PHVS416 found to quickly ease HAE swelling symptoms in trial

Treatment on demand worked within hours of angioedema attack

Marisa Wexler, MS avatar

by Marisa Wexler, MS |

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Two hands, a stethoscope, and a handful of oral medications surround a clinical trial graph showing positive results.

On-demand treatment with the experimental oral therapy PHVS416 was found to quickly and effectively ease symptoms of swelling attacks for people with hereditary angioedema (HAE) in a Phase 2 clinical trial.

PHVS416 worked within hours of dosing, providing “clinical meaningful” reductions in swelling symptoms, according to researchers.

Pharvaris, the company developing the therapy, presented findings from the trial at the European Academy of Allergy and Clinical Immunology (EAACI) Hybrid Congress 2023, held in Germany earlier this month. The poster was titled, “Treatment with Oral Administered Bradykinin B2 Receptor Antagonist Deucrictibant Immediate-Release Capsule (PHVS416) Improves Hereditary Angioedema Attack Symptoms.”

“The results from the Phase 2 RAPIDe-1 clinical study show that treatment of an HAE attack with PHVS416 (deucrictibant immediate-release capsules) resulted in rapid and clinically meaningful improvement in symptoms as compared to placebo,” Peng Lu, MD, PhD, chief medical officer of Pharvaris, said in a company press release, adding that this outcome in the PHVS416 trial “supports its further development as a potential on-demand therapy for HAE.”

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In HAE, swelling attacks are triggered by excess levels of a signaling molecule called bradykinin. PHVS416 is an immediate-release oral therapy containing deucrictibant (previously called PHA121), a molecule that blocks a protein receptor for bradykinin. It works to halt the cascade of events leading to swelling attacks in patients.

Pharvaris conducted a Phase 2 clinical trial, dubbed RAPIDe-1 (NCT04618211), that tested several doses of PHVS416 against a placebo for on-demand treatment of HAE swelling attacks. Over the course of the study, 62 patients experienced 147 swelling attacks that were managed with on-demand treatment.

Results from the trial, announced earlier this year and also discussed in a separate poster at the EAACI congress, showed that PHVS416 outperformed a placebo at easing attack symptoms, as measured by a visual analogue scale (VAS-3). The therapy also reduced the need for other medications to control swelling.

“The study met the primary and all key secondary endpoints, providing evidence for the efficacy and tolerability of PHVS416 in treating HAE attacks,” Lu said.

Clinical meaningful improvement of symptoms was observed during the first hours after treatment with [PHVS416].

As secondary outcomes in the RAPIDe-1 trial, researchers assessed how treatment with PHVS416 affected the Mean Symptom Complex Severity (MSCS) score and the Treatment Outcome Score (TOS).

MSCS measures the severity of symptoms on a scale from 0 (normal) to 3 (severe), calculated as an average score across all body parts affected.

Results showed that, within four hours of taking PHVS416 at any dose tested, average MSCS scores decreased by more than 0.6. By comparison, for patients given the placebo, scores decreased by about 0.3, which is considered the minimum difference that’s clinically meaningful on this scale.

TOS assesses a patient’s response to treatment on a score from 100 (significant improvement) to -100 (significant worsening). For those given a placebo, average TOS remained at around zero at four hours after dosing, suggesting the placebo didn’t have any effect on symptoms, as expected. By contrast, for patients given PHVS416 at any tested dose, average TOS was higher than 50 at the same time point. For context, a change of 30 points on TOS is considered clinically relevant.

“Clinical meaningful improvement of symptoms was observed during the first hours after treatment with [PHVS416],” the researchers wrote.

Analyses of TOS over time suggested that most patients given PHVS416, at any of the tested doses, started experiencing symptom relief at about two hours following dosing. In most individuals, symptoms had completely or almost fully resolved within 4-5 hours after dosing.

“When asked to identify the most important factor in selecting an on-demand therapy, both people living with HAE and their treating physicians indicated that rapidity to onset of symptom relief and complete symptom relief were essential,” said Wim Souverijns, PhD, chief community engagement and commercial officer at Pharvaris.

Souverijns said the company’s own research identified several factors for why not all HAE attacks are “treated in a timely manner or treated at all, as is recommended by international clinical guidelines.”

Those reasons, Pharvaris found, include fear of pain with injection therapies, anxiety over whether a treatment can fully resolve attack symptoms in a single dose, and a “lack of confidence in the speed of symptom relief,” he said.

“An effective oral therapy that provides rapid and complete symptom relief could address some of these barriers,” Souverijns said.