We consider five new therapeutic agents in this review, the first in a series of articles on new medications marketed in 2020 (see table on page 50): lasmiditan hemisuccinate (Reyvow–Lilly), ubrogepant (Ubrelvy–Allergan), rimegepant sulfate (Nurtec ODT–Biohaven), eptinezumab-jjmr (Vyepti–Lundbeck), and lemborexant (Dayvigo–Eisai). Following our review of each new therapeutic agent, we compare the new drug with the older medication(s) with which it is most similar in properties and uses. Advantages and disadvantages are identified at the time the new drug is first marketed and do not reflect approval of additional new drugs and/or changes that occur after the drug is initially marketed. Migraine affects an estimated 37 million people in the United States and is three times more common in women than in men. Characterized by throbbing pain in one area of the head and additional symptoms such as nausea, vomiting, and sensitivity to light (photophobia) and sound (phonophobia), migraine attacks range from mild to severe in intensity. Approximately one-third of individuals who suffer from migraine experience aura—a sensory phenomenon and/or visual disturbances—shortly before the migraine attack. Migraine may be relatively mild or brief but sufficiently severe, persistent, or frequent to become disabling with respect to working and fulfilling other responsibilities. A nonopioid analgesic such as an NSAID (e.g., ibuprofen) may be effective in relieving pain in patients with mild to moderate migraine. For patients with moderate to severe migraine, a triptan (serotonin 1B/1D [5-HT1B/1D]) receptor agonist is the usual treatment of choice, and pain freedom is experienced by up to 40% of patients within 2 hours following oral administration. All the triptans—almotriptan, eletriptan, frovatriptan, naratriptan, rizatriptan, sumatriptan, and zolmitriptan—are available in orally administered formulations. Sumatriptan and zolmitriptan are also available in formulations for nasal administration, and sumatriptan is available in a formulation for S.C. injection. Because the triptans increase the risk of complications in patients with certain cardiovascular disorders, their use is contraindicated in patients with these conditions. Other medications used to treat migraine include dihydroergotamine in formulations for S.C. or nasal administration and ergotamine in combination with caffeine (e.g., Cafergot–Sandoz) in formulations for oral or rectal administration. These agents also have potentially serious risks, and dosage recommendations must be strictly observed. Overuse of acute migraine drugs (i.e., use of triptans, ergotamines, opioids, or a combination of these drugs for 10 or more days per month) may result in exacerbation of headache (i.e., medication overuse headache) that presents as migraine-like daily headaches or as a marked increase in the frequency of migraine attacks. Detoxification of patients, including withdrawing the overused drugs and treating withdrawal symptoms (e.g., a transient worsening of headache) may be necessary. In the following sections, we review the properties and uses of three new drugs marketed in early 2020 for acute treatment of migraine in adults. Learning objectivesAt the conclusion of this knowledge-based activity, pharmacists will be able to ▪Identify the new therapeutic agents and explain their appropriate use.▪Identify the indications and mechanisms of action of the new agents.▪Identify the most important adverse events and other risks of the new therapeutic agents.▪State the route of administration for each new drug and the most important considerations for dosage and administration.▪Compare the new therapeutic agents with older medications to which they are most similar in properties and/or use, and identify the most important advantages and disadvantages of the new drugs. Preassessment questionsBefore participating in this activity, test your knowledge by answering the following questions. These questions will also be part of the CPE assessment. 1.Which of the following agents is associated with the occurrence of cataplexy-like symptoms? a.Rimegepantb.Eptinezumabc.Lemborexantd.Lasmiditan2.Which of the following statements is correct about ubrogepant? a.It is classified as an orexin receptor antagonist.b.It has been demonstrated to be more effective than triptans in treatment of migraine.c.It is available in tablet and nasal spray formulations.d.Concurrent use with a strong CYP3A4 inhibitor is contraindicated. At the conclusion of this knowledge-based activity, pharmacists will be able to ▪Identify the new therapeutic agents and explain their appropriate use.▪Identify the indications and mechanisms of action of the new agents.▪Identify the most important adverse events and other risks of the new therapeutic agents.▪State the route of administration for each new drug and the most important considerations for dosage and administration.▪Compare the new therapeutic agents with older medications to which they are most similar in properties and/or use, and identify the most important advantages and disadvantages of the new drugs. Before participating in this activity, test your knowledge by answering the following questions. These questions will also be part of the CPE assessment. 1.Which of the following agents is associated with the occurrence of cataplexy-like symptoms? a.Rimegepantb.Eptinezumabc.Lemborexantd.Lasmiditan2.Which of the following statements is correct about ubrogepant? a.It is classified as an orexin receptor antagonist.b.It has been demonstrated to be more effective than triptans in treatment of migraine.c.It is available in tablet and nasal spray formulations.d.Concurrent use with a strong CYP3A4 inhibitor is contraindicated. Lasmiditan hemisuccinate (Reyvow–Lilly) is a serotonin 1F (5-HT1F) receptor agonist that has a more selective action than the triptans, and its use has not been associated with vasoconstrictive effects. It is administered orally for acute treatment of migraine with or without aura in adults. Lasmiditan was evaluated in two placebo-controlled trials in which efficacy was established by an effect on pain freedom at 2 hours and most bothersome symptom ([MBS] e.g., photophobia, nausea) freedom at 2 hours. With a 100-mg dose of lasmiditan, 28% and 31% of patients were pain free at 2 hours, compared with 15% and 21%, respectively, of those receiving placebo. Forty-one percent and 44% of patients treated with lasmiditan were MBS free at 2 hours, compared with 30% and 33%, respectively, of those receiving placebo. The new drug has not been directly compared with triptans in clinical studies, and there are no data to suggest that it is more effective than the triptans. Lasmiditan may be an effective and safer alternative for patients with migraine who would be at greater risk of complications of underlying cardiovascular and other vascular disorders with use of a triptan. The most frequently reported adverse events in the clinical studies included dizziness (15%), paresthesia (7%), sedation (6%), and fatigue (5%). Because of its central nervous system (CNS) depressant action, patients treated with lasmiditan should be advised to not drive or operate machinery until at least 8 hours after taking a dose. The risk of CNS depression or impairment is increased by concurrent use of other CNS depressants, including alcoholic beverages. Patients treated with lasmiditan have been reported to have higher “drug-liking” scores than those receiving placebo, and the abuse potential of the new drug has been compared with that of alprazolam. The drug-liking scores were lower than those with alprazolam, and lasmiditan has been included in Schedule V under the provisions of the Controlled Substances Act. As with the triptans, lasmiditan may be infrequently associated with serotonin syndrome (e.g., mental status changes, incoordination, GI effects), and the risk of this response is increased by concurrent use of other serotonergic drugs (e.g., sertraline, venlafaxine, amitriptyline). There are no studies of lasmiditan in pregnant or lactating women, but animal studies suggest there is a risk of harm if the medication is used during pregnancy or lactation. Its effectiveness and safety in pediatric patients have not been established. Following oral administration, lasmiditan is rapidly absorbed. It undergoes hepatic and extrahepatic metabolism to inactive metabolites, primarily by non-CYP enzymes. Approximately two-thirds of a dose are eliminated as metabolites in the urine. Dosage adjustment is not necessary in patients with renal impairment or mild to moderate hepatic impairment. Lasmiditan has not been studied in patients with severe hepatic impairment, and its use in these patients is not recommended. When used concurrently with drugs that lower heart rate (e.g., propranolol), lasmiditan decreases heart rate by an additional 5 beats per minute, and treatment should be closely monitored in patients in whom a reduction in heart rate is a concern. Lasmiditan inhibits P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP), and its concomitant use with substrates of P-gp (e.g., dabigatran [Pradaxa–Boehringer Ingelheim]) or BCRP (e.g., rosuvastatin) should be avoided. The recommended dose of lasmiditan is 50 mg, 100 mg, or 200 mg with or without food, as needed. A second dose has not been shown to be effective for the same migraine attack, and no more than one dose should be taken in a 24-hour period. The safety of treating an average of more than four migraine attacks in a 30-day period has not been established. Lasmiditan hemisuccinate is supplied in film-coated tablets in amounts equivalent to 50 mg and 100 mg of lasmiditan. Tabled 1New therapeutic agents marketed in the United States in 2020: Part 1Generic nameTrade name (manufacturer)Therapeutic classificationRoute of administrationFDA classificationaFDA classification of new drugs: 1 = new molecular entity; P = priority review; S = standard review.Eptinezumab-jjmrVyepti (Lundbeck)Agent for migraineI.V.SbA biological approved through an FDA procedure that does not assign a numerical classification.Lasmiditan hemisuccinateReyvow (Lilly)Agent for migraineOral1-SLemborexantDayvigo (Eisai)HypnoticOral1-SRimegepant sulfateNurtec ODT (Biohaven)Agent for migraineOral1-PUbrogepantUbrelvy (Allergan)Agent for migraineOral1-Sa FDA classification of new drugs: 1 = new molecular entity; P = priority review; S = standard review.b A biological approved through an FDA procedure that does not assign a numerical classification. Open table in a new tab Comparison of lasmiditan with the triptans (oral sumatriptan is used for the comparisons) Advantages▪Has a more selective action and has not been associated with vasoconstrictive effects.▪Is safer for use in a broader range of patients, whereas sumatriptan is contraindicated in patients with peripheral vascular disease, ischemic bowel disease, uncontrolled hypertension, Wolff-Parkinson-White syndrome or a history of coronary artery disease/vasospasm, stroke, transient ischemic attack, or hemiplegic or basilar migraine; in patients with severe hepatic impairment; recent (within 24 hours) use of another triptan or ergotamine-containing medication; or concurrent or recent (past 2 weeks) use of an MOA inhibitor.▪Is less likely to cause chest, throat, neck, or jaw pain or pressure, or lower seizure threshold.▪Dosage adjustment is not necessary in patients with mild to moderate hepatic impairment. Disadvantages▪Has not been directly compared with triptans in clinical studies.▪Is more likely to cause a CNS depressant action and interact with other CNS depressants.▪Is a controlled substance (Schedule V; risk of problems is low).▪Is more likely to interact with heart rate–lowering drugs and P-gp and BCRP substrates.▪A second dose has not been shown to be effective for the same migraine attack.▪Formulations and routes of administration are more limited, whereas sumatriptan is also available in formulations for intranasal use and S.C. injection. ▪Has a more selective action and has not been associated with vasoconstrictive effects.▪Is safer for use in a broader range of patients, whereas sumatriptan is contraindicated in patients with peripheral vascular disease, ischemic bowel disease, uncontrolled hypertension, Wolff-Parkinson-White syndrome or a history of coronary artery disease/vasospasm, stroke, transient ischemic attack, or hemiplegic or basilar migraine; in patients with severe hepatic impairment; recent (within 24 hours) use of another triptan or ergotamine-containing medication; or concurrent or recent (past 2 weeks) use of an MOA inhibitor.▪Is less likely to cause chest, throat, neck, or jaw pain or pressure, or lower seizure threshold.▪Dosage adjustment is not necessary in patients with mild to moderate hepatic impairment. ▪Has not been directly compared with triptans in clinical studies.▪Is more likely to cause a CNS depressant action and interact with other CNS depressants.▪Is a controlled substance (Schedule V; risk of problems is low).▪Is more likely to interact with heart rate–lowering drugs and P-gp and BCRP substrates.▪A second dose has not been shown to be effective for the same migraine attack.▪Formulations and routes of administration are more limited, whereas sumatriptan is also available in formulations for intranasal use and S.C. injection. Calcitonin gene-related peptide (CGRP) is a neuropeptide that is distributed primarily in the central and peripheral nervous systems and acts as a vasodilator. It is involved in the transmission of pain impulses, and elevated concentrations have been associated with migraine attacks. In 2018, three monoclonal antibodies—erenumab (Aimovig–Amgen), fremanezumab (Ajovy–Teva Pharmaceuticals), and galcanezumab (Emgality–Eli Lilly)—were marketed as the first agents in a new class of CGRP antagonists. Each of these agents is administered subcutaneously for preventive treatment of migraine. Two new orally administered small-molecule CGRP receptor antagonists were marketed in early 2020 for acute but not preventive treatment of migraine, and they are considered individually in the following sections. Ubrogepant (Ubrelvy–Allergan) is indicated for acute treatment of migraine with or without aura in adults. It was evaluated in two placebo-controlled trials in which efficacy was established by an effect on pain freedom and MBS freedom at 2 hours. With a 100-mg dose of ubrogepant, 21% of patients were pain free at 2 hours, compared with 12% of those receiving placebo. Thirty-eight percent of patients treated with ubrogepant were MBS free at 2 hours, compared with 28% of those receiving placebo. There are no data to suggest that ubrogepant is more effective than the triptans or other previously marketed agents, but it may be effective in some patients who do not experience an adequate response with the other agents. In addition, its different mechanism of action and safety profile may be of value in patients who have factors that place them at risk of adverse events with other agents, or in whom other agents are not well tolerated. Ubrogepant is well tolerated, and the most commonly experienced adverse events include nausea (4%), somnolence (3%), and dry mouth (2%). Unlike the triptans, which are contraindicated in patients with several types of cardiovascular and other vascular diseases, ubrogepant has not been associated with these risks. There are no studies of ubrogepant in pregnant or lactating women, and the risk of harm appears to be low. Although animal studies suggest that some risk may exist, the potential problems identified occurred with doses or plasma exposures that are far higher than those experienced with the recommended dosage. Following oral administration, ubrogepant is rapidly absorbed. It is metabolized primarily via the CYP3A4 pathway and excreted mostly via the biliary/fecal route. Approximately 42% and 6% of a dose is recovered as unchanged drug in the feces and urine, respectively. Dosage adjustment is not necessary in patients with mild or moderate hepatic or mild or moderate renal impairment. A lower dosage is recommended in patients with severe hepatic or renal impairment, but use of ubrogepant in patients with end-stage renal disease should be avoided. Ubrogepant's activity is increased by CYP3A4 inhibitors, and concurrent use with strong inhibitors of this pathway (e.g., clarithromycin, itraconazole), is contraindicated. A lower dosage of ubrogepant should be used in patients also taking a moderate CYP3A4 inhibitor (e.g., cyclosporine, fluconazole, grapefruit products, verapamil) or weak CYP3A4 inhibitor. Conversely, the new drug's activity is decreased by strong CYP3A4 inducers (e.g., carbamazepine, phenytoin, rifampin, St. John's wort), and concurrent use should be avoided. Ubrogepant is a substrate of BCRP and P-gp efflux transporters. Its activity may be increased by concurrent use of BCRP and/or P-gp–only inhibitors (e.g., carvedilol, eltrombopag, quinidine, curcumin), and a lower dosage of ubrogepant is recommended. The recommended dosage of ubrogepant is 50 mg or 100 mg with or without food. If needed, a second dose may be administered at least 2 hours after the first dose, and the maximum dose in a 24-hour period is 200 mg. In patients being treated with a moderate CYP3A4 inhibitor, the recommended initial dose is 50 mg, but a second dose should not be administered within 24 hours. In patients being treated with a weak CYP3A4 inhibitor, a BCRP or a P-gp–only inhibitor, or in patients who have severe hepatic or renal impairment, the recommended initial dose is 50 mg. If needed, a second 50-mg dose may be taken at least 2 hours later. In patients being treated with a moderate or weak CYP3A4 inducer, the recommended initial dose is 100 mg, and if needed, a second dose of 100 mg may be taken at least 2 hours later. Ubrogepant tablets are supplied in 50- and 100-mg potencies. Comparison of ubrogepant with the triptans (oral sumatriptan is used for the comparisons) Advantages▪Is safer for use in a broader range of patients, whereas sumatriptan is contraindicated in patients with peripheral vascular disease, ischemic bowel disease, uncontrolled hypertension, Wolff-Parkinson-White syndrome or a history of coronary artery disease/vasospasm, stroke, transient ischemic attack, or hemiplegic or basilar migraine; in patients with severe hepatic impairment; recent (within 24 hours) use of another triptan or ergotamine-containing medication; or concurrent or recent (past 2 weeks) use of an MOA inhibitor.▪Is less likely to cause chest, throat, neck, or jaw pain or pressure, or lower seizure threshold. Disadvantages▪Has not been directly compared with triptans in clinical studies.▪May be less effective (based on data for individual agents in the absence of comparative studies).▪Concurrent use with strong CYP3A4 inhibitors is contraindicated, and concurrent use with strong CYP3A4 inducers should be avoided.▪Dosage adjustment is recommended in patients also taking moderate or weak CYP3A4 inhibitors and inducers or P-gp and/or BCRP inhibitors.▪Formulations and routes of administration are more limited, whereas sumatriptan is also available in formulations for intranasal use and S.C. injection. ▪Is safer for use in a broader range of patients, whereas sumatriptan is contraindicated in patients with peripheral vascular disease, ischemic bowel disease, uncontrolled hypertension, Wolff-Parkinson-White syndrome or a history of coronary artery disease/vasospasm, stroke, transient ischemic attack, or hemiplegic or basilar migraine; in patients with severe hepatic impairment; recent (within 24 hours) use of another triptan or ergotamine-containing medication; or concurrent or recent (past 2 weeks) use of an MOA inhibitor.▪Is less likely to cause chest, throat, neck, or jaw pain or pressure, or lower seizure threshold. ▪Has not been directly compared with triptans in clinical studies.▪May be less effective (based on data for individual agents in the absence of comparative studies).▪Concurrent use with strong CYP3A4 inhibitors is contraindicated, and concurrent use with strong CYP3A4 inducers should be avoided.▪Dosage adjustment is recommended in patients also taking moderate or weak CYP3A4 inhibitors and inducers or P-gp and/or BCRP inhibitors.▪Formulations and routes of administration are more limited, whereas sumatriptan is also available in formulations for intranasal use and S.C. injection. Rimegepant sulfate (Nurtec ODT–Biohaven) was the second orally administered CGRP receptor antagonist to be marketed in 2020. Like ubrogepant, it is indicated for acute treatment of migraine with or without aura in adults. It was evaluated in a placebo-controlled trial in which efficacy was established by an effect on pain freedom and MBS freedom at 2 hours. Twenty-one percent of patients treated with rimegepant were pain free at 2 hours, compared with 11% of those receiving placebo. Thirty-five percent of patients treated with rimegepant were MBS free at 2 hours, compared with 27% of those receiving placebo. Rimegepant has not been evaluated in studies designed to directly compare it with triptans or other agents used for acute treatment of migraine, but it may be effective in some patients who do not experience an adequate response with the other agents. Rimegepant is well tolerated, and the most commonly experienced adverse events include nausea (2%) and hypersensitivity reactions (less than 1%). Severe hypersensitivity reactions, including dyspnea and rash, can occur days after administration. There are no or limited data on use of rimegepant in pregnant or lactating women, but the risk of harm appears to be low. Although animal studies suggest that some risk may exist, the potential problems identified occurred with doses/plasma exposures that are far higher than those experienced with the recommended dosage. Accreditation information Provider: APhATarget audience: PharmacistsRelease date: February 1, 2021Expiration date: February 1, 2024Learning level: 1ACPE number: 0202-0000-21-124-H01-PCPE credit: 1 hour (0.1 CEUs)Fee: There is no fee associated with this activity for APhA members. There is a $25 fee for nonmembers.APhA is accredited by the Accreditation Council for Pharmacy Education (ACPE) as a provider of continuing pharmacy education (CPE). The ACPE Universal Activity Number assigned to this activity by the accredited provider is 0202-0000-21-124-H01-P.Advisory board: Mark S. Johnson, PharmD, BCPS, professor, Department of Pharmacy Practice, and director of postgraduate education, Bernard J. Dunn School of Pharmacy, Shenandoah University, Winchester, VA.Disclosures: Mark S. Johnson, PharmD, BCPS, declares that he and his spouse hold stock in Merck & Co. Daniel A. Hussar, PhD, FAPhA; Eric F. Hussar, MD; and APhA's editorial staff declare no conflicts of interest or financial interests in any product or service mentioned in this activity, including grants, employment, gifts, stock holdings, and honoraria. For complete staff disclosures, please see www.pharmacist.com/apha-disclosures.Development: This home-study CPE activity was developed by APhA. Provider: APhA Target audience: Pharmacists Release date: February 1, 2021 Expiration date: February 1, 2024 Learning level: 1 ACPE number: 0202-0000-21-124-H01-P CPE credit: 1 hour (0.1 CEUs) Fee: There is no fee associated with this activity for APhA members. There is a $25 fee for nonmembers. APhA is accredited by the Accreditation Council for Pharmacy Education (ACPE) as a provider of continuing pharmacy education (CPE). The ACPE Universal Activity Number assigned to this activity by the accredited provider is 0202-0000-21-124-H01-P. Advisory board: Mark S. Johnson, PharmD, BCPS, professor, Department of Pharmacy Practice, and director of postgraduate education, Bernard J. Dunn School of Pharmacy, Shenandoah University, Winchester, VA. Disclosures: Mark S. Johnson, PharmD, BCPS, declares that he and his spouse hold stock in Merck & Co. Daniel A. Hussar, PhD, FAPhA; Eric F. Hussar, MD; and APhA's editorial staff declare no conflicts of interest or financial interests in any product or service mentioned in this activity, including grants, employment, gifts, stock holdings, and honoraria. For complete staff disclosures, please see www.pharmacist.com/apha-disclosures. Development: This home-study CPE activity was developed by APhA. Following oral administration, rimegepant is rapidly absorbed, and its absolute oral bioavailability is approximately 64%. It is metabolized primarily via the CYP3A4 pathway and, to a lesser extent, via the CYP2C9 pathway. Most of a dose (78%) is recovered in the feces, and unchanged rimegepant is the major component in the feces (42%) and urine (51%). Dosage adjustment is not necessary in patients with mild or moderate hepatic impairment, but use of rimegepant should be avoided in patients with severe hepatic impairment because of its significantly higher plasma concentrations. No dosage adjustment is necessary in patients with mild, moderate, or severe renal impairment, but the new drug has not been studied in patients with end-stage renal disease or on dialysis, and its use should be avoided in these patients. Rimegepant's activity is increased by inhibitors of CYP3A4, BCRP, and P-gp. Concurrent use of rimegepant should be avoided in patients treated with these agents, and the dosage should be adjusted in patients being treated with a moderate CYP3A4 inhibitor. Rimegepant's activity may be decreased by strong or moderate inducers of CYP3A4, and concurrent use should be avoided. The recommended dosage of rimegepant is 75 mg. Because rimegepant has a longer duration of action than ubrogepant, the initial 75-mg dose is the maximum dose that should be used in a 24-hour period. In patients being treated with a moderate CYP3A4 inhibitor, another dose should be avoided within 48 hours. The safety of treating more than 15 migraines in a 30-day period has not been established. Rimegepant sulfate is supplied in an orally disintegrating tablet (ODT) formulation in an amount equivalent to 75 mg of rimegepant in blister packs of eight tablets. The foil covering of a blister pack should be peeled back to remove the tablet; the tablet should not be pushed through the foil. A tablet is placed on or under the tongue, allowed to disintegrate in the saliva, and swallowed. Comparison of rimegepant with ubrogepant Advantages▪Has a longer duration of action, and a second dose is not needed during each 24-hour treatment period.▪Is supplied in an ODT formulation that disintegrates in the saliva, and additional liquid is not needed. Disadvantages▪May be more likely to cause hypersensitivity reactions.▪Use should be avoided in patients being treated with a moderate CYP3A inducer or with P-gp or BCRP inhibitors, whereas ubrogepant in an adjusted dosage may be used concurrently.▪Use should be avoided in patients with severe hepatic impairment, whereas ubrogepant may be used in a reduced dosage. ▪Has a longer duration of action, and a second dose is not needed during each 24-hour treatment period.▪Is supplied in an ODT formulation that disintegrates in the saliva, and additional liquid is not needed. ▪May be more likely to cause hypersensitivity reactions.▪Use should be avoided in patients being treated with a moderate CYP3A inducer or with P-gp or BCRP inhibitors, whereas ubrogepant in an adjusted dosage may be used concurrently.▪Use should be avoided in patients with severe hepatic impairment, whereas ubrogepant may be used in a reduced dosage. Patients who experience 4 to 14 migraine days per month (i.e., monthly migraine days, or MMD) are classified as having episodic migraines, whereas those with 15 or more headache days per month with at least 8 MMD are classified as having chronic migraine. When migraine triggers cannot be identified or avoided, patients who experience frequent migraine attacks are often candidates for preventive management to reduce the frequency and severity of attacks. Certain beta-blockers (i.e., propranolol, timolol) and antiepileptic drugs (i.e., divalproex sodium, topiramate) have labeled indications for migraine prevention. However, these agents are of limited effectiveness in many patients and may be associated with unacceptable adverse events and other risks. The CGRP antagonists erenumab, fremanezumab, and galcanezumab— approved in 2018—provide additional options for prophylaxis in patients who experience frequent migraine attacks. Erenumab binds to the CGRP receptor and antagonizes CGRP receptor function, whereas fremanezumab and galcanezumab bind to the CGRP ligand and block its binding to the receptor. All three of these agents are administered subcutaneously for preventive treatment of migraine in adults, but they are not indicated for acute treatment of migraine. Galcanezumab has also been subsequently approved for treatment of patients who experience episodic cluster headache. Eptinezumab-jjmr (Vyepti–Lundbeck) is a CGRP antagonist that, like fremanezumab and galcanezumab, binds to CGRP ligand and blocks its binding to the receptor. It is the fourth monoclonal antibody CGRP antagonist to be approved for preventive treatment of migraine. Unlike the previous agents, which are administered subcutaneously, eptinezumab is administered intravenously. Eptinezumab was evaluated in two placebo-controlled trials, one in patients with episodic migraine and the other in patients with chronic migraine. Study endpoints were measured at 12 weeks. Patients with episodic migraine experienced, on average, reductions in MMD of 3.9 and 4.3 with dosages of 100 mg and 300 mg, respectively, compared with a reduction of 3.2 with placebo. Fifty percent and 56%
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Apr 1, 2024
Richard B Lipton 
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