Erenumab Safe, Effective in Preventing Refractory Migraine

Damian McNamara

July 02, 2018

SAN FRANCISCO — The fully humanized monoclonal antibody erenumab (Aimovig, Novartis/Amgen) is safe and effective in preventing refractory episodic migraine, new research suggests.

Results of a randomized parallel-group study showed the drug was effective in patients with episodic migraine in whom two to four previous preventive medicines have failed, offering a potential solution to this real-world clinical challenge.

Compared to baseline, 30% of patients treated with erenumab achieved a 50% or greater reduction in mean migraine days during the third month of the 12-week Study Evaluating the Effectiveness of AMG 334 Injection in Preventing Migraines in Adults Having Failed Other Therapies (LIBERTY) study. In contrast, only 14% of the placebo recipients achieved this primary outcome, a significant difference.

Erenumab selectively targets the calcitonin gene-related peptide (CGRP) receptor, which is believed to play a prominent role in migraine. It is the first agent available in the new CGRP class following its May 17 approval for prevention of migraine by the US Food and Drug Administration.

"The bottom line is these new medicines still work. For the person who failed four preventives in the past, these medicines are just as likely to work or even more likely to work," study author Peter Goadsby, MD, from the University of California San Francisco, said during a media briefing here at the American Headache Society (AHS) Annual Meeting 2018.

"The chance they will work vs a placebo is just as good whether you've failed four previous medicines or if you've never had a preventive," he added.

Fewer Migraine Days

Investigators defined medication failures as lack of efficacy or lack of tolerance, common issues among people living with migraine.

"The doctor who is seeing patients with migraine has people lined up out the door who have failed two to four preventives, because that is who goes to a neurologist," Goadsby told Medscape Medical News.

At study entry, two preventives had failed in 39% of the 246 participants, three had failed in 38%, and four had failed in 23%.

The researchers randomly assigned 121 adults to once-monthly subcutaneous injections of erenumab 140 mg and another 125 to a placebo injection. After the 12-week treatment phase of the multicenter, double-blind study, all participants could receive erenumab during an open-label extension.

The mean age of participants was 44 to 45 years, and 80% of participants were women. At baseline, the mean monthly number of migraine days was 9.3.

At week 12, participants treated with erenumab were significantly more likely to achieve a 50% or greater reduction in mean migraine days than the placebo group (odds ratio [OR], 2.73).

A larger proportion of patients in the active treatment group than in the placebo group achieved a 75% or greater response rate, at 11.8% vs 4.0% (OR, 3.2). A 100% response rate was seen in 5.9% of the treatment group vs no one in the placebo group. The lack of complete response in the placebo group precluded calculation of an odds ratio.

"All results were highly statistically significant," Jan Klatt, clinical development lead at Novartis, said when presenting the 12-week double-blind treatment phase results at the conference. The secondary endpoints of the study were all met, he added

Table. Secondary Outcome Measures, Weeks 9 to 12

Outcome Measure Erenumab Group Placebo Group Mean Difference P Value
Monthly migraine days –1.8 –0.2 –1.6 .004
Migraine-specific medication days –1.3 0.5 –1.7 <.001
MPFID-Physical Impairment –1.9 1.6 –3.5 .003
MPFID-Everyday Activities –3.4 0.6 –3.9 <.001
MPFID = Migraine Physical Function Impact Diary.

 

Safety Data

The 140-mg erenumab dose was very similar to placebo in terms of safety, Klatt said. The proportion of participants experiencing any adverse event was 55% in the erenumab group and 54% in the placebo group. The most common adverse event reported in the erenumab group was injection site pain, in almost 6% of participants. No patients died during the study.

Three serious adverse events occurred in the study. The two that occurred in the treatment group included one patient hospitalized for a severe migraine who required diagnostic workup that did not show anything specific. The other patient had a traumatic fracture after being hit by a baseball.  

Ironically, Goadsby pointed out, patients in whom previous treatments have failed were somewhat avoided in the early phase of the CGRP monoclonal antibody studies. "There was the idea they might be more difficult to treat or more complex. Wrong."

"Erenumab is a potential novel treatment option for patients who failed prior preventive treatments," Klatt said.

"That is incredibly important," Goadsby said. "The people who are sitting at home now who can't get out because they've failed several medicines need to know these [new] medicines are there and are likely to work for them."

Commenting on the findings for Medscape Medical News, Andrew C. Charles, MD, a neurologist at UCLA Health in Los Angeles, California, who was not involved in the research, described the study as interesting and reflective of a real-world clinical issue.

"For those of us in headache specialty practice, the overwhelming majority of our patients fail multiple drugs by the time they get to see us. So it's exciting from that standpoint," he said

The CGRP antibody agents in development work through a novel mechanism, and they are pharmacologically different from other migraine treatments, Charles added. "None of the therapies we had in the past were specifically developed and designed for migraine. We borrowed them from other indications: seizure medicines, blood pressure medicines. Now that we have one developed based on the understanding of migraine biology…that's probably why we are seeing this response in people who failed previous medicines."

Novartis Pharmaceuticals sponsored the LIBERTY trial. Goadsby is a consultant and receives grants from Novartis. Klatt is a Novartis employee. Charles has disclosed no relevant financial relationships.

American Headache Society (AHS) Annual Meeting 2018. Abstract IOR-08. Presented June 30, 2018.

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