Astria Begins Phase 3 ALPHA-ORBIT Trial of Navenibart for Hereditary Angioedema
Astria Therapeutics, Inc. (Nasdaq: ATXS), a leading biopharmaceutical company dedicated to developing innovative therapies for allergic and immunological diseases, has officially launched the Phase 3 ALPHA-ORBIT clinical trial of navenibart for individuals living with hereditary angioedema (HAE). This pivotal study aims to assess the efficacy and safety of navenibart, a treatment designed to prevent HAE attacks with minimal dosing requirements, offering patients a significant reduction in treatment burden with administration options of every three months (Q3M) or every six months (Q6M).
Christopher Morabito, Chief Medical Officer of Astria Therapeutics, expressed optimism about the study’s potential outcomes, stating, “We are confident that navenibart will deliver high efficacy, low treatment burden, and favorable safety and tolerability, and we are pleased to have initiated our Phase 3 ALPHA-ORBIT trial to support this vision. The Phase 3 program is designed to provide options, giving patients and physicians the ability to decide what works best for them by administering navenibart as few as 2 or 4 times per year.”
The launch of this trial marks a crucial step forward in addressing the needs of individuals with HAE, a rare and potentially life-threatening genetic disorder characterized by recurrent episodes of severe swelling in various parts of the body, including the limbs, face, intestinal tract, and airway. Conventional treatment options often require frequent administration, placing a significant burden on patients. Navenibart’s extended dosing schedule has the potential to offer patients greater freedom and improved quality of life.
Dr. Aleena Banerji, Clinical Director of the Allergy and Immunology Unit at Massachusetts General Hospital (MGH) and principal investigator of the ALPHA-ORBIT study, emphasized the importance of patient-centric treatment solutions: “Patients have told us that it would be extremely important to have a treatment that would allow them to live their lives without the constraints of HAE. Navenibart has been shown to prevent HAE attacks by administering infrequent doses, which could allow patients to spend less time managing their disease.”
ALPHA-ORBIT is a global, randomized, double-blind, placebo-controlled Phase 3 clinical trial that will evaluate navenibart’s safety and efficacy over a six-month treatment period. The trial will enroll 135 adult participants and 10 adolescent participants (who will receive open-label treatment) with type 1 or type 2 HAE. The study design incorporates multiple dosing regimens, providing flexibility to meet diverse patient needs. Adult patients will be randomly assigned to one of four groups:
- An initial dose of 600 mg followed by 300 mg Q3M
- 600 mg Q6M
- 600 mg Q3M
- Placebo
Adolescent participants will receive an initial dose of 600 mg followed by 300 mg Q3M. By implementing different dosing schedules, Astria aims to optimize treatment regimens to suit individual patient preferences and medical requirements.
The study’s primary endpoint will assess the number of monthly HAE attacks normalized over a six-month period, while a key secondary endpoint includes the proportion of participants who remain attack-free at six months. The trial is expected to generate top-line results by early 2027, offering valuable insights into navenibart’s long-term efficacy and potential role in redefining the standard of care for HAE.
Beyond ALPHA-ORBIT, patients completing the six-month treatment period may be eligible to enroll in a long-term extension study known as ORBIT-EXPANSE. This follow-up trial will allow all participants to receive navenibart in an open-label setting, with a flexible dosing regimen tailored to individual needs. The combined Phase 3 program, comprising both ALPHA-ORBIT and ORBIT-EXPANSE, is structured to support global regulatory submissions for navenibart.
The decision to advance to Phase 3 trials follows promising results from the earlier Phase 1b/2 ALPHA-STAR study. In that study, navenibart demonstrated rapid and sustained efficacy, with a favorable safety and tolerability profile. The pharmacokinetics and pharmacodynamics of navenibart supported its ability to achieve sustained inhibition of plasma kallikrein, a key mediator of HAE attacks. The treatment achieved a reduction in mean monthly attack rates by 90-95% and a seizure freedom rate of up to 67% over a six-month period.
Hereditary angioedema is a rare disorder that affects an estimated 1 in 50,000 people worldwide. It is caused by a deficiency or dysfunction of C1 inhibitor protein, leading to excessive bradykinin production, which in turn causes fluid leakage from blood vessels and results in swelling episodes. These episodes can be painful, disfiguring, and, in some cases, life-threatening if they affect the airway. Despite advancements in HAE management, there remains a significant need for therapies that offer both strong protection against attacks and a low treatment burden.
Navenibart belongs to a class of therapies targeting plasma kallikrein, an enzyme responsible for the excessive bradykinin production that leads to HAE attacks. By inhibiting plasma kallikrein, navenibart has the potential to prevent these attacks more effectively and with fewer doses than existing treatments. Current standard-of-care therapies for HAE include on-demand treatments to stop acute attacks and prophylactic therapies to reduce attack frequency. However, many available prophylactic options require frequent dosing, invasive administration methods, or come with significant side effects, creating a demand for improved alternatives.
The innovative design of the ALPHA-ORBIT trial underscores Astria Therapeutics’ commitment to patient-centered research. By incorporating multiple dosing regimens and prioritizing flexibility, the study aims to provide real-world insights into how navenibart can best serve patients’ needs. If successful, this therapy could significantly enhance the quality of life for individuals living with HAE by reducing both the frequency of attacks and the overall burden of treatment.
Astria Therapeutics encourages patients and healthcare providers to learn more about the ALPHA-ORBIT trial through the study’s official websites: AlphaOrbit.longboat.com, astriatrials.com, and clinicaltrials.gov (NCT06842823). The company remains committed to advancing its clinical programs and bringing transformative therapies to individuals with rare allergic and immunological diseases.
As the ALPHA-ORBIT trial progresses, Astria Therapeutics will continue to provide updates on its findings, with the goal of securing regulatory approval and making navenibart widely available to patients who need it. With the potential to redefine HAE management, navenibart represents an important advancement in the field of rare disease therapeutics, promising greater efficacy, safety, and convenience for patients worldwide.
