HAE attacks start resolving in under 30 minutes with PHVS416 in trial

Pharvaris' capsule is immediate-release formulation of deucrictibant

Marisa Wexler, MS avatar

by Marisa Wexler, MS |

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In a clinical trial, most people with hereditary angioedema (HAE) given on-demand treatment with PHVS416, an immediate-release capsule formulation of deucrictibant, saw swelling attacks begin to resolve within half an hour of taking the medication.

That’s according to new data presented in a poster, titled “Deucrictibant immediate-release capsule reduces time to end of progression of hereditary angioedema attacks’ manifestations,” at the the American College of Allergy, Asthma & Immunology (ACAAI) 2023 Annual Scientific Meeting, held in Anaheim, California. The work was funded by Pharvaris, the company developing the therapy.

Treatment with PHVS416 also substantially reduced patients’ use of rescue medication, according to Pharvaris.

“Results of the post-hoc RAPIDe-1 analysis provide additional evidence on the rapid onset of effects of PHVS416 for on-demand treatment of HAE attacks,” Peng Lu, MD, PhD, chief medical officer of Pharvaris, said in a company press release.

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RAPIDe-1 trial tested PHVS416 in 147 HAE attacks

HAE is characterized by overproduction of the signaling molecule bradykinin, which binds to receptors in blood vessels to trigger the release of fluid, leading to swelling attacks. Deucrictibant, the active agent in PHVS416, is designed to stop HAE-related swelling by blocking bradykinin’s B2 receptors.

Pharvaris conducted a Phase 2 clinical trial called RAPIDe-1 (NCT04618211) to test PHVS416 as an on-demand treatment for HAE attacks. In the study, 62 HAE patients experienced a total of 147 swelling attacks, for which they were given either PHVS416 at one of three doses, or a placebo. Results from the trial, completed in March, showed that the experimental therapy was more effective than the placebo at controlling swelling.

Now, scientists conducted a post hoc analysis of data from the RAPIDe-1 study — meaning an analysis designed and carried out after the study was already done and all the data were available.

The scientists specifically were interested in the time it took for patients receiving on-demand treatment to experience end of progression, or EoP. That’s the first point where swelling stops getting worse, which the scientists said is “the initial evidence of attacks starting to evolve towards relief and resolution.”

For patients given PHVS416 at any of the tested doses, the median time to EoP was about 25 or 26 minutes, the results showed. Within about one hour of treatment with PHVS416, roughly three-quarters of patients given the experimental therapy had experienced EoP. At the highest tested dose (30 mg), more than 90% of patients had achieved EoP within 24 hours of treatment.

By comparison, among patients given the placebo, less than one-third had reached EoP after 24 hours.

The scientists concluded that “treatment of HAE attacks with [PHVS416] reduced the time to achieve EoP of attacks’ clinical manifestations.”

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Patients say treatments now take too long to work

In a separate poster presented at the ACAAI meeting, scientists at Pharvaris and other institutions reported the results of a survey done to better understand HAE patients’ attitudes toward currently available on-demand treatments for angioedema.  That poster was titled “Understanding the reasons not to treat all HAE attacks and satisfaction for on-demand treatment: physician- and patient-reported data.”

The team had surveyed 73 physicians caring for 310 HAE patients — among whom 58 provided self-reported data.

These results showed that most patients and clinicians overall are satisfied with current on-demand treatments, though nearly half of patients reported being dissatisfied with how such therapies are administered.

Moreover, almost 1 in 3 patients said they were dissatisfied with how long it takes current on-demand treatments to resolve attacks.

On-demand treatment taking too long to work was the most commonly reported reason that patients said they had not treated a recent attack.

Newer therapies with differential modes of administration and faster onset of action may encourage more consistent and timely treatment of HAE attacks and improved treatment satisfaction.

“These data highlight a lack of satisfaction with current [on-demand treatment] regarding [route of administration] and the portability of current devices,” the researchers wrote.

“Newer therapies with differential modes of administration and faster onset of action may encourage more consistent and timely treatment of HAE attacks and improved treatment satisfaction,” the team concluded.

Pharvaris is still running an extension study, called RAPIDe-2 (NCT05396105), that’s continuing to collect data on the use of PHVS416 as an on-demand treatment. The company also plans to launch a Phase 3 study next year to further test the on-demand treatment.

“The real-world HAE data and post-hoc analysis of RAPIDe-1 data … support the compelling story for the ongoing development of PHVS416 for the on-demand treatment of HAE,” Lu said.

“People living with HAE most frequently reported not treating attacks due to existing therapies taking too long to resolve the attack and injection-site reactions. An oral therapy with a faster onset of action may encourage more consistent and timely treatment of HAE attacks and improved treatment satisfaction,” Lu said.

A new trial called CHAPTER-1 (NCT05047185) — testing deucrictibant as a prophylactic or preventive treatment for HAE — also recently completed enrollment.