avasopasem manganese IV

Proposed Indications

Radiotherapy (RT)-induced severe oral mucositis (SOM) in patients with head and neck cancer (HNC)

Clinical Overview

Avasopasem manganese is a selective dismutase mimetic designed to convert RT-induced bursts of superoxide to hydrogen peroxide in normal cells and cancer cells.

The randomized, double-blind, placebo-controlled, phase 3 ROMAN trial (NCT03689712) evaluated avasopasem manganese in 455 patients with HNC who were receiving intensity-modulated RT (IMRT) plus cisplatin chemotherapy. The study demonstrated a 16% relative reduction in the incidence of SOM (primary endpoint) through the end of the study treatment period (approximately 7 weeks) with avasopasem manganese compared to placebo (54% versus 64%, respectively; p=0.045) and a 56% relative reduction in SOM duration (median, 8 versus 18 days, respectively; p=0.002). In addition, after 1 year of follow-up, tumor outcomes and OS were comparable between the avasopasem manganese and placebo groups. Notably, according to a predefined exploratory analysis, after 1 year of post-treatment follow-up, significantly fewer patients in the avasopasem manganese group developed CKD, a known risk of cisplatin, compared to those in the placebo group (10% versus 20%, respectively; p=0.0043).

Avasopasem manganese 90 mg was infused IV over 60 minutes before each daily (Monday–Friday) RT fraction.

Place In Therapy

Chemotherapy and RT create reactive oxygen species within cells leading to cell damage and mucositis. Mucositis typically presents during the second or third week of RT and is characterized by erythema and ulceration of the mouth, but can occur throughout the entire GI tract. Approximately 70% of patients with HNC treated with cisplatin plus RT experience SOM (grade 3 or 4). Patients may experience pain and difficulty eating and swallowing warranting the need for enteral/parenteral nutrition, opioids for pain control, and interruption of cancer therapy, if severe. In addition, in immunocompromised patients, SOM may lead to infections, including bacteremia, resulting in hospitalization and increased mortality.

Symptomatic management of mucositis includes basic oral hygiene, dietary modifications, topical agents, and analgesics. Various types of mouthwash found in the literature are suggested to alleviate pain due to oral mucositis (OM). These include oral solutions of doxepin, hydrogen peroxide, normal saline, and baking soda, as well as “miracle” mouthwashes containing combinations of an antacid, diphenhydramine, viscous lidocaine, dexamethasone, nystatin, and/or an antibiotic. The Multinational Association of Supportive Care in Cancer (MASCC) recommends benzydamine mouthwash (anti-inflammatory; not available in the US), intraoral photobiomodulation (PBM) with low-level laser therapy, oral glutamine (off-label), and honey for the prevention of OM in patients with HNC receiving RT and chemotherapy. Topical morphine 0.2% mouthwash is also suggested to treat pain associated with OM. Several mucoadhesive products, considered devices by the FDA, are approved to manage OM symptoms, including Gelclair®, Mugard®, Mucotrol™, and Caphosol®; however, these agents have not been adequately evaluated in well-designed clinical trials.

If approved, avasopasem manganese will be the first systemic therapy for RT-induced SOM. Initial approval is expected for use in patients with HNC. Dusquetide, an innate defense regulator administered via a 4-minute IV infusion every 2 weeks, is in phase 3 trials for OM in patients with HNC receiving RT plus chemotherapy.

The financial forecast for avasopasem manganese is not currently available.