A Comprehensive Monograph on 2-(1-Hexyloxyethyl)-2-devinyl pyropheophorbide-a (HPPH): A Second-Generation Photosensitizer for Photodynamic Therapy

Executive Summary

2-(1-Hexyloxyethyl)-2-devinyl pyropheophorbide-a, commonly known by the abbreviation HPPH and the developmental name Photochlor, is an investigational small molecule belonging to the chlorin class of photosensitizers.[1] It has been developed as a second-generation agent for photodynamic therapy (PDT), a non-invasive therapeutic modality for cancer treatment. The central value proposition of HPPH lies in its significantly improved safety and tolerability profile compared to the first-generation, FDA-approved photosensitizer, porfimer sodium (Photofrin®). Specifically, HPPH is characterized by mild and rapidly resolving cutaneous photosensitivity, a side effect that severely limits the clinical utility of its predecessors.[3]

The mechanism of action of HPPH is consistent with the principles of PDT. Following intravenous administration, the molecule selectively accumulates in neoplastic tissues. Subsequent irradiation of the tumor with light at a specific wavelength—approximately 665 nm—excites the drug, leading to a photochemical reaction with molecular oxygen. This process generates highly cytotoxic singlet oxygen (1O2​), which induces oxidative damage, vascular shutdown, and direct tumor cell death via necrosis and apoptosis.[6] The molecule's photophysical properties are a key advantage; its long activation wavelength allows for deeper light penetration into tissue, enabling the treatment of larger and more deep-seated tumors than is possible with first-generation agents.[3]