SAN FRANCISCO — The sumatriptan 3-mg subcutaneous auto-injector (Zembrace SymTouch, Promius Pharma) approved by the US Food and Drug Administration (FDA) for acute treatment of episodic migraine, with or without, aura is well tolerated, safe, and effective, results from a large, double-blind, placebo-controlled trial show.

Compared with placebo and historical data for 6-mg sumatriptan pen injectors, the 3-mg auto-injector product (also known as DFN-11) fared well in terms of tolerability and efficacy in both the double-blind and open-label extension periods of the multicenter phase 3 study.

"The 'value proposition' of this product is it has the efficacy close to a gold-standard treatment, which is 6 mg. At the same time, it has a much lower rate of tolerability issues compared to historical data," lead investigator Sagar Munjal, MD, vice president and chief medical officer of Promius Pharma in Princeton, New Jersey, told Medscape Medical News.

The findings were presented here at the American Headache Society (AHS) Annual Meeting 2018.

Slow Uptick

"Despite the established efficacy of subcutaneous sumatriptan 6 mg, fewer than 10% of migraine sufferers use it. This may be due to triptan sensations and a high incidence of injection-site reactions," the investigators note.

The trial included a total of 268 individuals with episodic migraine for at least 12 months who averaged two to six attacks per month with no more than 14 headache days per month and at least 48 headache-free hours between attacks. Participants were randomly assigned 1:1 to receive DFN-11 or matching placebo.

During the double-blind treatment phase of the study participants were instructed to self-administer the auto-injector to treat one moderate-to-severe migraine attack and record their experience in a real-time e-diary.

The study's primary efficacy endpoint was the proportion of patients who were pain-free 2 hours after dosing.

Following the double-blind phase of the study, participants continued into an 8-week open-label period to further assess safety and tolerability of the study drug.

Of the 268 patients enrolled in the trial, postdose data were available for 208 patients, 104 in each study group.

Results showed the proportion of individuals who were pain-free 2 hours after injection was significantly higher in the active treatment group (51%) than in the placebo group (31%; P = .002).

In addition, pain relief at 2 hours after dosing was also reported by a significantly greater proportion of the 3-mg treatment group than the placebo group: 76% vs 61%, respectively (P = .018).

Table. Comparison of Migraine Attack Symptoms

Symptom 3 mg Sumatriptan (%) Placebo (%) P Value Freedom from most bothersome symptom at 2 h 64 48 .031 Relief of nausea 78 67 .179 Relief of photophobia 65 43 .006 Relief of phonophobia 70 50 .017

Safe, Tolerable

The purpose of the 8-week open-label extension phase of the study was to further assess safety and tolerability. In this phase of the study, 219 participants could use the auto-injector to treat up to four individual additional migraine attacks.

Thirty-three percent of the active treatment group and 13% of the placebo group reported treatment-emergent adverse events (TEAEs) in the double-blind period.

When asked to characterize this difference, Munjal said, "It's pretty low. The reason I say that is most TEAEs were associated with the auto injection; they account for 40% to 60% depending on what study you're looking at."

The most common TEAEs were injection site pain and injection site swelling. "If you remove the injection site reactions…it's a low-dose product where the number of AEs is much lower," he added.

"So safety was not an issue — it was really the injection site reactions driving up the numbers." In the double-blind phase, injection site reactions were reported by 22% of the 3-mg treatment group and 12% of the placebo group.

TEAEs occurred in 41% of participants in the open-label portion.

Two participants in the double-blind phase and five others in the open-label extension discontinued treatment because of adverse events. "No major safety issues were reported," Munjal said.

More User-Friendly

The investigators are not claiming superiority of the 3-mg product over the 6-mg products available on the market. Munjal cautioned that the study was not a head-to-head comparison. Instead, they assessed historical data published for the 6-mg auto-injectors.

For example, they assessed the rate of side effects associated with the triptan class, which can limit treatment in some patients. These effects included tingling or prickling; dizziness or vertigo; a warm or hot burning sensation or a cold sensation; pressure, tightness, or heaviness; paresthesia; and flushing or numbness within 2 hours of injection.

"We saw about 7% to 8% [rate] with the 3-mg product," Munjal said. "That is much lower than what is reported in the historical data, where it ranges anywhere from 25% to 75% in the first 2 hours."

In the double-blind phase of the study, 7.2% of the active treatment and 1.7% of the placebo group experienced a triptan-related side effect. Paresthesia was the most common in the 3-mg group at 2.7% and noncardiac chest discomfort among the placebo group at 1.7%. In the open-label phase, the overall rate was 11.4%.

Another advantage of the 3-mg sumatriptan auto-injector product, Munjal said, is that "above all, it's practical and user friendly."

"The feedback we got is that the products currently on the market sometimes hurt a lot and are not user-friendly," he said.

Commenting on the findings for Medscape Medical News, Elizabeth Loder, MD, MPH, chief of the Division of Headache and Pain the Department of Neurology at Brigham and Women's Hospital in Boston, Massachusetts, said that it's beneficial to explore the dose range.

"There are probably people who don't need 6 mg, and the lower doses appear tolerable, so as long as you have the efficacy, it's very nice," she said.

Promius Laboratories is a subsidiary of Dr. Reddy's Laboratories, which supported the study. Munjal is an employee at Promius. Loder has disclosed no relevant financial relationships.

American Headache Society (AHS) Annual Meeting 2018. Abstract IOR10. Presented June 30, 2018.

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