FDA grants priority review to novel flu antiviral

Genentech announced that the FDA has accepted a new drug application and granted priority review for the company’s single-dose, oral influenza treatment baloxavir marboxil.

The investigational medication is designed to inhibit the cap-dependent endonuclease protein crucial for influenza virus replication, including in oseltamivir-resistant and avian strains, according to a news release. It is intended for patients aged 12 years and older with acute, uncomplicated influenza.

Genentech said the FDA is expected to make a decision on the approval of baloxavir marboxil by Dec. 24. If approved, it would be the first influenza treatment with a novel mechanism of action in almost 20 years, the release said.

“The severity of the recent flu season underscores the need for new options beyond currently available treatments,” Sandra Horning, MD, chief medical officer and head of global product development at Genentech, said in the release. “Baloxavir marboxil has been shown in clinical trials to decrease the duration of symptoms with one dose and demonstrated a significant reduction in viral shedding in just 1 day. We look forward to working with the FDA during the review process.”

The new drug application (NDA) is based on phase 3 data from CAPSTONE-1, a multicenter, randomized, double blind trial conducted in the United States and Japan. The trial compared the safety and efficacy of baloxavir marboxil with placebo or 75 mg of oseltamivir twice a day for 5 days in 1,436 patients aged 12 to 64 years with uncomplicated influenza.

According to results presented at IDWeek, it was associated with a shorter duration of influenza symptoms compared with placebo — 53.7 hours vs. 80.2 hours (P < .0001) — and reduced the time to resolution of fever, which took 24.5 hours vs. 42 hours for placebo. There was no significant difference in the duration of symptoms or fever between the baloxavir marboxil and oseltamivir groups.

In other results, the median time to the cessation of viral shedding was 24 hours in patients who received baloxavir marboxil, 72 hours in patients who received oseltamivir (P < .0001) and 96 hours in those who received placebo (P < .0001). In addition, baloxavir marboxil significantly reduced viral titers in the nose and throat from 24 hours through 120 hours compared with placebo, and at 24 hours and 72 hours compared with oseltamivir, the release said.

In a safety analysis, baloxavir marboxil was well-tolerated and had a lower overall incidence of treatment-emergent adverse events (20.7%) compared with oseltamivir (24.8%) and placebo (24.6%). The most common adverse events reported by patients in the baloxavir marboxil group were diarrhea (3%), bronchitis (2.6%), nausea (1.3%) and sinusitis (1.1%).

The NDA is also supported by data from a phase 2, placebo-controlled study in otherwise healthy patients with influenza, according to the release. Baloxavir marboxil will continue to be assessed during a phase 3 development program. Genentech said findings from the CAPSTONE-2 trial, which includes adult and pediatric patients at high risk for influenza complications, will be announced at a later date.

The Roche Group, which includes Genentech, is developing baloxavir marboxil globally under an agreement with Shionogi & Co., Ltd., which discovered the treatment. Roche holds rights to baloxavir marboxil worldwide, except for in Japan and Taiwan. In these countries, rights to the antiviral are held exclusively by Shionogi.

In February, the Japanese Ministry of Health, Labor and Welfare approved balaxovir marboxil for adult and pediatric patients with influenza types A and B. It is sold under the brand name Xofluza.

References:

Genentech. FDA Grants Priority Review to Genentech’s Baloxavir Marboxil for the Treatment of Influenza. https://www.gene.com/media/press-releases/14732/2018-06-25/fda-grants-priority-review-to-genentechs. Accessed June 26, 2018.

Portsmouth S, et al. Abstract LB-2 Presented at: IDWeek; Oct. 4-8, 2017; San Diego.

Disclosures: Horning is an employee of Genentech.