VI-0609: An Ethanol-Free Carmustine Formulation for Lymphoma Conditioning Therapy – A Comprehensive Review

1. Executive Summary

VI-0609 is an investigational, innovative, ethanol-free formulation of the alkylating agent carmustine, developed by VIVUS LLC. Its primary objective is to address the significant infusion-related toxicities associated with the conventional ethanol-containing carmustine formulation (BiCNU), particularly when used in high-dose chemotherapy regimens prior to autologous hematopoietic cell transplantation (AHCT) for patients with lymphoma. These toxicities, often attributed to the ethanol solvent, include facial pain, nausea, vomiting, and local irritation, contributing to patient burden and potentially limiting the rate of drug administration.

Currently, VI-0609 is undergoing a multicenter, randomized Phase 2 clinical trial (NCT06915246) where it is being compared directly to BiCNU within the standard BEAM (Carmustine, Etoposide, Cytarabine, Melphalan) conditioning regimen for adult patients with relapsed or refractory Hodgkin or Non-Hodgkin lymphoma. The trial's primary endpoints focus on evaluating infusion-related toxicities within 24 hours post-infusion and unacceptable toxicities through Day 30 post-AHCT. Early reports suggest VI-0609 may utilize propylene glycol as an alternative solvent.

The anticipated benefits of VI-0609 include an improved safety and tolerability profile concerning infusion reactions, potentially allowing for shorter infusion times and thereby reducing patient discomfort and healthcare resource utilization. While VI-0609 aims to mitigate solvent-related adverse events, the intrinsic pharmacological properties and systemic toxicities of carmustine, such as myelosuppression and pulmonary toxicity, are expected to remain.