Data Readout

Astria's navenibart Phase 3 in HAE heads toward a 2026 readout

ALPHA-ORBIT will test whether navenibart's early attack-reduction data hold up placebo-controlled in the only Phase 3 plasma kallikrein program in hereditary angioedema.

By AppliedXLJuly 13, 2026Trial NCT06842823

Executive Summary

Astria Therapeutics is running the pivotal trial that must reproduce, under placebo control, the attack-reduction signal it reported from earlier proof-of-concept data.
The trial is proceeding on protocol with no completion-date slippage or enrollment change, so the story is the pending result, not execution risk.
Navenibart is the only plasma-kallikrein-targeting asset to reach Phase 3 in hereditary angioedema, placing it ahead of same-target rivals still in earlier-phase testing.
A result that reproduces the early attack-reduction magnitude against placebo would move navenibart's dosing-interval pitch from proof-of-concept to registration-grade evidence.

The trial

NCT06842823, known as ALPHA-ORBIT, is a registrational Phase 3 study of navenibart (also called STAR-0215) in adults and adolescents with hereditary angioedema types 1 and 2. The trial randomizes patients across five arms, four experimental and one placebo comparator, and measures the primary endpoint as the number of time-normalized, investigator-confirmed HAE attacks during a 6-month treatment period. Secondary endpoints include quality-of-life scores, attacks requiring on-demand treatment, and the proportion of patients with a 50%, 70%, or 90% reduction in attack rate versus placebo. The trial targets enrollment of 145 patients across sites in 24 countries and has been enrolling since March 2025. NCT06842823

Probability of Success

Endpoint Met95%

Completes90%

Clinical Significance29%

Regulatory92%

The prior signal

Astria's case for navenibart rests on earlier Phase 1b/2 data. The company reported in March 2024 that navenibart dosed once or twice over six months cut monthly HAE attack rates by 90-96%, with a 92-100% decrease in moderate or severe attacks and a 91-95% reduction in attacks requiring rescue medication, and no serious adverse events or discontinuations. Chief Executive Officer Jill C. Milne said at the time that the safety and tolerability profile, with no injection pain observed, supported dosing navenibart every three or six months. ALPHA-ORBIT is the placebo-controlled test of whether that open-label signal reproduces under randomization. Astria

Operational status

The trial's registry history shows two status changes: from Not yet recruiting to Recruiting in March 2025, and from Recruiting to Enrolling by invitation in June 2026. Enrollment has stayed flat at its original target of 145 patients, a change the operational risk model reads as within the routine band since it flags moves of 20% or more. The primary completion date has not shifted from March 1, 2027, and the trial has logged one eligibility-criteria amendment with no endpoint changes, a pattern that reads as a stable, on-track registrational program rather than one under operational strain. NCT06842823

The field

Navenibart is the only Phase 3 asset targeting plasma kallikrein in hereditary angioedema; the nearest same-target peers, including KalVista's feniralstat, are still in Phase 2, and Ionis's donidalorsen and Takeda's lanadelumab work through different modalities within the same target class in earlier-stage or already-approved settings. Within Plasma Kallikrein Inhibitor programs broadly, 7 of 8 Phase 3 trials in hereditary angioedema and related targets have completed and 1 was terminated. The trial's own guided 2026 top-line window has stayed consistent across four sponsor updates issued between May 2024 and December 2024, with no revision to the year-end target. Astria

What the readout will test

A blended registry-and-model forecast puts the point estimate for this readout at October 10, 2026, with a 58% probability of landing within 180 days of that date, though the primary completion date is not until March 2027. Because the trial is randomized and placebo-controlled, the design can produce a decision-grade efficacy read rather than an open-label impression. The bar this readout must clear is straightforward: reproduce, against placebo, an attack-rate reduction consistent with what the open-label proof-of-concept data suggested, since a drift back toward a smaller effect would be the notable surprise given how much of navenibart's positioning already rests on the earlier numbers. NCT06842823+1

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