Ajovy Drug Information
Generic name: FREMANEZUMAB-VFRM
Uses of Ajovy
AJOVY is indicated for: the preventive treatment of migraine in adults, and the preventive treatment of episodic migraine in pediatric patients who are 6 to 17 years of age and who weigh 45 kg or more.
Dosage & Administration of Ajovy
Recommended Dosage Adults
The recommended dosage in adults for the preventive treatment of migraine is administered by subcutaneous injection as one of the following options: 225 mg monthly, or 675 mg every 3 months (quarterly), which is administered as three consecutive subcutaneous injections of 225 mg each. When switching dosage options, administer the first dose of the new regimen on the next scheduled date of administration. AJOVY is not approved in pediatric patients weighing less than 45 kg because of the lack of an appropriate strength presentation.
Missed Dose If a dose of AJOVY is missed, administer as soon as possible. Thereafter, AJOVY can be scheduled from the date of the last dose.
Important Administration Instructions AJOVY is for subcutaneous use only. AJOVY may be administered by healthcare providers, patients 13 years of age and older, and/or caregivers. In pediatric patients 6 to 12 years of age, AJOVY must be administered by a healthcare provider or adult caregiver.
Prior to use, provide proper training to patients and/or caregivers on the preparation and administration of AJOVY prefilled syringe, including aseptic technique: Remove AJOVY from the refrigerator. Prior to use, allow AJOVY to sit at room temperature for 30 minutes protected from direct sunlight. Do not warm by using a heat source such as hot water or a microwave.
Do not use AJOVY if it has been at room temperature for 7 days or longer. Follow aseptic injection technique every time AJOVY is administered. Inspect AJOVY for particles or discoloration prior to administration.
Do not use if the solution is cloudy, discolored, or contains particles. Administer AJOVY by subcutaneous injection into areas of the abdomen, thigh, or upper arm that are not tender, bruised, red, or indurated. For multiple injections, you may use the same body site, but not the exact location of the previous injection.
Do not co-administer AJOVY with other injectable drugs at the same injection site.
Side Effects of Ajovy
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. Adults The safety of AJOVY was evaluated in 2512 patients with migraine who received at least 1 dose of AJOVY, representing 1279 patient-years of exposure. In the controlled trials, 87% of patients were female, 80% were White, and the mean age was 41 years.
The most common adverse reactions in the clinical trials for the preventive treatment of migraine (incidence at least 5% and greater than placebo) were injection site reactions. The adverse reactions that most commonly led to discontinuations were injection site reactions (1%). Table 1 summarizes adverse reactions reported in the 3-month placebo-controlled studies (Study 1 and Study 2), and the 1-month follow-up period after those studies.
Table 1: Adverse Reactions Occurring with an Incidence of At Least 2% for Either Dosing Regimen of AJOVY and At Least 2% Greater Than Placebo in Studies 1 and 2 a Injection site reactions include multiple related adverse event terms, such as injection site pain, induration, and erythema. In the placebo-controlled trial (Study 3), 123 pediatric patients with episodic migraine were treated with AJOVY. The most common adverse reactions of AJOVY observed in Study 3 were injection site reactions.
Hypersensitivity reactions were also observed. Overall, the safety profile in pediatric patients is similar to the known safety profile in adults.
Postmarketing Experience
The following adverse reactions have been identified during postapproval use of AJOVY. 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. Gastrointestinal Disorders: Constipation Immune System Disorders: Anaphylactic reactions and angioedema Vascular Disorders: Hypertension, Raynaud’s phenomenon
| Adverse Reaction | AJOVY 225 mg Monthly (n=290) % | AJOVY 675 mg Quarterly (n=667) % | Placebo Monthly (n=668) % |
|---|---|---|---|
| Injection site reactions a | 43 | 45 | 38 |
Warnings & Cautions for Ajovy
Hypersensitivity Reactions
Hypersensitivity reactions, including rash, pruritus, drug hypersensitivity, and urticaria, were reported with AJOVY in clinical trials. Most reactions were mild to moderate, but some led to discontinuation or required corticosteroid treatment. Most reactions were reported from within hours to one month after administration.
Cases of anaphylaxis and angioedema have been reported in the postmarketing setting. If a hypersensitivity reaction occurs, consider discontinuing AJOVY, and institute appropriate therapy.
Constipation with Serious Complications Constipation with serious complications has been reported following the use of monoclonal antibody CGRP antagonists, including AJOVY, in the postmarketing setting. There were cases with monoclonal antibody CGRP antagonists that required hospitalization, including cases where surgery was necessary. In a majority of these cases, the onset of constipation was reported after the first dose; however, patients have also presented with constipation later in treatment.
The monoclonal antibody CGRP antagonist was discontinued in many of the reported cases of constipation with serious complications. Monitor patients treated with AJOVY for severe constipation and manage as clinically appropriate. The concurrent use of medications that reduce gastrointestinal motility may increase the risk for more severe constipation and the potential for constipation-related complications.
Hypertension Development of hypertension and worsening of pre-existing hypertension have been reported following the use of CGRP antagonists, including AJOVY, 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. AJOVY was discontinued in many of the reported cases. Monitor patients treated with AJOVY for new-onset hypertension or worsening of pre-existing hypertension, and consider whether discontinuation of AJOVY is warranted if evaluation fails to establish an alternative etiology or blood pressure is inadequately controlled.
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.
AJOVY 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 Ajovy
Pregnancy Pregnancy Exposure Registry There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to AJOVY during pregnancy. Healthcare providers are encouraged to register pregnant patients, or pregnant women may enroll themselves in the registry by calling 1-833-927-2605 or visiting www.tevamigrainepregnancyregistry.com. Risk Summary There are no adequate data on the developmental risk associated with the use of AJOVY in pregnant women.
AJOVY has a long half-life. This should be taken into consideration for women who are pregnant or plan to become pregnant while using AJOVY. Administration of fremanezumab-vfrm to rats and rabbits during the period of organogenesis or to rats throughout pregnancy and lactation at doses resulting in plasma levels greater than those expected clinically did not result in adverse effects on development.
In the U.S. general population, the estimated background risk of major birth defects and miscarriage 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 fremanezumab-vfrm mg/kg was administered to male and female rats by weekly subcutaneous injection prior to and during mating and continuing in females throughout organogenesis, no adverse embryofetal effects were observed. The highest dose tested was associated with plasma exposures (AUC) approximately 2 times that in humans at a dose of 675 mg. Administration of fremanezumab-vfrm mg/kg weekly by subcutaneous injection to pregnant rabbits throughout the period of organogenesis produced no adverse effects on embryofetal development.
Administration of fremanezumab-vfrm mg/kg weekly by subcutaneous injection to female rats throughout pregnancy and lactation resulted in no adverse effects on pre- and postnatal development.
Pediatric Use of Ajovy
Pediatric Use Episodic Migraine The safety and effectiveness of AJOVY have been established in an adequate and well-controlled study for the preventive treatment of episodic migraine in pediatric patients who are 6 to 17 years of age and who weigh 45 kg or more (Study 3). The safety and efficacy profile of AJOVY in these patients was similar to the safety and efficacy profile seen in clinical trials in adults with migraine. AJOVY is not approved in pediatric patients weighing less than 45 kg because of the lack of an appropriate strength presentation.
The safety and effectiveness of AJOVY for the preventive treatment of episodic migraine in pediatric patients younger than 6 years of age have not been established. Juvenile Animal Toxicity Data Subcutaneous administration of fremanezumab-vfrm mg/kg to juvenile rats once weekly from postnatal day (PND) 28 to PND 63 resulted in no adverse effects on growth, sexual maturation, or neurobehavioral or reproductive function. The highest dose tested was associated with plasma drug exposures (AUC) approximately 58 times that in pediatric patients at the recommended human dose (225 mg), when calculated on a monthly basis.
Contraindications for Ajovy
AJOVY is contraindicated in patients with serious hypersensitivity to fremanezumab-vfrm or to any of the excipients. Reactions have included anaphylaxis and angioedema.
Clinical Studies of Ajovy
Adults The efficacy of AJOVY was evaluated as a preventive treatment of episodic or chronic migraine in adult patients in two multicenter, randomized, 3-month, double-blind, placebo-controlled studies (Study 1 and Study 2, respectively). Episodic Migraine Study 1 (NCT 02629861) included adults with a history of episodic migraine (patients with <15 headache days per month). All patients were randomized (1:1:1) to receive subcutaneous injections of either AJOVY 675 mg every three months (quarterly), AJOVY 225 mg monthly, or placebo monthly, over a 3-month treatment period.
Patients were allowed to use acute headache treatments during the study. A subset of patients (21%) was allowed to use one additional concomitant preventive medication. The study excluded patients with a history of significant cardiovascular disease, vascular ischemia, or thrombotic events, such as cerebrovascular accident, transient ischemic attacks, deep vein thrombosis, or pulmonary embolism.
The primary efficacy endpoint was the mean change from baseline in the monthly average number of migraine days during the 3-month treatment period. Secondary endpoints included the proportion of patients reaching at least a 50% reduction in monthly average number of migraine days during the 3-month treatment period, the mean change from baseline in the monthly average number of days of use of any acute headache medication during the 3-month treatment period, and the mean change from baseline in the number of migraine days during the first month of the treatment period. A total of 791 patients completed the 3-month double-blind phase.
The mean migraine frequency at baseline was approximately 9 migraine days per month, and was similar across treatment groups. Both monthly and quarterly dosing regimens of AJOVY demonstrated statistically significant improvements for efficacy endpoints compared to placebo over the 3-month period, as summarized in Table 3. A treatment benefit over placebo for both doses of AJOVY is seen across a range of changes from baseline in monthly migraine days.
Both monthly and quarterly dosing regimens of AJOVY treatment demonstrated statistically significant improvement for key efficacy outcomes compared to placebo, as summarized in Table 4. Figure 3 displays the mean change from baseline in the average monthly number of headache days of at least moderate severity in Study 2. Figure 3: Change from Baseline in Monthly Headache Days of At Least Moderate Severity in Study 2 a Figure 4 shows the distribution of change from baseline in monthly headache days of at least moderate severity at month 3 in bins of 3 days by treatment group.
A treatment benefit over placebo for both dosing regimens of AJOVY is seen across a range of changes from baseline in headache days. A subset of patients (21%) was allowed to use up to two additional concomitant preventive medications. The study excluded patients with clinically significant cardiovascular disease.
A total of 225 patients completed the 3-month, double-blind treatment period. Table 5: Efficacy Endpoints in Study 3 a One patient in the placebo group was excluded from the analysis due to not having at least 10 days of post-baseline efficacy data. Figure 5 displays the mean change from baseline in the average monthly number of migraine days in Study 3.
Figure 5: Distribution of Change from Baseline in Mean Monthly Migraine Days by Placebo and Combined AJOVY Group (Full Analysis Set) in Study 3.
| Study 1 Efficacy Endpoint | AJOVY 225 mg Monthly (N=287) | AJOVY 675 mg Quarterly (N=288) | Placebo (N=290) |
|---|---|---|---|
| Monthly migraine days (MMD) | |||
| Baseline migraine days | 8.9 | 9.2 | 9.1 |
| Change from baseline | -3.7 | -3.4 | -2.2 |
| Difference from placebo | -1.5 | -1.2 | |
| p-value | <0.001 | <0.001 | |
| ≥50% MMD responders | |||
| % responders | 47.7% | 44.4% | 27.9% |
| Difference from placebo | 19.8% | 16.5% | |
| p-value | <0.001 | <0.001 | |
| Monthly acute headache medication days | |||
| Change from baseline | -3.0 | -2.9 | -1.6 |
| Difference from placebo | -1.4 | -1.3 | |
| p-value | <0.001 | <0.001 | |
| Study 2 Efficacy Endpoint | AJOVY 225 mg a Monthly (N=375) | AJOVY 675 mg Quarterly (N=375) | Placebo (N=371) |
|---|---|---|---|
| Baseline headache days of any severity b | 20.3 | 20.4 | 20.3 |
| Baseline headache days of at least moderate severity c | 12.8 | 13.2 | 13.3 |
| Change from baseline in the monthly average number of headache days of at least moderate severity | -4.6 | -4.3 | -2.5 |
| Difference from placebo | -2.1 | -1.8 | |
| p-value | <0.001 | <0.001 | |
| Change from baseline in the monthly average number of migraine days in patients | -5.0 | -4.9 | -3.2 |
| Change from baseline in monthly average number of headache days of at least moderate severity at 4 weeks after 1 st dose | -4.6 | -4.6 | -2.3 |
| Percentage of patients with ≥ 50% reduction in monthly average number of headache days of at least moderate severity | 40.8% | 37.6% | 18.1% |
| Change from baseline in monthly average number of days of acute headache medication | -4.2 | -3.7 | -1.9 |
| Study 3 Efficacy Endpoint | AJOVY (N=123) | Placebo (N=111 a ) |
|---|---|---|
| Monthly migraine days (MMD) | ||
| Baseline migraine days | 7.8 | 7.5 |
| Change from baseline | -2.5 | -1.4 |
| Difference from placebo | -1.0 | |
| p-value | 0.021 | |
| ≥50% MMD responders | ||
| % responders | 47.2% | 27.0% |
| Difference from placebo | 20.2% | |
| p-value | 0.002 | |
| Monthly acute headache medication days | ||
| Change from baseline | -2.1 | -1.0 |
| Difference from placebo | -1.1 | |
| p-value | 0.002 | |
| Monthly headache days of at least moderate severity | ||
| Change from baseline | -2.6 | -1.5 |
| Difference from placebo | -1.1 | |
| p-value | 0.017 | |
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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