FDA Lifts Hold on IND for Phase 3 Trial of Ataxia Agent EryDex

Dirk Thye, MD

According to a recent announcement, the FDA has lifted its clinical hold on the investigational new drug application (IND) for Quince Therapeutics agent EryDex, a unique autologous drug/device combination agent in development for patients with ataxia-telangiectasia (A-T). The company will now proceed with its phase 3 NEAT trial assessing the safety and efficacy of the therapeutic in A-T, with a potential new drug application submission at the end of 2025, pending positive results.¹

EryDex is an automated outpatient bedside technology to ex-vivo encapsulate dexamethasone sodium phosphate (DSP) into patient’s red blood cells, which are then re-infused, allowing for the circulation of controlled, slow release, low doses of dexamethasone over the subsequent several weeks following treatment. To date, the therapy has gained orphan drug designation for the treatment of A-T both from the FDA and European Medicines Agency. EryDex is part of a larger technology platform, the EryDex System, that is capable of expansion to other drugs or biologics, including enzyme replacement therapy.

"We are pleased with the FDA’s decision to lift the partial clinical hold related to EryDel’s lead asset, EryDex. We look forward to completing the clinical and regulatory activities necessary to advance EryDex into the Phase 3 NEAT study – with patient enrollment beginning as soon as the second quarter of 2024,” Dirk Thye, MD, chief executive officer, Quince, said in a statement.^{1 "}Notably, this pivotal trial will be conducted under a Special Protocol Assessment (SPA) that has already been reviewed with the FDA, which should allow for the submission of a New Drug Application (NDA) following completion of this single study, assuming positive results."

NEAT, a phase 3 study, is double-blinded, placebo-controlled in design, and is expected to include 86 patients with A-T aged 6 to 9 years old, with up to an additional 20 patients aged 10 years or older to potentially expand the label. The primary end point, an evaluation of patient’s function, will be based on changes on a rescored modified International Cooperative Ataxia Rating Scale (RmICARS). Secondary end points include measures of Clinical Global Impression scores for severity and change, as well as EuroQol quality of life scoring.

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In late July, Quince announced the acquisition of EryDel SpA, a privately-held, late-stage biotech company, and its lead assess EryDex. In the company’s latest update, they noted the acquisition is expected to close in the fourth quarter of 2023, and is subject to certain regulatory approvals, including the foreign direct investment screening clearance in Italy, and other closing conditions.²

The safety and efficacy of EryDex was documented in the phase 3 ATTeST study (NCT02770807), the largest such study of patients with A-T. Conducted between March 2017 and March 2020, 175 patients were enrolled and 164 were randomized; 132 (80.5%) completed the 24 weeks of the primary efficacy period. All told, the full analysis set (n = 164) showed favorable outcomes on the primary end point of mICARS and RmICARS in the treated groups compared with placebo, but did not reach statistical significance.

The per-protocol analysis (n = 107) showed slower rate of neurologic deterioration for both the 5-10 mg dose or 14-22 mg dosed groups compared with placebo (low dose: mICARS: P = .004; RmICARS = P = .003; high dose: mICARS: P = .019; RmICARS = P = .036). The a priori age 6-9 year olds’ intent-to-treat analysis (n = 89) showed a statistically significant favorable outcome for high dose vs placebo (mICARS: P = .019; RmICARS: P = 0.28). Treatment-emergent adverse events occurred in 73%, 82%, and 73% of patients in the low dose, high dose, and placebo groups, respectively.³

REFERENCES
1. US FDA partial clinical hold lifted on IND for EryDel’s lead phase 3 asset EryDex for the treatment of ataxia-telangiectasia. News release. Quince Therapeutics. September 28, 2023. Accessed October 4, 2023. https://ir.quincetx.com/news-releases/news-release-details/us-fda-partial-clinical-hold-lifted-ind-erydels-lead-phase-3
2. Quince Therapeutics to acquire EryDel SpA and its phase 3 asset targeting ataxia-telangiectasia with no currently approved treatments and estimated $1+ billion peak sales opportunity. News release. Quince Therapeutics. July 24, 2023. Accessed October 4, 2023. https://www.sec.gov/Archives/edgar/data/1662774/000119312523191839/d542769dex992.htm
3. Zielen S, Whitehouse W, Magnani M, Perlman SL, Leuzzi V, Lederman HM. The pivotal multi-center, randomized, double-blind, placebo-controlled trial of intra-Erythrocyte Dexamethasone Sodium Phosphate (ATTeST) on the neurological motor function of people with Ataxia Telangiectasia. Presented at: 2022 AAN Annual Meeting. Abstract 52072