INDIANAPOLIS, Oct. 6, 2020 /PRNewswire/ -- Adults who took
REYVOW® (lasmiditan) C-V for their migraine attacks at
doses of 100 mg or 200 mg had 3.8 and 7.2 times greater odds,
respectively, of achieving superior pain freedom at 2 hours post
treatment compared to those taking placebo in at least 2 out of 3
attacks (co-primary endpoint), new findings from the recently
completed Phase 3 study CENTURION reveal. This co-primary endpoint
result translated to therapeutic gains, or differences between
REYVOW and placebo groups, of approximately 10-20%. Moreover, in at
least 2 out of 3 attacks, Eli Lilly and Company's (NYSE: LLY)
REYVOW demonstrated superiority over placebo in pain relief at 2
hours. In addition, significantly more study participants who
treated their migraine attacks with REYVOW achieved pain freedom
and pain relief at 2 hours in 2 out of 3 attacks with REYVOW versus
those on placebo, even if they had previously tried triptans that
were ineffective, intolerable or became contraindicated. As
previously reported, REYVOW demonstrated superiority over placebo
in all of the study's 18 gated endpoints. Study investigator Dr.
Messoud Ashina, M.D., professor of neurology, Danish Headache
Center and Dept. of Neurology, University of
Copenhagen, Copenhagen,
Denmark and Dr. Uwe Reuter,
M.D., Ph.D., professor of neurology, Charite University Hospital of
Berlin, Berlin, Germany, are presenting these results
and answering questions virtually at the 18th Migraine Trust
International Symposium (MTIS 2020), during a session on
Oct. 7th, 4:45 –
5:45 p.m. CEDT/10:45 – 11:45 a.m.
EDT.
"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 Mark
Mintun, M.D., vice president of pain and neurodegeneration,
Eli Lilly and Company. "Not being able to rely on their migraine
treatment causes frustration and disappointment when their medicine
doesn't work consistently. We are excited about the latest findings
from the CENTURION trial. We believe that REYVOW's therapeutic gain
of up to 20% and up to 7.2 times greater odds of achieving pain
freedom at 2 hours in at least 2 out of 3 attacks with the 200 mg
dose are meaningful for patients and healthcare providers who seek
consistency as a goal with acute medications when treating migraine
attacks."
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 Austria, Belgium, China, Czechia, Denmark, France, Germany, Hungary, India, Italy,
Mexico, Netherlands, Russian
Federation, Spain,
Switzerland, United Kingdom and the United States of America. Co-primary
efficacy endpoints were pain freedom at 2 hours for the first
attack, and pain freedom at 2 hours for at least 2 of 3 attacks.
Secondary endpoints included pain relief at 2 hours after the first
attack and in at least 2 of 3 attacks and findings in the subset of
study participants who had previously tried triptans that were
ineffective, intolerable or became contraindicated in treating
their migraine attacks. Patients entered results into an electronic
diary at 30 minutes, 60 minutes, as well as 2, 4, 6, 24 and 48
hours after dosing. All of the study's treatment comparisons were
prespecified, and 18 endpoints were gated, meaning they were set
before the study ended and each comparison was reviewed separately
in a specified order to verify the accuracy of the study
results.
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 Dr. Ashina. "These latest findings are encouraging news for
patients and their healthcare providers when discussing
personalized treatment goals such as consistency of response.
Migraine attacks can be debilitating so it's imperative patients
have acute treatment options that can help them achieve the
outcomes that matter to them."
SAFETY FINDINGS
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 Ilya Yuffa, president of Lilly Bio-Medicines.
"We are delighted that REYVOW demonstrated consistent and superior
efficacy across multiple migraine attacks compared to placebo.
These are meaningful insights for patients and their healthcare
providers, and we look forward to sharing the findings with health
regulatory authorities in Europe,
Japan and China."
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
Driving Impairment
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.
Serotonin Syndrome
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.
ADVERSE REACTIONS
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.
Abuse
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.
Dependence
Physical withdrawal was not observed in healthy subjects
following abrupt cessation after 7 daily doses of lasmiditan
200 mg or 400 mg.
See Full Prescribing Information and
Medication Guide.
LM HCP ISI 11JAN2020
About Migraine
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 Medical
Expenditures Panel Survey, total annual healthcare costs associated
with migraine are estimated to be as high as $56 billion in the
United States, yet it remains under-recognized and
under-treated.
About Lilly's Commitment to Headache Disorders
For over 25 years, Lilly has been committed to helping people
affected by headache disorders, investigating more than a dozen
different compounds for the treatment of migraine and cluster
headache. These research programs have accelerated our
understanding of these diseases and furthered the advancement of
treatments for headache disorders including REYVOW, approved by the
FDA for the acute treatment of migraine, with or without aura, in
adults. Our goal is to apply our combined clinical, academic and
professional experience to build a research portfolio that delivers
broad solutions and addresses the needs of people affected by these
disabling neurologic diseases.
About Eli Lilly and Company
Lilly is a global health care leader that unites caring with
discovery to create medicines that make life better for people
around the world. We were founded more than a century ago by a man
committed to creating high-quality medicines that meet real needs,
and today we remain true to that mission in all our work. Across
the globe, Lilly employees work to discover and bring life-changing
medicines to those who need them, improve the understanding and
management of disease, and give back to communities through
philanthropy and volunteerism. To learn more about Lilly, please
visit us at lilly.com and lilly.com/newsroom. P-LLY
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 Lilly's current beliefs. Among other things,
there is no guarantee that future study results will be consistent
with study findings to date, that REYVOW will receive additional
regulatory approvals, or that REYVOW will be commercially
successful. For further discussion of these and other risks and
uncertainties, see Lilly's Form 10-K and Form 10-Q filings with the
United States Securities and Exchange Commission. Except as
required by law, Lilly undertakes no duty to update forward-looking
statements to reflect events after the date of this release.
© Lilly USA, LLC 2020. All
rights reserved
Refer
to: Jen
Dial; dial_jennifer_kay@lilly.com; 317-220-1172 (Lilly
Bio-Medicines)
Kevin
Hern; hern_kevin_r@lilly.com; 317-277-1838 (Investor
Relations)
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