Arrowhead Pharmaceuticals announced the U.S. Food and Drug Administration (FDA) has granted Fast Track designation to ARO-AAT, the company’s second generation subcutaneously administered RNA interference (RNAi) therapeutic being developed as a treatment for a rare genetic liver disease associated with alpha-1 antitrypsin deficiency (AATD). Arrowhead is in final preparations to initiate SEQUOIA (AROAAT2001), a potentially pivotal Phase 2/3 clinical study in the U.S. and Europe, and AROAAT2002, a Phase 2 open-label clinical study in Europe.
“With no currently approved agents to treat AATD-associated liver disease, alpha-1 patients and their physicians have an urgent need for new therapeutic options,” said Bruce Given, M.D., Arrowhead’s chief operating officer and head of R&D. “We view this FDA Fast Track designation as continued support that ARO-AAT has the potential to address this unmet need. Importantly, Fast Track designation provides a number of important advantages that could expedite the development and review of ARO-AAT.”
Fast Track is a process designed to facilitate the development and expedite the review of drugs to treat serious conditions and fill an unmet medical need. The purpose is to get important new drugs to the patient earlier.
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- A drug that receives fast track designation is eligible for some or all of the following:
- More frequent meetings with FDA to discuss the drug's development plan and ensure collection of appropriate data needed to support drug approval
- More frequent written communication from FDA about such things as the design of the proposed clinical trials and use of biomarkers
- Eligibility for accelerated approval and priority review, if relevant criteria are met
Rolling Review, enabling a drug company to submit completed sections of its New Drug Application (NDA) for review by FDA, rather than waiting until every section of the NDA is completed before the entire application can be reviewed. NDA review usually does not begin until the drug company has submitted the entire application to the FDA.
SEQUOIA (NCT03945292) is a placebo-controlled, adaptive design Phase 2/3 study to evaluate the safety, efficacy, and tolerability of ARO-AAT administered subcutaneously to 120 patients with AATD-associated liver disease. Doses will be administered on day 1, 29, and approximately every 12 weeks thereafter. The four-arm placebo-controlled Part A component of the study will feed seamlessly into a two-arm placebo-controlled Part B component. The primary objective for Part A is to select a single dose level for use in Part B of the study based on a combined evaluation of safety and pharmacodynamic dose response in each Part A cohort using change from baseline in soluble liver mutant AAT (Z-AAT), insoluble liver Z-AAT, and serum AAT levels as pharmacodynamic metrics. The primary objective for Part B is to evaluate efficacy, as assessed by the proportion of ARO-AAT treated patients relative to placebo achieving a 2-point improvement in a histologic grading scale of AATD-associated liver disease, and no worsening of liver fibrosis on end of study biopsy.
AROAAT2002 (NCT03946449) is a pilot open-label, multi-dose Phase 2 study to assess changes in a histologic grading scale in response to ARO-AAT administration in up to 12 patients with AATD-associated liver disease. Doses will be administered on day 1, 29, and approximately every 12 weeks thereafter. The histologic grading score will be assessed at weeks 24 and 72 for cohort 1 and weeks 48 and 96 for cohort 2. Multiple secondary and exploratory objectives will also be assessed throughout the study.