Effectiveness of Rimegepant Further Displayed in Pooled Phase 3 Analysis

Stewart Tepper, MD

Rimegepant (Nurtec ODT; Pfizer) is a calcitonin gene-related peptide (CGRP) receptor antagonist approved for the acute treatment of migraine with or without aura in adults, and for the preventive treatment of episodic migraine in adults. The therapy, which has been on market since 2020, is available as an orally disintegrating tablet, which offer convenience and a potentially faster response time than the conventional tablet formulation.

Recently, at the 2024 Migraine Trust International Symposium meeting, held September 5-8 in London, England, investigators presented a pooled analysis of 4 randomized placebo-controlled trials assessing rimegepant in the acute treatment of migraine. These studies, which included 2439 patients on rimegepant and 2456 on placebo, included adults who had at least 1-year history of migraine, 2-8 migraine attacks of moderate or severe pain intensity per month, and attacks that lasted 4-72 hours if untreated.

Results showed that treatment with rimegepant 75 mg once daily outperformed placebo on the co-primary end points of pain freedom and freedom from the most bothersome symptom at 2 hours. Rimegepant was also considered safe, as nausea was the only reported adverse event found in more than 1% of treated patients. Following these results, lead investigator Stewart Tepper, MD, vice president at the New England Institute for Neurology and Headache in Stamford, Connecticut, provided perspective on what the data means. Tepper, a headache specialist, spoke about the notable takeaways, improvements in how to efficiently use and prescribe rimegepant, as well as ways to optimize CGRP-targeting treatment. Furthermore, he spoke on the noted impacts of rimegepant on rescue medication use and what this brings to patients with acute migraine.

NeurologyLive: What was the premise behind this analysis? What additive value does it bring?

Stewart Tepper, MD: This analysis aimed to summarize the efficacy and safety of rimegepant for acute treatment of migraine using pooled data from nearly 5,000 participants (n=4,895) across four randomized placebo-controlled trials.

In terms of additive value, to pool data from multiple studies increases the generalizability of the findings, allowing for a more comprehensive understanding of rimegepant across international study populations.

Among the findings, what are the most notable takeaways?

Rimegepant demonstrated statistically significant benefits over placebo across all efficacy endpoints, including the co-primary endpoints of pain freedom 2 hours post-dose (20.0% vs 11.8%; p<0.0001) and most bothersome symptom freedom 2 hours post-dose (40.2% vs 29.2%; p<0.0001).

However, only highlighting therapeutic gain over placebo doesn’t tell the full story. It’s also important to consider adverse events, which were remarkably low with rimegepant across the four studies.

The secondary endpoints were consistently positive as well. Combined with the safety and tolerability data, this creates an impressive presentation that highlights the consistent efficacy, safety, and tolerability of rimegepant. That is the most important aspect of this analysis to me.

From a prescribing perspective, are there any ways to optimize rimegepant treatment? How do we ensure that the right patients get the most benefit out of this therapy?

The discussion around optimizing rimegepant treatment differs from that of other migraine therapies because rimegepant is the only medication approved for acute and preventive treatment of migraine. This study summarized data from a very large cohort of patients using rimegepant for acute treatment, but we also have randomized controlled trials and open-label safety extension data for its preventive use.

To maximize the benefits of rimegepant, we recommend three main strategies:

1. Early Intervention: Instruct patients to use rimegepant very early in a migraine, even before pain begins, during the prodrome or aura phases. Early use increases the likelihood of achieving pain freedom, and there is nota therapeutic penalty in terms of side effects.
2. Consistent Use: Suggust to patients to treat each migraine headache with rimegepant. According to the 201 study results that Robert Croop published earlier this year, the more they treat with rimegepant, the less headache they have.
3. Flexibility: Patients can move between preventive and acute treatment with rimegepant. Patients can use rimegepant early for acute treatment of migraine for benefit without side effects. Then, during periods of vulnerability, they can switch to taking it every other day for prevention before reverting to acute treatment as needed when clinically appropriate.

This flexibility helps to optimize the overall effectiveness of rimegepant treatment.

How important is it to see reductions in rescue medication use? What does this suggest?

The prolonged benefit of rimegepant, including sustained pain relief and pain freedom, leads to a reduction in the use of other acute and rescue medications. As the use of these medications decreases, the risk of transformation to medication overuse headache and chronic migraine also decreases. Additionally, reduced rescue medication use is also likely associated with lower levels of disability and impact from migraine.

In this analysis, 15.5% of participants in the rimegepant group used rescue medication within 24 hours post-dose, compared with 28.9% in the placebo group. This significant reduction is important, as it provides strong evidence that acute use of rimegepant is likely associated with decreased likelihood of transformation to medication overuse headache and chronic migraine.

Over the coming years, how will we continue to improve the use of CGRP-targeting treatments like rimegepant?

The use of CGRP-targeting treatments, both acutely and preventively, matches patient needs. Older preventive medications often have high discontinuation rates due to side effects and limited efficacy. For that reason, the American Headache Society published a position paper in March 2024 suggesting that CGRP-targeting treatments should be considered for first-line preventive use. This is increasingly happening in the United States, and similar recommendations were published in 2024 by the Polish Headache Society.

On the acute side, while the AHS has not yet taken a position, I anticipate a similar recommendation; when older acute treatments have failed or are contraindicated, patients should move to gepants rapidly. A 2024 consensus statement from experts in the UAE suggested that CGRP-targeting treatments should be considered first-line for acute migraine treatment.

In the coming years, I expect an increase in earlier use of CGRP-targeting, migraine-specific treatments for both acute and preventive migraine treatment, which will lead to reductions in healthcare resource utilization and improvements in patient quality of life.