Report on Heme Arginate (DB17310): A Comprehensive Monograph

Executive Summary

Heme arginate (DrugBank ID: DB17310) is a biotech therapeutic agent representing a significant advancement in the management of acute hepatic porphyrias. It is a chemically stabilized complex of heme and the amino acid L-arginine, a formulation engineered to overcome the profound instability and associated adverse effects of its predecessor, hematin. The primary and approved indication for heme arginate is the treatment of acute, life-threatening attacks of hepatic porphyria, including acute intermittent porphyria (AIP), variegate porphyria (VP), and hereditary coproporphyria (HCP). Its mechanism of action in this context is a classic example of metabolic feedback inhibition; by replenishing the deficient hepatic heme pool, it downregulates the activity of δ-aminolevulinic acid synthase 1 (ALAS1), the rate-limiting enzyme in heme biosynthesis. This action rapidly suppresses the overproduction of neurotoxic heme precursors—δ-aminolevulinic acid (ALA) and porphobilinogen (PBG)—which are the direct cause of the severe neurovisceral symptoms characteristic of an acute attack.

Beyond its established role in porphyria, heme arginate possesses a distinct and compelling secondary pharmacology centered on its ability to potently induce the cytoprotective enzyme heme oxygenase-1 (HO-1). The catabolism of heme by HO-1 generates antioxidant, anti-inflammatory, and anti-apoptotic molecules, a mechanism that has positioned heme arginate as a promising candidate for therapeutic repurposing in a range of conditions characterized by cellular stress and ischemia-reperfusion injury (IRI). This has led to significant investigational research, including clinical trials exploring its potential to mitigate delayed graft function in kidney transplantation and acute kidney injury following cardiac surgery.