Regulatory & Policy

ADARx's onvuzosiran secures FDA Fast Track for twice-yearly HAE prophylaxis approach

ADARx's onvuzosiran secures FDA Fast Track for twice-yearly HAE prophylaxis approach

San Diego-based ADARx Pharmaceuticals, Inc. received US FDA Fast Track Designation for onvuzosiran (ADX-324), a prekallikrein (PKK)-targeting small interfering RNA (siRNA) therapeutic candidate, for prophylaxis to prevent attacks of hereditary angioedema (HAE). The designation, announced August 24, 2026, applies to onvuzosiran's ongoing evaluation in the Phase III STOP-HAE trial (NCT06960213) and follows an orphan drug designation granted in October 2025 for the treatment of hereditary angioedema (HAE).

The designation was granted based on the data generated to date, including Phase I/II data presented in February 2026 at the American Academy of Allergy, Asthma & Immunology (AAAAI) Annual Meeting. In the Phase I portion, 43 healthy participants received single ascending doses of onvuzosiran (0.4 mg/kg to 6 mg/kg) or placebo; the 300 mg dose produced a 93% reduction in plasma kallikrein levels at nadir, with suppression of ≥80% maintained through Day 169, supporting a twice-yearly dosing interval. In the Phase IIa cohort — three HAE patients receiving subcutaneous onvuzosiran every six months — kallikrein reductions were comparable to those seen in Phase I, and no HAE attacks were observed in patients who maintained ≥80% kallikrein suppression. No serious adverse events were reported and there were no treatment-related discontinuations across the Phase I/II study.

Fast Track status enables ADARx to hold more frequent meetings with the FDA during the STOP-HAE trial, submit a New Drug Application (NDA) on a rolling basis, and qualify for priority review if relevant criteria are met.

Intellia Therapeutics' lonvoguran ziclumeran (lonvo-z), a single-infusion in vivo CRISPR therapy targeting the KLKB1 gene, reported a 91% reduction in moderate and severe HAE attacks in its Phase III HAELO trial and is advancing a rolling biologics license application (BLA) with the FDA, targeting a US launch in the first half of 2027.

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Approved prophylactic therapies include Takeda's lanadelumab (Takhzyro), typically dosed every two weeks with every-four-week dosing available for some well-controlled patients; CSL Behring's garadacimab (Andembry), dosed monthly; and Ionis Pharmaceuticals' donidalorsen (Dawnzera), dosed every four weeks with every-eight-week dosing available after six months in well-controlled patients. ADARx is developing onvuzosiran for dosing as infrequently as once every six months.

The Phase III STOP-HAE trial is enrolling approximately 90 adults with Type I and Type II HAE, randomized to onvuzosiran 300 mg every six months, onvuzosiran 240 mg every three months, or placebo, with a long-term open-label extension for completers. No data readout timeline has been disclosed publicly.


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