FDA Grants Fast Track Designation for Inhibrx Treatment of Alpha-1 Antitrypsin Deficiency
June 1, 2023
Rare Daily Staff
The U.S. Food and Drug Administration granted Fast Track designation to Inhibrx’ INBRX-101, an experimental therapy for the treatment of patients with emphysema due to alpha-1 antitrypsin deficiency.
Fast Track designation is granted by the FDA upon the request of the sponsor to facilitate the development and expedite the review of drugs intended to treat serious or life-threatening diseases. Depending upon the stage of the product’s development, the sponsor must also provide FDA with nonclinical or clinical data to demonstrate the drug’s potential to address unmet medical needs for such a disease or condition. Investigational drug products with Fast Track designation may benefit from early and frequent communication with the FDA, and are eligible for rolling submission and FDA review of its future marketing application.
Alpha-1 antitrypsin deficiency (AATD) is an inherited orphan disease affecting an estimated 100,000 patients in the United States. AATD is characterized by deficient levels of the AAT protein, which causes loss of lung tissue and function and decreased life expectancy. Augmentation therapy with plasma-derived AAT is the current standard of care but does not maintain patients in the normal AAT range, requires frequent and inconvenient once-weekly IV dosing, and relies on plasma collection practices that might not be sustainable.
INBRX-101 is an engineered recombinant human AAT-Fc fusion protein designed to safely achieve and maintain levels of AAT found in healthy individuals with the potential for a less frequent dosing interval compared to the weekly infusion interval of the currently available plasma-derived AAT therapies. In March 2022, the FDA granted orphan-drug designation for INBRX-101 for the treatment of AATD.
Data from the phase 1 multiple ascending dose study of INBRX-101 at 40, 80 and 120 mg/kg IV every three weeks showed the expected accumulation of functional AAT levels and the ability to achieve fully normal functional AAT levels in severely deficient AATD patients. Based on PK modeling, accumulation is expected to continue following subsequent doses and reach steady state after a total of approximately five to six consecutive doses, administered every three or four weeks.
Treatment was well tolerated with no severe or serious adverse events related to the study drug. Drug-related adverse events were predominantly mild and those few that were moderate in severity were all transient and reversible, with minimal or no symptomatic care. No safety-related or PK/PD-related signs of neutralizing anti-drug antibodies were observed.
The ElevAATe study is a registration-enabling trial for INBRX-101 initiated in April 2023 and is designed as a randomized, controlled, double-blind, head-to-head superiority study examining INBRX-101 against plasma-derived AAT. The primary endpoint is the mean change in the average functional AAT (fAAT) concentration as measured by anti-neutrophil elastase capacity (ANEC) from baseline to average serum trough fAAT concentration at steady state.
The initial read-out from the ElevAATe trial is expected to occur in late 2024.
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