ALTU-237 — Reloxaliase (oxalate decarboxylase)

About this submission

IND for an oral recombinant enzyme treating enteric hyperoxaluria. Instructive for sponsors developing oral biologics — non-systemic delivery, GI-tract pharmacology, and enzyme stability data are all atypical for Module 3.

Complete INDs almost never see daylight — and this is the deepest one in the archive: sixteen years and roughly 140 FDA submissions for a non-absorbed oral enzyme that degrades oxalate in the gut, sparing the kidneys from the stones and damage oxalate overload causes. Begun at Altus Pharmaceuticals as ALTU-237 and carried forward by Allena, the file runs from a 2006 pre-IND meeting through two Phase 3 trials (URIROX-1 and URIROX-2). If you're learning how a program actually talks to the FDA over its lifetime, it's an unusually complete worked example of surrogate-endpoint strategy, accelerated-approval negotiation, and multi-generation CMC scale-up.

What the FDA dialogue reveals

• A surrogate-endpoint negotiation, start to finish. The whole program turned on one question: can lowering urinary oxalate — a lab value — support approval without first proving fewer kidney stones? The FDA said no at End-of-Phase-2 (2017) and again in 2018, then agreed an accelerated-approval path in Dec 2018 — but only with a model linking the surrogate to actual stone outcomes. About three years from ask to alignment, all in the record.
• The FDA holds a position — consistently. Across years it repeats and cites its own prior letters. Read in sequence, the minutes are a tutorial in how the agency reasons and where it won't move.
• A designation denied, candidly. A Breakthrough Therapy request was rejected even though the FDA agreed the disease was serious — the supporting data (seven patients, several on dialysis, which itself clears oxalate) were judged too thin. A clear-eyed lesson in the evidentiary bar for designations.
• CMC as a marathon. The manufacturing process was rebuilt across four generations (FFDB → Lonza → intermediate → full scale) — a real template for managing comparability through scale-up.

Best studied for

Surrogate-endpoint and accelerated-approval strategy in nephrology / metabolic disease · Type A/B/C and End-of-Phase-2 meeting preparation · CMC comparability across manufacturing scale-up · long-horizon IND lifecycle management.

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