Eptinezumab in episodic migraine: A randomized, double-blind, placebo-controlled study (PROMISE-1)

Ashina, Messoud; Saper, Joel R.; Cady, Roger; Schaeffler, Barbara; Biondi, David; Hirman, Joe; Pederson, Susan; Allan, Brent; Smith, Jeff

doi:10.1177/0333102420905132

Cited by 266 publications

(404 citation statements)

References 31 publications

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“…Thus, we urge providers to first consult the American Academy of Neurology/American Headache Society Guidelines (last published in 2012 45 ; new ones are currently being produced) and to re‐evaluate patients' responses to the medications listed in those guidelines. In addition, therapies which have been demonstrated to be beneficial since the development of that guideline include: CGRP and CGRP receptor antagonist monoclonal antibodies (mAbs) : In the past 2 years, mAbs against CGRP or the CGRP receptor have been FDA approved for preventive treatment of both episodic and chronic migraine – erenumab‐aooe, 46‐48 galcanezumab‐gnlm, 49‐51 fremanezumab‐vfrm, 52,53 and eptinezumab‐jjmr 54,55 . The first 3 are intended for self‐injection at home, with detailed instructions available for each product on its website. Angiotensin‐converting enzyme (ACE) inhibitors/angiotensin receptor blockers (ARBs) : Candesartan 56,57 now has evidence of efficacy and good tolerability in migraine prevention, 58,59 and lisinopril 56,60 was considered “possibly effective” in the 2015 guideline.…”

Section: Introductionmentioning

confidence: 99%

Migraine Care in the Era of COVID‐19: Clinical Pearls and Plea to Insurers

et al. 2020

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Objective.-To outline strategies for the treatment of migraine which do not require in-person visits to clinic or the emergency department, and to describe ways that health insurance companies can remove barriers to quality care for migraine.Background.-COVID-19 is a global pandemic causing widespread infections and death. To control the spread of infection we are called to observe "social distancing" and we have been asked to postpone any procedures which are not essential. Since procedural therapies are a mainstay of headache care, the inability to do procedures could negatively affect our patients with migraine. In this manuscript we review alternative therapies, with particular attention to those which may be contra-indicated in the setting of COVID-19 infection.Design/Results.-The manuscript reviews the use of telemedicine visits and acute, bridge, and preventive therapies for migraine. We focus on evidence-based treatment where possible, but also describe "real world" strategies which may be tried. In each section we call out areas where changes to rules from commercial health insurance companies would facilitate better migraine care.Conclusions.-Our common goal as health care providers is to maximize the health and safety of our patients. Successful management of migraine with avoidance of in-person clinic and emergency department visits further benefits the current urgent societal goal of maintaining social distance to contain the COVID-19 pandemic.

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Section: Introductionmentioning

confidence: 99%

Migraine Care in the Era of COVID‐19: Clinical Pearls and Plea to Insurers

et al. 2020

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“…Renal function was normal in 55.3% of patients/subjects, with mild or moderate decreases in estimated glomerular filtration rate (eGFR) in 41.9% and 2.7% of patients/subjects, respectively. The average MMD during the screening period of studies CLIN‐005, CLIN‐006, and CLIN‐011 was approximately 14 days (CLIN‐005, 16.5 MMD; CLIN‐006, 8.7 MMD; CLIN‐011, 16.1 MMD).…”

Section: Resultsmentioning

confidence: 99%

“…PK parameters from the final population PK model were used to derive exposure metrics: area under the curve from time 0 to 12 weeks (AUC 0‐12wk ), maximum concentration ( C max ), average concentration ( C avg ), and trough concentration ( C trough ). The exposure‐response relationship of plasma eptinezumab was evaluated using these single‐dose exposure parameters and the change in frequency of MMD (weeks 1‐12) from studies CLIN‐005, CLIN‐006, and CLIN‐011 . A saturable inhibitory maximum‐effect ( E max ) model was used to assess relationships between the exposure metrics of eptinezumab and the reduction in MMD.…”

Section: Methodsmentioning

confidence: 99%

“…Eptinezumab (ALD403) is a humanized anti‐CGRP antibody with an IgG1 backbone that binds to both the α and β forms of CGRP and is currently under development for migraine prevention. In controlled clinical studies, it has demonstrated efficacy compared to placebo in the prevention of migraine in patients with episodic migraine (EM) and chronic migraine (CM) . This report describes a population PK modeling analysis conducted for the IV administration of eptinezumab at single doses of 10‐1000 mg in healthy subjects and in patients with EM and CM from eight studies in the eptinezumab clinical program .…”

Section: Introductionmentioning

confidence: 99%

“…In controlled clinical studies, it has demonstrated efficacy compared to placebo in the prevention of migraine in patients with episodic migraine (EM) and chronic migraine (CM) . This report describes a population PK modeling analysis conducted for the IV administration of eptinezumab at single doses of 10‐1000 mg in healthy subjects and in patients with EM and CM from eight studies in the eptinezumab clinical program . A further goal was to assess the dose‐ and exposure‐response relationships of selected endpoints in patients with EM and CM who received eptinezumab.…”

Section: Introductionmentioning

confidence: 99%

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Population pharmacokinetic and exposure‐response analysis of eptinezumab in the treatment of episodic and chronic migraine

Baker

Schaeffler

Béliveau³

et al. 2020

Pharmacology Res & Perspec

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Eptinezumab is a humanized mAb that targets calcitonin gene‐related peptide and is under regulatory review for the prevention of episodic and chronic migraine (EM, CM). It is important to determine whether exposures achieved with intravenous (IV) administration of eptinezumab achieve desired pharmacologic effects. Population pharmacokinetics, including dose‐ and exposure‐response analyses, were performed using patient‐level data from the eptinezumab clinical trial program with IV doses ranging from 10 to 1000 mg in pharmacokinetic analyses or 10 to 300 mg in phase 2/3 clinical studies in patients with EM or CM. Exposure‐response analysis explored the relationship between eptinezumab exposure metrics and efficacy parameters including monthly migraine days. The pharmacokinetic profile of eptinezumab was characterized by rapid attainment of maximum plasma concentration (ie, end of IV administration) and a terminal half‐life of 27 days. Covariate analysis found that patient characteristics had no clinically significant effects on pharmacokinetic parameters and were insufficient to influence dosing. Dose‐ and exposure‐response analyses found exposure with single doses ≥100 mg was associated with greater efficacy compared with doses ≤30 mg and a plateau of effect between 100 and 300 mg. A saturable inhibitory Emax model found the exposure over 12 weeks produced by single‐dose eptinezumab 100 and 300 mg exceeded the exposure estimates required to achieve 90% of the maximal efficacy (EC90). This pharmacokinetic analysis of eptinezumab supports dosing every 12 weeks with no adjustment for patient characteristics, including exposures associated with 100‐ or 300‐mg doses producing optimal efficacy effects. The similar efficacy profiles support 100 mg as the lowest effective dose of eptinezumab.

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Diagnosis and Management of Headache

Robbins

2021

JAMA

116

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IMPORTANCE Approximately 90% of people in the US experience headache during their lifetime. Migraine is the second leading cause of years lived with disability worldwide.OBSERVATIONS Primary headache disorders are defined as headaches that are unrelated to an underlying medical condition and are categorized into 4 groups: migraine, tension-type headache, trigeminal autonomic cephalalgias, and other primary headache disorders. Studies evaluating prevalence in more than 100 000 people reported that tension-type headache affected 38% of the population, while migraine affected 12% and was the most disabling. Secondary headache disorders are defined as headaches due to an underlying medical condition and are classified according to whether they are due to vascular, neoplastic, infectious, or intracranial pressure/volume causes. Patients presenting with headache should be evaluated to determine whether their headache is most likely a primary or a secondary headache disorder. They should be evaluated for symptoms or signs that suggest an urgent medical problem such as an abrupt onset, neurologic signs, age 50 years and older, presence of cancer or immunosuppression, and provocation by physical activities or postural changes. Acute migraine treatment includes acetaminophen, nonsteroidal anti-inflammatory drugs, and combination products that include caffeine. Patients not responsive to these treatments may require migraine-specific treatments including triptans (5-HT 1B/D agonists), which eliminate pain in 20% to 30% of patients by 2 hours, but are accompanied by adverse effects such as transient flushing, tightness, or tingling in the upper body in 25% of patients. Patients with or at high risk for cardiovascular disease should avoid triptans because of vasoconstrictive properties. Acute treatments with gepants, antagonists to receptors for the inflammatory neuropeptide calcitonin gene-related peptide, such as rimegepant or ubrogepant, can eliminate headache symptoms for 2 hours in 20% of patients but have adverse effects of nausea and dry mouth in 1% to 4% of patients. A 5-HT 1F agonist, lasmiditan, is also available for acute migraine treatment and appears safe in patients with cardiovascular risk factors. Preventive treatments include antihypertensives, antiepileptics, antidepressants, calcitonin gene-related peptide monoclonal antibodies, and onabotulinumtoxinA, which reduce migraine by 1 to 3 days per month relative to placebo.CONCLUSIONS AND RELEVANCE Headache disorders affect approximately 90% of people during their lifetime. Among primary headache disorders, migraine is most debilitating and can be treated acutely with analgesics, nonsteroidal anti-inflammatory drugs, triptans, gepants, and lasmiditan.

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Eptinezumab in episodic migraine: A randomized, double-blind, placebo-controlled study (PROMISE-1)

Cited by 266 publications

References 31 publications

Migraine Care in the Era of COVID‐19: Clinical Pearls and Plea to Insurers

Migraine Care in the Era of COVID‐19: Clinical Pearls and Plea to Insurers

Population pharmacokinetic and exposure‐response analysis of eptinezumab in the treatment of episodic and chronic migraine

Diagnosis and Management of Headache

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