Vyepti Drug Information
Generic name: EPTINEZUMAB-JJMR
Calcitonin Gene-related Peptide Antagonist [EPC]
Uses of Vyepti
is indicated for the preventive treatment of migraine in adults. VYEPTI is a calcitonin gene-related peptide antagonist indicated for the preventive treatment of migraine in adults
Dosage & Administration of Vyepti
Recommended Dosing
The recommended dosage is 100 mg administered by intravenous infusion every 3 months. Some patients may benefit from a dosage of 300 mg administered by intravenous infusion every 3 months.
Dilution Instructions
VYEPTI requires dilution prior to administration. Dilute only in 100 mL 0.9% Sodium Chloride Injection, USP. The infusion bags must be made of polyvinyl chloride (PVC), polyethylene (PE), or polyolefin (PO). Use appropriate aseptic technique when preparing VYEPTI solution for intravenous infusion. VYEPTI single-dose vials contain no preservative; discard unused portion remaining in the vial.
Dilution 100 mg dose: To prepare the solution, withdraw 1 mL of VYEPTI from a single-dose vial using a sterile needle and syringe. Inject the 1 mL content into a 100 mL bag of 0.9% Sodium Chloride Injection, USP. 300 mg dose: To prepare the solution, withdraw 1 mL of VYEPTI from each of 3 single-dose vials using a sterile needle and syringe. Inject the resulting 3 mL content into a 100 mL bag of 0.9% Sodium Chloride Injection, USP. Storage and Handling of Diluted Product Gently invert the VYEPTI solution to mix completely.
Do not shake. Following dilution, VYEPTI solution must be infused within 8 hours. During this time, VYEPTI solution should be stored at room temperature, 20°C to 25°C (68°F to 77°F). Do not freeze.
Infusion
Administration Instructions Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. Do not use if the liquid contains visible particulate matter or is cloudy or discolored . No other medications should be administered through the infusion set or mixed with VYEPTI. VYEPTI is for intravenous infusion only; infuse over approximately 30 minutes. Do not administer VYEPTI as an intravenous push or bolus injection.
Use an intravenous infusion set with a 0.2 micron or 0.22 micron in-line or add-on sterile filter. After the infusion is complete, flush the line with 20 mL of 0.9% Sodium Chloride Injection, USP.
Side Effects of Vyepti
Clinical Trials Experience
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice. The safety of VYEPTI was evaluated in 2076 patients with migraine who received at least one dose of VYEPTI, representing 1615 patient-years of exposure; of these, 1524 patients were exposed to 100 mg or 300 mg. Across all doses, 1872 patients were exposed for at least 6 months and 991 patients were exposed for 12 months.
In the placebo-controlled clinical studies (Study 1 and Study 2) of 1372 patients, 579 patients received at least one dose of VYEPTI 100 mg, 574 patients received at least one dose of VYEPTI 300 mg, and 588 patients received placebo . Approximately 86% were female, 89% were white, and the mean age was 40.4 years at study entry. The most common (incidence at least 2% and at least 2% greater than placebo) adverse reactions in the clinical trials for the preventive treatment of migraine were nasopharyngitis and hypersensitivity. Table 1 summarizes the adverse reactions that occurred during Study 1 and Study 2. Table 1. Adverse Reactions Occurring with an Incidence of at Least 2% for VYEPTI and at Least 2% Greater than Placebo in Studies 1 and 2 Adverse Reactions VYEPTI 100 mg N=579% VYEPTI 300 mg N=574% Placebo N=588% Nasopharyngitis 6 8 6 Hypersensitivity reactions* 1 2 0 * Hypersensitivity reactions includes multiple related adverse event terms, such as hypersensitivity, pruritus, and flushing/hot flush that occurred on the day of dosing.
In Study 1 and Study 2, 1.9% of patients treated with VYEPTI discontinued treatment because of adverse reactions . In study 3, the safety profile observed in 480 patients who were randomized and treated (238 to VYEPTI 100 mg and 242 to placebo) was consistent with the safety profile observed in the two pivotal placebo-controlled studies with VYEPTI (Study 1 and 2).
Postmarketing Experience
The following adverse reactions have been identified during postapproval use of VYEPTI. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. Immune System Disorders: Anaphylaxis General Disorders and Administration Site Conditions: Fatigue Vascular Disorders: Hypertension , Raynaud’s phenomenon
Warnings & Cautions for Vyepti
Hypersensitivity Reactions Hypersensitivity reactions, including angioedema, urticaria, facial flushing, dyspnea, and rash
have occurred with VYEPTI in clinical trials and in the postmarketing setting. Most hypersensitivity reactions occurred during infusion and were not serious, but often led to discontinuation or required treatment. Serious hypersensitivity reactions may occur.
Cases of anaphylaxis have been reported in the postmarketing setting. If a hypersensitivity reaction occurs, consider discontinuing VYEPTI and institute appropriate therapy .
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 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.
Pregnancy Safety for Vyepti
Pregnancy Pregnancy Exposure Registry There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to VYEPTI during pregnancy. Healthcare providers are encouraged to register pregnant patients, or pregnant women may enroll themselves in the registry by calling 1-855-810-8549 or by contacting the company at www.vyeptipregnancyregistry.lundbeck.com. Risk Summary There are no adequate data on developmental risks associated with the use of VYEPTI in pregnant women.
No adverse developmental effects were observed following administration of eptinezumab-jjmr to pregnant animals at doses greater than those used clinically . In the U.S. general population, the estimated background risk of major birth defects and miscarriages in clinically recognized pregnancies is 2%-4% and 15%-20%, respectively. The estimated rate of major birth defects (2.2%-2.9%) and miscarriage (17%) among deliveries to women with migraine are similar to rates reported in women without migraine. Clinical Considerations Disease-Associated Maternal and/or Embryo/Fetal Risk Published data have suggested that women with migraine may be at increased risk of preeclampsia and gestational hypertension during pregnancy.
Data Animal Data When eptinezumab-jjmr (0, 75, or 150 mg/kg) was administered weekly to female rats and rabbits by intravenous injection throughout organogenesis, no adverse effects on embryofetal development were observed. The higher dose tested (150 mg/kg) is 30 times the maximum recommended human dose (MRHD) of 300 mg, on a body weight basis (mg/kg). When eptinezumab-jjmr (0, 75, or 150 mg/kg) was administered weekly to female rats throughout pregnancy and lactation, no adverse effects on pre- and postnatal development were observed. The higher dose tested (150 mg/kg) is 30 times the MRHD, on a mg/kg basis.
Pediatric Use of Vyepti
Pediatric Use Safety and effectiveness in pediatric patients have not been established.
Contraindications for 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 . VYEPTI is contraindicated in patients with serious hypersensitivity to eptinezumab-jjmr or to any of the excipients
Clinical Studies of Vyepti
Difference from placebo -0.7 -1.1 p -value 0.018 <0.001 ≥50%
MMD responders – Months 1-3 % Responders 49.8% 56.3% 37.4% Difference from placebo 12.4% 18.9% p - value 0.009* <0.001 ≥75% MMD responders – Months 1-3 % Responders 22.2% 29.7% 16.2% Difference from placebo 6.0% 13.5% p -value NS** <0.001 * 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 1. Change from Baseline in Monthly Migraine Days in Study 1 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 2. Distribution of Change from Baseline in Mean Monthly Migraine Days over Months 1 to 3 by Treatment Group in Study 1 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. Figure 3. Percentage of Patients with a Migraine from Day -1 (Day Prior to Infusion) to Day 7 in Study 1 Study 2: Chronic Migraine 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. Table 3. Efficacy Endpoint Results in Study 2 VYEPTI100 mg N=356 VYEPTI300 mg N=350 Placebo N=366 Monthly Migraine Days (MMD) – Months 1-3 Change from baseline -7.7 -8.2 -
Difference from placebo -2.0 -2.6 p- value <0.001 <0.001 ≥50%
MMD responders –Months 1-3 % Responders 57.6% 61.4% 39.3% Difference from placebo 18.2% 22.1% p - value <0.001 <0.001 ≥75% MMD responders –Months 1-3 % Responders 26.7% 33.1% 15.0% Difference from placebo 11.7% 18.1% p -value <0.001 <0.001 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 4. Change from Baseline in Monthly Migraine Days in Study 2 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 5. Distribution of Change from Baseline in Mean Monthly Migraine Days over Months 1-3 by Treatment Group in Study 2 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. Figure 6. Percentage of Patients with a Migraine from Day -1 (Day Prior to Infusion) to Day 7 in Study 2 Study 3: Episodic Migraine or Chronic Migraine 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. Figure 1. Change from Baseline in Monthly Migraine Days in Study 1 Figure 2. Distribution of Change from Baseline in Mean Monthly Migraine Days over Months 1 to 3 by Treatment Group in Study 1 Figure 3. Percentage of Patients with a Migraine from Day -1 (Day Prior to Infusion) to Day 7 in Study 1 Figure 4. Change from Baseline in Monthly Migraine Days in Study 2 Figure 5. Distribution of Change from Baseline in Mean Monthly Migraine Days over Months 1-3 by Treatment Group in Study 2 Figure 6. Percentage of Patients with a Migraine from Day -1 (Day Prior to Infusion) to Day 7 in Study 2
Drug information sourced from the FDA. This content is for informational purposes only and does not constitute medical advice. Consult a healthcare professional before making any medication decisions.
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