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Headache Disorders
Published in Sahar Swidan, Matthew Bennett, Advanced Therapeutics in Pain Medicine, 2020
In recent years, four monoclonal antibodies targeting CGRP or the CGRP receptor have been tested in humans for the prevention of migraine: galcanezumab, eptinezumab, erenumab, and fremanezumab.31 High-quality RCTs have demonstrated the efficacy of these antibodies in decreasing migraine days in episodic migraine as well as chronic migraine. Fremanezumab showed efficacy in reducing monthly migraines in a phase III trial of 1130 patients with chronic migraine.32 Erenumab—the only monoclonal antibody that targets the CGRP receptor—demonstrated similar efficacy for episodic migraine in addition to chronic migraine.33 The reported reduction in monthly migraine has been approximately three to six episodes per month and significantly greater than placebo. Of note, patients with chronic migraine were excluded from the previously cited studies if they had failed preventative treatment with two to three prophylactic medications. Despite the promising results of these positive trials, additional studies are needed to determine the long-term efficacy, safety, and cost-effectiveness of monoclonal antibodies. An analysis of a 5-year study of erenumab revealed sustained treatment effect and safety at week 64, with 25% of patients reporting 100% reduction in monthly migraine days.34 Erenumab, galcanezumab, and fremanezumab are all currently FDA-approved for migraine prevention. The long-term safety is still questioned, as well as the role of these agents as first-line treatments or only after multiple medications failures. As CGRP is an essential vasodilatory protein for cerebral and coronary arteries, its potential contraindication in patients with coronary artery disease, past stroke, or uncontrolled hypertension for example has not been well-studied but should be taken into consideration when there is a thought of prescribing these agents.
Treatment of migraine with monoclonal antibodies
Published in Expert Opinion on Biological Therapy, 2022
José María Serra López-Matencio, Ana Beatriz Gago-Veiga, Manuel Gómez, Estefanía Alañón Plaza, Gina Paola Mejía, Miguel Ángel González-Gay, Santos Castañeda
Fremanezumab, galcanezumab and eptinemzumab, bind directly to CGRP, unlike erenumab which is the only one that acts by blocking the CGRP receptor (Table 1). Because of their composition and large molecular size, mAbs have a limited ability to cross the BBB, therefore, their mechanism of action is not by direct action in the brain parenchyma but via the trigeminal ganglion and its distal terminals in the dura and pia mater. They are administered subcutaneously (erenumab, galcanezumab and fremanezumab) and intravenously (epinetezumab). The long half-life of fremanezumab allows both, a dosing interval of 3 months, as in the case of eptinezumab, and a 28–30 days dosing interval, as in the case of erenumab and galcanezumab (Table 1). This low frequency of administration in relation to classic migraine preventive treatments, which require daily oral administration, would facilitate adherence to treatment. Doses of erenumab (70 mg or 140 mg), galcanezumab (120 mg) and fremanezumab (225 mg) are available in auto-injectable form for subcutaneous administration in the anterior thighs, abdomen or arm. The first application of these drugs is recommended to be performed by the physician or by a specialized nurse to instruct the patient on their use and to assess initial tolerance. Eptinezumab requires intravenous infusion.
Antibodies to watch in 2018
Published in mAbs, 2018
Hélène Kaplon, Janice M. Reichert
Eptinezumab (ALD403), an IgG1 mAb targeting calcitonin gene-related peptide (CGRP), is being evaluated for migraine prevention. In June 2017, Alder BioPharmaceuticals announced that the primary and key secondary endpoints were met in the placebo-controlled Phase 3 PROMISE 1 study (NCT02559895), which evaluated the effects of eptinezumab in patients with frequent episodic migraine.52 Patients enrolled in the study experienced, on average, 8.6 migraines days per month. They received 300 mg, 100 mg, or 30 mg doses of eptinezumab or placebo during the study; results from the 30 mg dose level were not included in the statistical analysis plan. Statistically significant reductions in monthly migraine days from baseline over weeks 1 through 12 were observed for both the 300 mg and 100 mg doses (4.3 monthly migraine days for 300 mg (p = 0.0001) and 3.9 days for 100 mg (p = 0.0179) compared to an average 3.2 days for placebo). Approximately 1/3 of patients achieved a ≥75% reduction in migraine days through 4 and 12 weeks, and an average of 1 in 5 patients had no migraines in any given month from months 1 through 6.
Combining two CGRP inhibitors to treat migraine
Published in Expert Opinion on Drug Safety, 2022
A fairly new class used in the treatment of migraine is the calcitonin gene-related peptide (CGRP) inhibitors. CGRP is a peptide involved in migraine attacks, and decreases in this neuropeptide is associated with antimigraine effectiveness [1]. There are two types of CGRP inhibitors: monoclonal antibodies (mAbs) and gepants. The US Food and Drug Administration has initially approved four mAbs targeting the CGRP peptide or its receptor for the prophylactic treatment of migraine. Erenumab, fremanezumab, and galcanezumab are subcutaneous injections usually used once a month. Eptinezumab is an intravenous formulation that is given every three months. The four mAbs have proven to be of similar efficacy and, in general, with fewer risks of adverse events than traditional oral medications [2]. However, only very few patients are attack free when assuming a CGRP-targeted mAb [3,4]. A new class of oral CGRP receptor antagonists has more recently entered the pharmaceutical market, which include ubrogepant, rimegepant, and atogepant. Gepants are an unofficial name for these medications, that are effective at both relieving migraines and preventing them [5,6]. Now that gepants are available, patients with insufficient response from CGRP-targeted mAbs may benefit from coadministration. Combining two drugs from the same class is nevertheless dangerous, doubling up the risk or severity of side effects. Using two CGRP inhibitors in a single individual could broad the interference with the physiological CGRP and cause harm. We currently do not know whether gepants are safe and will provide any treatment benefits in patients receiving CGRP-targeted mAbs.