Efficacy for AJOVY

More migraine-free days with as few as 4 injection days a year and results seen as early as one week1,2

An expert’s review of the clinical profile

Dr Peter McAllister discusses the study designs, efficacy results, safety profile, and the dosing and administration information for AJOVY.
Show transcript

Hello and thank you for joining us for this informative video presentation on AJOVY—the long-acting anti-CGRP injection with the option of dosing only 4 times per year.

My name is Dr Peter McAllister from the New England Institute for Neurology and Headache where I’ve been Medical Director.

Today, we will discuss the clinical outcomes of the pivotal phase 3 and long-term extension trials of AJOVY—indicated for the preventive treatment of migraine in adults.

As we go through the data, think of the patients you may have, from those newly diagnosed, those on acute medications who may need preventive treatment, to patients who experience breakthrough headaches toward the end of their treatment’s dosing cycle. We hope the information here helps you make more informed treatment decisions for your patients.

Here is an overview of what we’ll cover today: We’ll start with the study designs of the pivotal phase 3 and long-term extension trials, review the efficacy results, the safety profile, and conclude with dosing and administration information.

Before we begin, please note: AJOVY is contraindicated in patients with serious hypersensitivity to fremanezumab-vfrm or to any of the excipients. Reactions have included anaphylaxis and angioedema.

So—let’s get started, shall we?

Let’s take a look at how the pivotal phase 3 and long-term extension trials for AJOVY were designed to ensure the integrity and rigor of the data, so that you know what may be expected from AJOVY.

AJOVY is an anti-calcitonin gene-related peptide, or anti-CGRP treatment. Its pivotal trials—known as HALO—consisted of two phase 3, 12-week, randomized, double-blind, placebo-controlled trials. One studied patients with chronic migraine, whereas the other studied patients with episodic migraine.

There were a total of 1,130 patients with chronic migraine and 875 patients with episodic migraine in the two studies.

Patients were randomized in a 1:1:1 ratio to one of three treatment arms. Either AJOVY Quarterly dosing, AJOVY Monthly dosing, or the placebo arm.

Once randomized, patients underwent a screening visit, a 28-day preintervention, run-in period, followed by a 12-week intervention period, with a final evaluation at Week 12.

Some of the patients in the 12-week HALO studies rolled over into the long-term extension study—a 12-month, multicenter, randomized, double-blind, parallel-group clinical trial.

Patients remained on the same 1:1 randomized dosing regimen of either quarterly or monthly dosing for duration of the 12 months. Please note that the long-term extension study was not placebo controlled, but patients were blinded as to the dosing regimen.

Keep in mind that 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.

We value your time and want to make sure you get the information that’s most relevant to you and your practice from this video presentation. Please choose which data you would like to see next. Later on, you will have the opportunity to see the other data if you’d like.

CHRONIC MIGRAINE

Let’s dive into the chronic migraine data from the phase 3 trials. As we do so, I would like for you to think about your patients who suffer from Chronic Migraine and how AJOVY may help.

The primary endpoint in the HALO chronic migraine trial, or HALO CM for short, was the mean change from the baseline in the monthly number of headache days of at least moderate severity for both quarterly and monthly dosing options.

As we can see, AJOVY quarterly dosing demonstrated a statistically significant improvement, with results seen as early as week 1. After 3 months there was a reduction of 4.7 headache days versus 3.3 days for placebo.

In the long-term extension study, the mean reduction from baseline was 6.4 headache days with quarterly dosing.

You should also know that in the HALO chronic migraine trial, similar results were demonstrated with monthly dosing.

It is important to note that the most common adverse reactions in clinical trials, at least 5% and greater than placebo, were injection site reactions.

Now that we’ve covered the primary endpoint results, let’s take it a step further and show published data that explored migraine days for selected dosing periods from the long-term extension study.

To assess AJOVY over these selected dosing periods, data for patients from the HALO trials who rolled over into the long-term extension study were included in the post hoc analyses. For now, let’s focus on patients with chronic migraine.

The chronic migraine data you’ll see here for quarterly dosing will show the mean number of weekly migraine days over two quarters. Within each quarter, weeks 1 through 2—the beginning of the dosing period—were compared to weeks 11 through 12—the end of the dosing period. Patients had an average baseline of 4 weekly migraine days.

In the first quarter, during the initial period of weeks 1 through 2, the mean number of weekly migraine days was 2.76.

Toward the end of the dosing period, you can see that the number was comparable.

Now let’s take a look at the second quarter. In the beginning of the next dose, for weeks 1 through 2, the mean number of weekly migraine days was 2.48, with that number staying about the same toward the end of the dosing period. Note that for all post hoc analyses, no determination of statistical significance can be made and no conclusions should be drawn.

Looking at everything together, the mean number of weekly migraine days for patients with chronic migraine on AJOVY were similar during weeks 1 through 2 versus 11 through 12.

With this in mind, how does this information compare to what you’re seeing in your clinical experience? It’s something worth thinking about.

The analyses also looked at the mean number of weekly migraine days for months 3, 6, 9, and 15 with monthly dosing. For weeks 1 through 3, or the beginning of the dosing period, these were the numbers. For weeks 4, we see that the number of migraine days was very similar. Therefore, as the chart indicates, the weekly number of migraine days was similar during weeks 1 through 3 versus week 4, for months 3, 6, 9, and 15. Note, for all post hoc analyses, no determination of statistical significance can be made and no conclusions should be drawn.

And now for another important efficacy measure studied in HALO as a secondary endpoint, referred to as “responder rates.” In HALO chronic migraine, the study measured the proportion of patients who experienced at least a 50% reduction in their headache days throughout the study period.

Looking at the numbers, you can see that a significant percentage of patients saw a reduction of at least 50% in their headache days as compared to the placebo group.

Furthermore, exploratory analyses showed 75 and 100% reductions for some patients. In your experience, how often do patients with chronic migraine typically cut their headache days by half or more?

With AJOVY, you can give your patients the chance to be migraine-free.

EPISODIC MIGRAINE

Let’s now proceed to the episodic migraine data from the phase 3 trials. The primary endpoint was the mean change from baseline in the monthly average number of migraine days for both quarterly and monthly dosing.

Taking a look at the data, patients experienced a statistically significant reduction of 4.2 migraine days 3 months after a quarterly dose of AJOVY versus 3.1 days with placebo, with some seeing results as early as one week.

Going into the long-term extension study, the mean change from baseline was 5.2 migraine days.

It’s important to mention that in the episodic migraine trial, similar results were demonstrated in the monthly dosing option as in the quarterly dosing just presented. From your clinical experience, how often do patients experience reductions of this kind? What could these reduction numbers mean for some of your patients?

Moving on, the most common adverse reactions in clinical trials at least 5% and greater than placebo were injection site reactions.

Having covered the primary endpoint results, let’s review the post hoc analyses of migraine days for selected dosing periods from the long-term extension study.

To assess AJOVY over these selected dosing periods, data for patients from the HALO trials who rolled over into the long-term extension study were included in the post hoc analyses. Let’s focus in now on the data as they relate to patients with episodic migraine.

The episodic migraine data you’ll see here for quarterly dosing will show the mean number of weekly migraine days over two quarters. Within each quarter, weeks 1 through 2—the beginning of the dosing period—were compared to weeks 11 through 12—the end of the dosing period. Patients had an average baseline of 2.3 weekly migraine days.

In the first quarter during weeks 1 through 2, the mean weekly number of migraine days was 1.45. Then toward the end of that dosing period this was the number—very similar to the beginning.

In the second quarter, the mean number of migraine days was 1.17 for weeks 1 through 2, and as that dosing period drew to a close at the 11 through 12 weeks mark, once again, that number was also similar. Note that for all post hoc analyses, no statistical determination of significance can be made and no conclusions should be drawn.

As we saw, the mean number of weekly migraine days for patients with episodic migraine on AJOVY were similar throughout the first and second quarters.

Thinking about your patients with episodic migraine, what comes to mind when you see these data?

Moving along, the study further looked at the mean number of weekly migraine days for months 3, 6, 9, and 15. For each of these months, weeks 1 through 3 were compared to week 4.

As can be seen in this chart, the number of migraine days was similar throughout the first 3 weeks versus week 4, and that was true for each of the months shown here. Note, for all post hoc analyses, no determination of statistical significance can be made and no conclusions should be drawn.

Responder rates were a secondary endpoint of the HALO episodic migraine trial. We see that over a third of patients saw a reduction of 50% or more in the number of migraine days with quarterly dosing versus placebo. Reductions for monthly dosing were similar and exploratory data for 75 and 100% reductions were also reported for HALO EM.

Looking at these responder rates, the question arises: What could these results mean for your patients who suffer from episodic migraine?

You can even give your patients a chance to be migraine-free with AJOVY.

AJOVY is contraindicated in patients with serious hypersensitivity to fremanezumab-vfrm or to any of the excipients. Reactions have included anaphylaxis and angioedema.

We know having all the information is important when making treatment decisions, so please select the data you’d like to see next.

Alongside efficacy, we know that the safety of your patients is a top priority. In this section, we will review the safety profile of AJOVY established in the clinical trials to help you make the most informed treatment decisions possible.

Here you can see adverse reactions reported by at least 2% of patients on AJOVY and greater than placebo from the HALO Chronic and Episodic Migraine trials.

Note that in HALO chronic and episodic migraine, less than 1% of patients experienced constipation, and less than 1% of patients experienced hypertension compared to less than 1% for placebo.

Additionally, less than or equal to 2% of patients discontinued due to adverse events in both the AJOVY and placebo treatment arms, and less than 1% of patients developed antibodies in either phase 3 trial for AJOVY.

Moving over to the long-term extension study, you can see the adverse reactions that occurred in more than 6% of patients.

Something else worth keeping in mind is that in the long-term extension study, 6% of patients discontinued due to lack of efficacy or adverse events, with the discontinuation rates comparable for quarterly and monthly dosing at 7% and 5%, respectively.

With that, we’ve reviewed study designs, the efficacy results, and the safety profile for AJOVY. Now that you’re familiar with these clinical outcomes, I’d like to emphasize that AJOVY is available in an autoinjector, with many features that your patients may find helpful, like a button-free, push-down mechanism, which locks out after use. It’s not made of natural rubber latex. What’s more, 97% of HCP and patient evaluators found that AJOVY Autoinjector easy to use in two Human Factor studies, so your patients can expect to handle their administrations with ease.

AJOVY can also be administered quarterly or monthly. For the quarterly dosing option, AJOVY is available in a Triple Pack, which contains 3 autoinjectors in one box.

For AJOVY, there’s no loading dose, no dose titration, and it can be administered at home or in-office.

And that concludes our clinical tour with AJOVY. We hope this video helps you in making informed treatment decisions for your migraine patients. We understand the challenges of living with migraine, and so we hope your patients find the relief they’re looking for. For more information on AJOVY, please consult the full Prescribing Information available at AJOVYhcp.com. We thank you for watching.

Patients experienced significantly more migraine-free days with AJOVY vs placebo in the HALO + Long-Term Extension Studies1,2

See Study Design

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Consider limitations of Long-Term Extension study design when interpreting efficacy results.

In episodic migraine, a reduction in monthly migraine days was demonstrated during the 12-week period (primary endpoint), with results seen as early as week 11,2

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Consider limitations of Long-Term Extension study design when interpreting efficacy results.

Patients randomized to quarterly dosing had a mean baseline of 13.2 headache days of at least moderate severity per month and experienced, on average1:
4.7 fewer headache days at month 3 vs 3.3 with placebo (P<0.001).1,2

Patients randomized to monthly dosing had a mean baseline of 12.8 headache days of at least moderate severity per month and experienced, on average1:
5.1 fewer headache days at month 3 vs 3.3 with placebo (P<0.001).1,2

*Reduction in monthly average number of headache days from the Long-Term Extension study was 6.8 with monthly dosing.2

Patients randomized to quarterly dosing had a mean baseline of 9.2 migraine days per month and experienced, on average1:
4.2 fewer migraine days at month 3 vs 3.1 with placebo (P<0.001).1,2

Patients randomized to monthly dosing had a mean baseline of 8.9 migraine days per month and experienced, on average1:
4.3 fewer migraine days at month 3 vs 3.1 with placebo (P<0.001).1,2

*Reduction in monthly average number of migraine days from the Long-Term Extension study was 5.1 with monthly dosing.2

In clinical trials, AJOVY reduced migraine days by 50% or more for some patients1

Secondary endpoint1

Reduction

in monthly number of migrane days with quarterly dosing

37.6% vs 18.1%

with placebo
(P<0.001)

Exploratory analysis2

Reduction

in monthly number of migrane days with quarterly dosing

20% vs 10.4%

with placebo
(Exploratory analysis)

Exploratory analysis2

Reduction

in monthly number of migrane days with quarterly dosing

7.7% vs 4.2%

with placebo
(Exploratory analysis)

Secondary endpoint1

Reduction

in monthly number of migrane days with quarterly dosing

44.4% vs 27.9%

with placebo
(P<0.001)

Exploratory analysis2

Reduction

in monthly number of migrane days with quarterly dosing

25.8% vs 15.4%

with placebo
(Exploratory analysis)

Exploratory analysis2

Reduction

in monthly number of migrane days with quarterly dosing

8.5% vs 4.5%

with placebo
(Exploratory analysis)

Similar reductions seen with monthly dosing in chronic migraine patients

With monthly dosing, reduction in monthly average headache days of at least moderate severity: 40.8% of patients achieved a ≥50% reduction vs 18.1% with placebo (P<0.001), 20.6% achieved a ≥75% reduction vs 10.4% with placebo (exploratory analysis), and 7.5% achieved 100% reduction vs 4.2% for placebo (exploratory analysis).1,2

Similar reductions seen with monthly dosing in episodic migraine patients

With monthly dosing, reduction in monthly average migraine days: 47.7% of patients achieved a ≥50% reduction vs 27.9% with placebo (P<0.001), 27.2% achieved a ≥75% reduction vs 15.4% with placebo (exploratory analysis), and 10.1% achieved 100% reduction vs 4.5% for placebo (exploratory analysis).1,2

What to explore next