On April 26, 2023 Inhibrx, Inc. (Nasdaq: INBX), a clinical-stage biopharmaceutical company dedicated to the development of therapeutics for oncology and rare diseases, reported that it has initiated a registration-enabling trial for INBRX-101, an optimized recombinant human AAT-Fc fusion protein, for treatment of patients with emphysema due to alpha-1 antitrypsin deficiency (AATD) (Press release, Inhibrx, APR 26, 2023, View Source [SID1234630525]). Additionally, the Company announced that the U.S. Food and Drug Administration (FDA) has lifted the partial clinical hold on studies evaluating its death-receptor 5 (DR5) agonist, INBRX-109.
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INBRX-101
The ElevAATe trial is designed as a randomized, controlled, double-blind, head-to-head superiority study examining INBRX-101 against plasma-derived AAT (pdAAT). The study design is as follows: 36 patients dosed every three weeks with INBRX-101 at 120 mg/kg, 36 patients dosed every four weeks with INBRX-101 at 120 mg/kg, and 18 patients dosed weekly with pdAAT at the FDA-approved dose. The treatment period is 32 weeks and will be conducted at approximately 35 sites in the United States, Australia and New Zealand.
The primary endpoint of the trial 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 (Ctrough,ss). Secondary endpoints are a comparison of the mean change in fAAT concentration from baseline to fAAT average concentration at steady state (Cavg,ss), and the percentage of days with fAAT above the lower limit of the normal range during steady-state dosing. A bronchoscopy sub-study of approximately 30 patients will also run at designated sites.
The initial read-out from the ElevAATe trial is expected to occur in late 2024.
INBRX-109
In March 2023, the Company announced the pause in patient enrollment for the INBRX-109 (DR5 agonist) trials as a result of the pre-defined stopping rules built into the Phase 2 protocol. This did not impact active patients who were already on treatment and remained on the trial. With data from over 200 patients dosed with INBRX-109 to date, the Company was able to more precisely identify elderly individuals with fatty liver disease as the at-risk population for severe liver toxicity. As a result, the Company amended its protocol to include the Hepatic Steatosis Index (HSI) as part of the screening criteria.
Exhibit 99.1
In April 2023, the FDA lifted the partial clinical hold. Patient enrollment is expected to resume next month. Phase 1 combination cohorts are expected to begin reading out by the end of 2023 and data from the registration-enabling trial in unresectable or metastatic conventional chondrosarcoma is expected during the second half of 2024.
About INBRX-101 and AATD
INBRX-101 is a precisely engineered recombinant human AAT-Fc fusion protein designed to safely achieve and maintain levels of alpha-1 antitrypsin (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.
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.
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.
In March 2022, the FDA granted orphan-drug designation for INBRX-101 for the treatment of AATD.
About INBRX-109 and Chondrosarcoma
INBRX-109 is a precision-engineered, tetravalent death receptor 5 (DR5) agonist antibody designed to exploit the tumor-biased cell death induced by DR5 activation.
Chondrosarcoma is an orphan bone cancer with approximately 2,800 new patients diagnosed annually in the United States and the EU. There are currently no therapeutics approved for the treatment of chondrosarcoma.
In 2021, the FDA granted Fast Track designation to INBRX-109 for the treatment of patients with unresectable or metastatic conventional chondrosarcoma and orphan-drug designation to INBRX-109 for chondrosarcoma in the United States.
In June 2021, Inhibrx initiated a randomized, blinded, placebo-controlled, potential registration-enabling Phase 2 trial of INBRX-109 in conventional chondrosarcoma. This trial, in addition to the additional Phase 1 cohorts examining INBRX-109 in combination with certain chemotherapies, are currently ongoing.