The US Food and Drug Administration (FDA) has granted Fast Track Designation to INBRX-101, an engineered recombinant human alpha-1 antitrypsin (AAT)-Fc fusion protein being developed by Inhibrx for the treatment of patients with emphysema due to alpha-1 antitrypsin deficiency (AATD).
INBRX-101 therapy aims to safely achieve and maintain the levels of the AAT protein found in healthy individuals, which was supported by data from the phase 1 multiple ascending dose study.
The study has demonstrated that INBRX-101 at 40, 80, and 120 mg/kg, administered intravenously every 3 weeks, led to the expected accumulation of functional AAT levels and showed the ability to achieve fully normal functional AAT levels in patients with severe AATD.
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Moreover, pharmacokinetic modeling suggests that accumulation might continue following subsequent doses. The steady state is expected to be reached after a total of approximately 5 to 6 consecutive doses, administered every 3 or 4 weeks.
Read more about AATD experimental therapies
Treatment with INBRX-101 was well tolerated, with no severe or serious adverse events being reported. Most drug-related adverse events were mild. Also, the moderate drug-related adverse events were all transient and reversible, with minimal or no symptomatic care.
Furthermore, the investigators did not observe safety-related or pharmacokinetic/pharmacodynamic-related signs of neutralizing antidrug antibodies.
INBRX-101 is being evaluated in comparison with plasma-derived AAT in a randomized, controlled, double-blind, head-to-head superiority study called ElevAATe (NCT05856331).
The primary endpoint is the mean change in the average functional AAT concentration as measured by antineutrophil elastase capacity from baseline to average serum trough fAAT concentration at steady state.
The initial data from ElevAATe is expected to be revealed in late 2024.
INBRX-101, which received FDA’s Orphan Drug Designation in March 2022, offers the advantage of potentially requiring a less frequent dosing interval compared with the weekly infusion interval of the currently available plasma-derived AAT therapies.
Reference
Inhibrx granted fast track designation for INBRX-101 for the treatment of alpha-1 antitrypsin deficiency. News release. Inhibrx, Inc.; May 30, 2023.
