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Title: Maribavir: 1263W94, Benzimidavir, GW 1263, GW 1263W94, VP41263.
Journal: Drugs R D; 2007; 8(3):188-92. PubMed ID: 17472414.
Abstract:
Maribavir is a novel benzimidazole riboside compound that is currently in clinical development with ViroPharma for the prevention of cytomegalovirus (CMV) infections in transplant patients. Maribavir is thought to inhibit viral DNA assembly and inhibit egress of viral capsids from infected cell nuclei. This mechanism is different to other available CMV treatments that inhibit CMV DNA polymerase. Maribavir, originally developed by GlaxoSmithKline, was licensed to ViroPharma in August 2003. Glaxo was conducting phase I/II clinical studies in the EU and the US in 2001, but discontinued development because the company felt that there was no longer a significant clinical need for maribavir as advances in the treatment of HIV have lead to improved immune systems in patients, resulting in a reduction in the incidence of CMV and CMV retinitis. In August 2003, ViroPharma acquired exclusive worldwide rights (excluding Japan) to develop and commercialise maribavir for the prevention and treatment of CMV infections related to transplant and congenital transmission and in patients with HIV infection. ViroPharma paid GlaxoSmithKline a $US3.5 million upfront licensing fee and will pay additional milestones based on defined clinical development and regulatory events. The company will also pay royalties on product sales in the US and the rest of the world, excluding Japan.A phase III study with maribavir as a prophylactic agent in patients undergoing allogeneic stem cell transplant who are CMV seropositive has been initiated and another phase III trial in solid organ transplant patients is planned. The stem cell transplant trial will take approximately 18 months to complete enrolment and the solid organ transplant trial, which won't be as large as the stem cell transplant trial, will be completed within this time-frame also. ViroPharma hopes to file an NDA for maribavir in 2009. Maribavir was granted fast-track status by the US FDA in February 2006 for the prevention of CMV infection in allogeneic bone marrow and solid organ transplant patients. Maribavir has received orphan drug status in the US for the prevention of CMV viraemia and disease in at-risk populations. ViroPharma has conducted a dose-ranging phase II clinical study designed to evaluate the antiviral activity, safety and pharmacokinetic profile of maribavir for the prevention of CMV infection in patients who have undergone allogeneic stem cell transplantation. The randomised, double-blind, placebo-controlled, dose-ranging study was conducted at 13 transplant centres across the US. Patients (n = 111) were randomised 3 : 1 to receive maribavir in three ascending dose groups (100mg bid, 400mg qd, 400mg bid) or placebo for up to 12 weeks. Enrolment in the phase II trial was completed in November 2005. Preliminary results have been reported. In February 2004, ViroPharma announced the initiation of a clinical programme to develop maribavir for prevention of CMV infection in transplant patients. A phase I drug-drug interaction and safety study in healthy volunteers, designed to evaluate the potential for maribavir to affect the blood levels of various other drugs that are metabolised by the liver, was conducted in the US. Results of this study were reported in March 2005. A second phase I study was initiated in March 2004 to evaluate the pharmacokinetic profile of a single 400mg dose of maribavir in patients with varying levels of renal functional impairment, compared with subjects with normal renal function. Maribavir has been tested in several phase I studies by GlaxoSmithKline, in which the drug demonstrated antiviral activity, oral bioavailability and an acceptable safety and tolerability profile.The patents covering maribavir held by GlaxoSmithKline expire in 2015.

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