Phase 3 trial tests navenibart across 10 EU nations
Enrollment starts for adults, adolescents as long-term extension launches
Patient enrollment has started at sites in the European Union for a global Phase 3 clinical trial evaluating the safety and efficacy of navenibart, an antibody-based therapy designed to prevent swelling attacks in people with hereditary angioedema (HAE).
Dubbed ALPHA-ORBIT trial (NCT06842823), the pivotal trial is testing the Astria Therapeutics treatment in up to 145 adults and adolescents with HAE type 1 or 2. The trial’s approval by the European Medicines Agency (EMA) includes the activation of 32 sites in 10 EU countries.
Enrollment is ongoing at sites across North America, the EU, the U.K., South Africa, Hong Kong, Japan, North Macedonia, and Israel. Top-line results are expected in 2027, and if positive, they may serve as the basis for navenibart’s approval.
“We’re thrilled to be enrolling eligible participants in the EU for the Phase 3 ALPHA-ORBIT trial,” Christopher Morabito, MD, chief medical officer at Astria Therapeutics, said in a company press release. “The excitement we’re seeing from physicians and patients in the EU underscores navenibart’s potential to change the way people live with HAE across the globe.”
Long-term extension study launched
The company also announced the initiation of ORBIT-EXPANSE (NCT07204938), a long-term extension study in which eligible patients may continue receiving navenibart for up to two years after completing ALPHA-ORBIT.
“The entrance of eligible and interested participants into the ORBIT-EXPANSE long-term trial following the completion of the pivotal Phase 3 ALPHA-ORBIT trial highlights enthusiasm for navenibart, and we are deeply grateful to trial participants and site facilitators for their continued partnership,” Morabito said in a separate company press release.
HAE types 1 and 2 are caused by mutations that lead to a deficiency or dysfunction in a protein called C1 esterase inhibitor (C1-INH). This, in turn, leads to the overactivation of an enzyme called kallikrein and to the excessive production of bradykinin, a signaling molecule that drives the swelling attacks that characterize HAE.
Navenibart is an antibody-based therapy designed to block the activity of kallikrein, which is expected to reduce bradykinin levels and help prevent swelling attacks.
The treatment was well tolerated and able to reduce the rate of monthly swelling attacks by up to 95% in a Phase 1b/2 clinical trial called ALPHA-STAR (NCT05695248).
In an open-label extension study called ALPHA-SOLAR (NCT06007677), treatment with navenibart every three to six months reduced the monthly rate of HAE attacks by a mean of 92% over 10.1 months of follow-up.
The ALPHA-ORBIT study is expected to enroll up to 135 adults and 10 adolescents. Adults will be randomly assigned to receive a placebo, or one of three navenibart dosing regimens — 600 mg given every three or every six months, or 300 mg given every three months after an initial dose of 600 mg — via subcutaneous (under-the-skin) injections.
All adolescents will receive navenibart, at an initial dose of 600 mg, followed by 300 mg every three months.
The trial’s main goal is to assess changes in the number of swelling attacks occurring over the course of six months. Changes in the number of moderate or severe attacks and those requiring on-demand treatment, as well as patients’ quality of life, will also be evaluated.
After completing the trial, patients may continue treatment with navenibart in ORBIT-EXPANSE. After an initial six-month period in which they will receive the therapy at a fixed dose every three to six months, they may move from one regimen to another based on their needs.
“People living with HAE are waiting; not just for treatments that reduce the burden of disease, but for those that also ease the burden of treatment,” said Maria Kortekaas, president of HAE Netherlands. “Clinical trials are part of the promise of progress, and we are pleased that Astria has chosen to conduct this late-stage trial in numerous countries throughout Europe.”
About the Author
