated migraine attacks when pain was at least moderate in intensity and within 4 hours of pain onset. The co-primary efficacy endpoints included pain freedom at 2 hours post-dose after the first attack, and pain freedom at 2 hours post-dose in two out of three attacks. Secondary endpoints included pain freedom at 1 hour, sustained pain freedom at 24 and 48 hours, and pain relief at 1 and 2 hours, among others. Patients recorded outcomes in an electronic diary at 30 minutes, 60 minutes, and 2, 4, 6, 24, and 48 hours post-dose. All treatment comparisons in the study were prespecified, and the 18 endpoints were gated, meaning they were established before the study concluded, and each comparison was reviewed separately in a specified order to verify the accuracy of the study results.

——Results of pain relief at 2 hours and 1 hour:Data showed that the odds of achieving pain freedom at 2 hours (co-primary endpoint) were 4.6 times higher in the Reyvow 200 mg group than in the placebo group (29.3% vs. 8.4%; odds ratio [OR] = 4.6; p < 0.001; therapeutic gain approximately 21%), and 3.8 times higher in the Reyvow 100 mg group than in the placebo group (25.8% vs. 8.4%; p < 0.001; therapeutic gain approximately 17%). These treatment effects reflect the differences between the Reyvow groups and the placebo group in the percentage of patients who were pain-free at 2 hours. For pain freedom at 1 hour, the odds were 7 times higher in the Reyvow 200 mg group than in the placebo group (12.7% vs. 2.0%; p < 0.001), and 3 times higher in the Reyvow 100 mg group than in the placebo group (6.0% vs. 2.0%).

Uwe Reuter, MD, PhD, Professor of Neurology at Charité – Universitätsmedizin Berlin in Germany, stated, “Migraine attacks affect patients in different ways, so it is important that patients have options to help achieve their individual treatment goals. I am highly encouraged by this study, in which we saw that Reyvow could help patients achieve pain freedom as early as 60 minutes after dosing, with effects lasting up to 48 hours.”

2. Reyvow was superior to placebo in patients with a history of prior triptan use, in terms of pain relief and freedom from disability.(Pain relief refers to a reduction in pain intensity to mild levels or complete resolution)

(1) Results of pain relief at 2 hours and 1 hour:Nearly two-thirds of patients treated with Reyvow achieved pain relief at 2 hours, with rates of 65.2% and 65.4% in the Reyvow 200 mg and 100 mg groups, respectively, compared to 41.3% in the placebo group (all p<0.001). At 1 hour, nearly half of the patients treated with Reyvow achieved pain relief, with rates of 47.2% in the Reyvow 20 mg group and 48.7% in the 100 mg group, compared to 29.3% in the placebo group (all p<0.001).

Among patients (n=579) for whom triptan therapy for acute migraine attacks had previously been ineffective, intolerable, or contraindicated, the proportion of patients achieving pain freedom at 2 hours was nearly three times higher in those treated with Reyvow (24.0% in the 100-mg group and 25.6% in the 200-mg group) than in those receiving placebo (8.8%).

Dr. Timothy R. Smith, President and CEO of StudyMetrix Research and an investigator in the study, stated, “In this study, patients treated with Reyvow demonstrated superior outcomes compared to those receiving placebo, including pain freedom, pain relief, absence of disability, and other important therapeutic endpoints following the initial migraine attack. This analysis is exciting given that migraines frequently disrupt daily life and so many patients require assistance in managing their debilitating migraine attacks.”

The safety results observed in the CENTURION study were generally consistent with those of previous ReyvowClinical TrialConsistent. During the study period, the incidence of serious treatment-emergent adverse events (TEAEs) was similar across treatment groups: Reyvow 200 mg group [n=2 (0.4%)], 100 mg group [n=1 (0.2%)], and placebo group [n=2 (0.4%)]. The most common TEAEs following treatment of the first attack (occurring in ≥2% of patients in either dose group during the first attack) included dizziness, paresthesia (tingling), fatigue, nausea, vertigo (sensation of spinning or motion), somnolence (drowsiness), hypoesthesia (reduced sensation), muscle weakness, asthenia (abnormal physical weakness), and dysesthesia.

Senior Vice President of Eli Lilly and CompanyEli LillyPatrik Jonsson, President of the Biopharmaceutical Company, stated, “We are excited about the insights into Reyvow derived from the well-designed CENTURION study, including its significant efficacy in achieving pain freedom within 2 hours, and we look forward to sharing consistent results at the 18th Migraine Trust International Symposium (MTIS 2020), to be held next month from October 3–9. This holds significant importance for healthcare providers and their patients when making critical treatment decisions for migraine attacks.”

Migraine is a common chronic neurovascular disorder characterized by recurrent, severe headaches, typically unilateral. Currently, there is no medication that can cure migraine. The World Health Organization (WHO) has listed migraine as one of the top 10 most disabling diseases worldwide.

Reyvow’s active pharmaceutical ingredient is lasmiditan, an oral, centrally penetrating, selective serotonin 1F (5-HT1F) receptor agonist that is structurally and mechanistically distinct from currently approved migraine medications and lacks vasoconstrictive activity. Notably, lasmiditan is the first and only “ditan”-class drug molecule approved for the acute treatment of migraine in adults. This approval represents the first major innovation in acute migraine therapy in more than two decades.

As with other drugs possessing central nervous system (CNS) activity, the FDA requires abuse potential studies for Reyvow. Abuse potential refers to the likelihood that a specific drug product or substance with CNS activity will be abused. Compared withFDAconsistent with the guidelines,Eli LillyA human abuse potential assessment was conducted; as part of the evaluation, Reyvow at therapeutic doses was associated with less drug liking compared to alprazolam, but more than placebo. (Bioon.com)

Original Source: REYVOW™ (lasmiditan) C-V Demonstrated Pain Freedom from Migraine Attacks At 60 Minutes and Up to 48 Hours in New Phase 3 Study