What Is navenibart?
navenibart is an investigational drug currently being studied in clinical trials. It is being developed by Astria Therapeutics, Inc. for the treatment of Hereditary Angioedema (HAE). Based on current trial descriptions, navenibart is administered as a subcutaneous injection, meaning it is given under the skin. The specific mechanism by which navenibart works to treat HAE is not detailed in the provided trial information, but it is being evaluated for its potential to manage this condition.
There are currently 3 clinical trials investigating navenibart, with a total enrollment of 319 participants. The first trial began on January 23, 2023, and the latest trial is expected to conclude on October 3, 2025.
Uses and Conditions Under Study
navenibart is currently under investigation for the treatment of Hereditary Angioedema (HAE). HAE is a rare genetic disorder characterized by recurrent episodes of severe swelling in various parts of the body, including the skin, gastrointestinal tract, and airways. These swelling attacks can be painful, disfiguring, and potentially life-threatening if they affect the throat.
All 3 clinical trials for navenibart are focused on understanding its safety and effectiveness in managing HAE. Researchers are exploring how navenibart, administered as a subcutaneous injection, might help prevent or reduce the severity of these swelling attacks. The trials are sponsored by Astria Therapeutics, Inc. and include both recruiting and completed studies to gather comprehensive data on the drug's impact on patients with HAE.
The studies aim to determine if navenibart can offer a new therapeutic option for individuals living with this challenging condition.
Dosing
navenibart is administered as a subcutaneous injection, sometimes specifically referred to as a subcutaneous bolus injection, meaning it is delivered under the skin. Clinical trials are investigating various dosing approaches to determine the most effective and safest regimens for patients.
The dosing forms and regimens currently under study include:
- Adult Dosing Regimen 1
- Adult Dosing Regimen 2
- Adult Dosing Regimen 3
- Adolescent Dosing Regimen 1
- Adult Navenibart Dosing Regimen 1
- Adult Navenibart Dosing Regimen 2
- Adult Navenibart Dosing Regimen 3
- Adolescent Navenibart Dosing Regimen 1
- Cohort 1 - Single Dose
- Cohort 2 - Multiple Dose
- Cohort 3 - Multiple Dose
These investigational regimens are designed to evaluate different doses and frequencies of navenibart in both adult and adolescent populations to optimize treatment for Hereditary Angioedema. The studies include both single-dose and multiple-dose cohorts to assess the drug's pharmacokinetics and pharmacodynamics over time.
Side Effects
In a study (NCT05695248) evaluating navenibart in participants with hereditary angioedema (HAE), specific types of side effects were not detailed, and no placebo group was included for comparison. The study reported the number of participants who experienced any treatment-emergent adverse events (side effects that occurred or worsened during the study).
- Among 4 participants who received a single dose of navenibart, 4 participants experienced treatment-emergent adverse events.
- Among 13 participants who received multiple doses of navenibart, 9 participants experienced treatment-emergent adverse events.
- Among 12 participants who received multiple doses of navenibart (a different dosing regimen), 12 participants experienced treatment-emergent adverse events.
The study also tracked the development of anti-drug antibodies (ADAs), which are immune responses against the drug. These were observed in:
- 2 participants in the single-dose cohort.
- 3 participants in the multiple-dose cohort.
- 6 participants in the other multiple-dose cohort.
Further details on the specific nature or frequency of these adverse events are not available from this study data.
Clinical Trial Results
Results from a study (NCT05695248) investigated navenibart in participants with hereditary angioedema (HAE). The study included three cohorts: one receiving a single dose of navenibart (4 participants), and two receiving multiple doses (13 participants and 12 participants, respectively).
Impact on HAE Attack Rate and Frequency
- Participants experienced a significant reduction in their monthly HAE attack rate from baseline. The mean reduction was 84.1% in the single-dose cohort, 85.2% in the first multiple-dose cohort, and 88.3% in the second multiple-dose cohort.
- A notable proportion of participants became attack-free during the study:
- In the single-dose cohort, 1 out of 4 participants (25%) were HAE attack-free.
- In the first multiple-dose cohort, 6 out of 13 participants (approximately 46%) were HAE attack-free.
- In the second multiple-dose cohort, 7 out of 12 participants (approximately 58%) were HAE attack-free.
- The average number of HAE attacks requiring on-demand therapy varied across cohorts: 1.0 attack in the single-dose group, 6.4 attacks in the first multiple-dose group, and 3.5 attacks in the second multiple-dose group.
- The proportion of days without HAE attacks was high across all groups, averaging 0.988 (98.8%) for the single-dose cohort, 0.974 (97.4%) for the first multiple-dose cohort, and 0.984 (98.4%) for the second multiple-dose cohort.
Time to First Attack
- The median time until the first HAE attack after the initial dose was 109 days for the single-dose cohort.
- For the first multiple-dose cohort, the median time to the first HAE attack after the initial dose was 241 days. The median time to the first HAE attack after the last dose in this cohort was 159 days.
Biomarker Changes
Navenibart also led to reductions in plasma levels of cleaved high-molecular-weight kininogen (cHMWK), a biomarker associated with HAE activity. The mean percent change from baseline in cHMWK levels was:
- -60.7% in the single-dose cohort.
- -51.6% in the first multiple-dose cohort.
- -74.9% in the second multiple-dose cohort.
Currently Recruiting Trials
Navenibart is currently being investigated in clinical trials for hereditary angioedema (HAE), a rare genetic condition that causes recurrent episodes of severe swelling. If you or someone you know lives with HAE, you may be interested in learning about these ongoing studies. Two Phase 3 trials are currently recruiting participants to further evaluate navenibart.
One of the recruiting studies is "A Study of Navenibart in Participants With Hereditary Angioedema" (NCT06842823). This is a multicenter, randomized, double-blind, placebo-controlled clinical trial. It aims to evaluate the safety and efficacy of navenibart administered subcutaneously to adolescent and adult participants with type 1 or type 2 HAE. The trial is sponsored by Astria Therapeutics, Inc., and plans to enroll 145 participants. Participants may receive one of three adult navenibart dosing regimens or an adolescent navenibart dosing regimen.
Another opportunity to participate is in "A Long-Term Study of Navenibart in Participants With Hereditary Angioedema" (NCT07204938). This is a Phase 3 multicenter trial designed in two parts to assess the long-term safety and efficacy of navenibart. This study is specifically for adult and adolescent participants with HAE who have previously taken part in the STAR-0215-301 trial (NCT06842823; ALPHA-ORBIT). In Part 1 of this study, all participants will receive navenibart in a dose-controlled manner. This trial also aims to enroll 145 participants and is sponsored by Astria Therapeutics, Inc. Available dosages include three adult dosing regimens and one adolescent dosing regimen.
Where to Participate
Clinical trials for navenibart are being conducted across a wide geographic area, offering opportunities for participation in numerous locations. The studies are active at 21 sites spread across 20 cities in 14 states within the United States. These sites are carefully selected to ensure broad access for eligible individuals.
Top participating locations include:
- San Diego, California
- Little Rock, Arkansas
- Cincinnati, Ohio
- Scottsdale, Arizona
- Santa Monica, California
- Walnut Creek, California
- Centennial, Colorado
- Detroit, Michigan
- St Louis, Missouri
- Toledo, Ohio
For those considering participation, eligibility criteria specify that participants must be adolescents or adults. All genders are welcome to join these studies, but healthy volunteers are not eligible; participants must have a diagnosis of hereditary angioedema.
Development Timeline
The journey of navenibart in clinical development began on 2023-01-23 with its first clinical trial. Since then, the program has grown, with a total of 3 trials initiated and a cumulative enrollment target of 319 participants. All development efforts for navenibart have been driven by its sponsor, Astria Therapeutics, Inc., which has overseen every study to date.
Initially, the development pipeline for navenibart explored conditions such as IBS-C and hyperphosphatemia. However, the focus has since expanded and shifted to hereditary angioedema (HAE), reflecting a strategic progression in the drug's therapeutic targets. The trials have advanced through different phases, starting with a Phase 1/Phase 2 study and progressing to two ongoing Phase 3 trials, which are crucial steps toward potential regulatory approval.
The latest trial in the development timeline is projected to begin on 2025-10-03, indicating ongoing commitment to understanding navenibart's potential. This progression from early-stage research to advanced Phase 3 studies highlights the continuous effort to bring new treatment options to patients.