New AATD therapy may alleviate treatment burden for patients

A new investigational therapy for patients with alpha-1 antitrypsin deficiency (AATD) provided a longer duration of functional serum AAT than the duration that is usually seen for plasma-derived AAT, the standard-of-care for patients with AATD. 

“In patients with AATD, novel therapies that provide high levels of serum AAT with less frequent dosing are needed,” said Dr Brooks Kuhn (UC Davis School of Medicine, CA, USA) [1]. INBRX-101 is a recombinant, next-generation human AAT Fc-fusion protein, designed to have a longer half-life and higher exposure than human plasma-derived AAT, which is the current standard of care for these patients. This investigational agent was evaluated in an open-label, dose-escalation phase 1 trial (NCT03815396). Dr Kuhn presented the results of the ‘multiple ascending dose’ part of the study, in which 31 participants with AATD received 3 times 3-weekly infusions of INBRX-101 (40, 80, or 120 mg/kg). Safety was the primary endpoint of the study. 

“No patients had discontinued the study due to adverse events (AEs),” according to Dr Kuhn. The most common treatment-emergent AEs were fatigue (22.6%), increased blood pressure (12.9%), pruritus (9.7%), and urticaria (6.5%). “These were all grade 1 or 2 events that resolved in the same day with no to minimal supportive care,” commented Dr Kuhn. 

Furthermore, INBRX-101 showed a longer mean terminal elimination half-life (15.7–18.2 days) than that priorly observed for plasma-derived AAT (approximately 6 days). Also, measurable INBRX-101 exposure was reported across dose levels, up to 84 days after the third and final dose. Importantly, the 80 and 120 mg/kg INBRX-101 dose levels resulted in functional AAT levels that remained above the lower limit of normal during the 21-day dosing interval, and above the lower limit of normal after 28 days for the 120 mg/kg dose group after the third infusion. A phase 2 study is underway to further assess INBRX-101, 120 mg/kg, 3-weekly and 4-weekly, in patients with AATD (NCT05856331). 

1. Kuhn BT, et al. Recombinant Human Alpha-1 Antitrypsin (AAT) Protein INBRX-101 Demonstrates Potential to Achieve Lung Penetration and Normal Functional Serum AAT Levels in Patients With AAT Deficiency. C15, ATS International Conference 2023, 19–24 May, Washington DC, USA.

 

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Posted on 12 June 202313 June 2023