麻豆传媒

Calcium-channel blocker nasal spray etripamil flopped for rapid conversion of paroxysmal supraventricular tachycardia (PSVT) in its pivotal phase III trial, but the story may not be over for the novel agent.

The novel agent did not meet the primary endpoint of conversion over 5 hours compared with placebo when self-administered in a medically non-supervised setting (HR 1.086, 95% CI, 0.726-1.623), Bruce Stambler, MD, of Piedmont Heart Institute in Atlanta, reported at the .

"While we were disappointed that the magic P-value was not reached, we do remain optimistic. This study is ongoing, and a future study looking at an earlier primary endpoint is actually being developed and designed in consultation with the FDA," said Stambler in a media briefing prior to the presentation of the study results.

The mean time to conversion was 25 minutes in the etripamil group versus 50 minutes in the placebo group, a "clinically meaningful" difference per the researchers. "It has its peak effect in 5 to 10 minutes, and a decline in the next 35 minutes," Stambler said.

"The drug is not expected to have pharmacological effects beyond 45 minutes to an hour," Stambler said. "The 5-hour endpoint was chosen primarily to get safety data."

The ad-hoc analysis findings about the drug's early effects (HR 1.668 conversion within 45 minutes, 95% CI 1.026-2.712) are promising, he said. Another study is planned to "analyze the first hour or first 45 minutes to confirm what was observed."

While the ad-hoc analysis findings are promising, "likely there is a need for a long-acting form of medications after the initial conversion with etripamil," commented Dhrubajyoti Bandyopadhyay, MBBS, MD, of the Icahn School of Medicine at Mount Sinai/St. Luke's Roosevelt in New York City.

Adrija Hajra, MBBS, MD, of the Jacobi Medical Center/Albert Einstein College of Medicine in New York City, cautioned that "we still need more data to find out any long-term adverse effects of this new molecule. Also, as its effect is short-lasting, we need to see if it can be administered repeatedly to get the sustained effect without having any adverse reactions. And these patients often are on multiple medications, so we need to be vigilant about drug interactions."

A niche for this drug could be "the patient with very infrequent episodes who does not want to undergo catheter ablation or a patient who has had only a single episode and would prefer a conservative approach," predicted Fred Kusumoto, MD, director of heart rhythm services at Mayo Clinic in Jacksonville, Florida.

The phase III, industry-funded NODE-301 trial randomly assigned patients with a history of PSVT to etripamil or placebo at a 2:1 ratio, given in a double-blind manner. There were 431 patients in the safety group (mean age 55, female 63%).

Of the nearly 200 patients with self-administered doses after suspected episodes of spontaneous PSVT, 107 incidents in the etripamil group were determined to be PSVT compared with 49 incidents in the placebo group.

According to Stambler, the drug is safe and well-tolerated. "The most common side effects were nasal discomfort and congestion, typically transient in nature and mild in severity," he said.

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