Get your patient on Vyepti (Eptinezumab-Jjmr)

VYEPTI is indicated for the preventive treatment of migraine in adults.

VYEPTI is a clear to slightly opalescent, colorless to brownish-yellow solution available as follows:

• Injection: 100 mg/mL in a single-dose vial

VYEPTI is contraindicated in patients with serious hypersensitivity to eptinezumab-jjmr or to any of the excipients in VYEPTI. Reactions have included anaphylaxis and angioedema

The following clinically significant adverse reactions are described elsewhere in the labeling:

• Hypersensitivity Reactions
  [see Warnings and Precautions (5.1)]
  .
• Hypertension
  [see

  5.2  Hypertension

  Development of hypertension and worsening of pre-existing hypertension have been reported following the use of CGRP antagonists, including VYEPTI, in the postmarketing setting. Some of the patients who developed new-onset hypertension had risk factors for hypertension. There were cases requiring initiation of pharmacological treatment for hypertension, and in some cases hospitalization. Hypertension may occur at any time during treatment, but was most frequently reported within 7 days of therapy initiation. The CGRP antagonist was discontinued in many of the reported cases.

  Monitor patients treated with VYEPTI for new-onset hypertension or worsening of pre-existing hypertension, and consider whether discontinuation of VYEPTI is warranted if evaluation fails to establish an alternative etiology or blood pressure is inadequately controlled.

  ]
• Raynaud’s Phenomenon
  [see

  5.3 Raynaud’s Phenomenon

  Development of Raynaud’s phenomenon and recurrence or worsening of pre-existing Raynaud’s phenomenon have been reported in the postmarketing setting following the use of CGRP antagonists. In reported cases with monoclonal antibody CGRP antagonists, symptom onset occurred a median of 71 days following dosing. Many of the cases reported serious outcomes, including hospitalizations and disability, generally related to debilitating pain. In most reported cases, discontinuation of the CGRP antagonist resulted in resolution of symptoms.

  VYEPTI should be discontinued if signs or symptoms of Raynaud’s phenomenon develop, and patients should be evaluated by a healthcare provider if symptoms do not resolve. Patients with a history of Raynaud’s phenomenon should be monitored for, and informed about the possibility of, worsening or recurrence of signs and symptoms.

  ]

Eptinezumab-jjmr is a humanized immunoglobulin G1 (IgG1) monoclonal antibody specific for calcitonin gene-related peptide (CGRP) ligand. Eptinezumab-jjmr has an approximate molecular weight of 143 kD. Eptinezumab-jjmr is produced in

VYEPTI (eptinezumab-jjmr) injection is a sterile, preservative-free, clear to slightly opalescent, colorless to brownish-yellow solution, for intravenous infusion. VYEPTI is supplied as a 100 mg/mL single-dose vial. Each mL contains 100 mg eptinezumab-jjmr formulated in L-histidine (1 mg), L-histidine hydrochloride monohydrate (2.8 mg), polysorbate 80 (0.15 mg), sorbitol (40.5 mg), and Water for Injection, USP, at a pH of 5.8.

Eptinezumab-jjmr is a humanized monoclonal antibody that binds to calcitonin gene-related peptide (CGRP) ligand and blocks its binding to the receptor.

The carcinogenic potential of eptinezumab-jjmr has not been assessed.

Genetic toxicology studies of eptinezumab-jjmr have not been conducted.

When eptinezumab-jjmr (0, 75, or 150 mg/kg) was administered weekly by intravenous injection to male and female rats prior to and during mating and continuing in females to gestation day 3-4, no adverse effects on fertility were observed. The higher dose tested (150 mg/kg) is 30 times the maximum recommended human dose of 300 mg, on a body weight basis (mg/kg).

The efficacy of VYEPTI was evaluated in three randomized, multicenter, placebo-controlled double-blind studies that enrolled patients with episodic and chronic migraine who were eligible for preventive treatment of migraine. In Study 1, which included patients with episodic migraine, and Study 2, which included  patients with chronic migraine,  either 100 mg or 300 mg VYEPTI was administered by intravenous infusion every 3 months. In Study 3, 100 mg VYEPTI was administered as a single intravenous infusion to patients with episodic or chronic migraine who were eligible for preventive migraine treatment and who had a concurrent migraine.  

Study 1 (NCT02559895) included adults with a history of episodic migraine (4 to 14 headache days per month, of which at least 4 were migraine days). A total of 665 patients were randomized to receive placebo (N=222), 100 mg VYEPTI (N=221), or 300 mg VYEPTI (N=222) every 3 months for 12 months. Patients were allowed to use concurrent acute migraine or headache medications, including migraine-specific medications (i.e., triptans, ergotamine derivatives), during the trial.

The study excluded patients with a history of cardiovascular disease (hypertension, ischemic heart disease), neurological disease, or cerebrovascular disease.

The primary efficacy endpoint was the change from baseline in mean monthly migraine days over Months 1-3. Secondary endpoints included the percentages of patients with 50% or greater, and 75% or greater reductions from baseline in monthly migraine days over Months 1-3.

Patients had a median age of 39 years (range: 18 to 71 years), 84% were female, and 84% were white. The mean migraine frequency at baseline was approximately 8.6 migraine days per month and was similar across treatment groups.

VYEPTI treatment demonstrated statistically significant improvements compared to placebo for the primary efficacy endpoint, as shown in Table 2; secondary endpoints are also summarized in Table 2.

              * Nominal statistical significance

              ** NS = Not statistically significant

Figure 1 shows the mean change from baseline in average monthly migraine days in Study 1. Patients treated with VYEPTI at both doses had greater mean decreases from baseline in mean monthly migraine days over Months 1-3 compared to placebo-treated patients.

Figure 2 shows the distribution of change from baseline in mean monthly migraine days through Month 3 by treatment group in 2-day increments.

Figure 3 demonstrates that greater percentages of placebo-treated patients had migraines on most days during the first 7 days of treatment compared to VYEPTI-treated patients in Study 1.

Study 2 (NCT02974153) included adults with a history of chronic migraine (15 to 26 headache days per month, of which at least 8 were migraine days). A total of 1072 patients were randomized and received placebo (N=366), 100 mg VYEPTI (N=356), or 300 mg VYEPTI (N=350) every 3 months for 6 months. Patients were allowed to use and to continue an established stable regimen of acute migraine or headache preventive medication (except onabotulinumtoxinA). Patients with a dual diagnosis of chronic migraine and medication overuse headache attributable to acute medication overuse (triptans, ergotamine, or combination analgesics greater than 10 days per month) were included in the study population. Patients using opioids or butalbital-containing products greater than 4 days per month were not allowed.

The study excluded patients with a history of cardiovascular disease (hypertension, ischemic heart disease), neurological disease, or cerebrovascular disease.

The primary efficacy endpoint was the change from baseline in mean monthly migraine days over Months 1-3. Secondary endpoints included the percentages of patients with 50% or greater and 75% or greater reductions from baseline in monthly migraine days over Months 1-3.

Patients had a median age of 41 years (range: 18 to 65 years), 88% were female, and 91% were white. Forty-one percent of patients were taking concomitant preventive medication for migraine. The mean migraine frequency at baseline was approximately 16.1 migraine days per month and was similar across treatment groups.

VYEPTI treatment demonstrated statistically significant improvements compared to placebo for the primary efficacy endpoint, as shown in Table 3; secondary endpoints are also summarized in Table 3.

Figure 4 shows the mean change from baseline in average monthly migraine days for Study 2. Patients treated with VYEPTI at both doses had greater mean decreases from baseline in mean monthly migraine days over Month 1-3 compared to placebo-treated patients.

Figure 5 shows the distribution of change from baseline in mean monthly migraine days through Month 3 by treatment group in 3-day increments.

Figure 6 demonstrates that greater percentages of placebo-treated patients had migraines on individual days during the first 7 days of treatment compared to VYEPTI-treated patients in Study 2.

Study 3 (NCT01719055) included adults who were candidates for preventive migraine therapy with VYEPTI and presented with a concurrent moderate to severe migraine on the day of infusion. A total of 480 patients were randomized to receive 100 mg VYEPTI (n=238) or placebo (n=242) as a single dose. VYEPTI demonstrated statistically significant improvements in headache pain freedom at 2 hours (VYEPTI 23.5% vs placebo 12%; p<0.001) and absence of most bothersome symptom (such as nausea, photophobia, or phonophobia) at 2 hours (VYEPTI 55.5% vs placebo 35.8%; p< 0.001) as compared to placebo. The dose of 300 mg VYEPTI was not evaluated in Study 3.

Eptinezumab-jjmr is a humanized monoclonal antibody that binds to calcitonin gene-related peptide (CGRP) ligand and blocks its binding to the receptor.