HAE therapy ADX-324 hits Phase 3 milestone with first treatment
Long-acting therapy aims to reduce swelling attacks with less frequent dosing
The first adult participant with hereditary angioedema (HAE) has been dosed in STOP-HAE, a Phase 3 clinical trial evaluating the efficacy of ADARx Pharmaceuticals’ investigational therapy ADX-324. Designed as a long-acting preventive treatment, ADX-324 aims to reduce the frequency of swelling attacks while requiring fewer injections.
The STOP-HAE (NCT06960213) trial is assessing ADX-324’s safety, tolerability, and effectiveness against a placebo in up to 90 adults with HAE type 1 or 2. Participants receiving ADX-324 are being treated with either 300 mg every six months or 240 mg every three months. After finishing the study, they will have the option to join a long-term open-label extension to continue receiving the therapy. The study currently enrolling at one site in Little Rock, Ark.
“Dosing the first patient in our ADX-324 Phase 3 clinical trial is a significant milestone for ADARx and we look forward to advancing this program for the HAE community,” Zhen Li, PhD, president and CEO of ADARx, said in a company press release.
Therapy also receives orphan drug designation
ADX-324 has also received orphan drug designation from the U.S. Food and Drug Administration (FDA) for HAE. This designation supports the development of rare disease therapies by offering benefits such as tax credits, fee waivers, and market exclusivity if approved.
“We believe the FDA’s orphan drug designation for ADX-324 underscores the continued need for additional treatment options and highlights the potential of ADX-324 to provide extended attack-free periods with substantially reduced dosing frequency,” Li said.
HAE is a type of angioedema caused by genetic mutations that lead to a faulty or missing protein called C1 inhibitor. Without the C1 inhibitor, an enzyme called kallikrein becomes overactive and triggers the release of another molecule called bradykinin. Excess bradykinin causes blood vessels to leak fluid into tissues, making them swell.
Despite available treatments, “most HAE patients remain at risk of breakthrough attacks and do not achieve sustained, long-term attack-free control. In addition, the currently approved prophylaxis [preventive] treatments require monthly or more frequent injections,” Li said.
ADX-324 is a small interfering RNA (siRNA) therapy designed to inhibit the production of prekallikrein (PKK) — a protein that acts as a precursor to kallikrein. By reducing circulating levels of kallikrein, the therapy may prevent the release of bradykinin. This approach could help control swelling for longer periods with fewer doses than existing preventive treatments.
The Phase 3 clinical program follows a two-part Phase 1/2 clinical trial (NCT05691361) launched in early 2023. Data from healthy adults and patients showed ADX-324 achieved significant and durable reduction of PKK over at least three months compared with a placebo, while being safe and well tolerated.
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