In the study of resistant/refractory CMV, among 31 subjects receiving maribavir, 26 (84 percent) achieved BQL during therapy, 4 subjects failed to achieve BQL while on therapy, and 1 subject had withdrawn for non-virologic reasons prior to achieving BQL. Eleven of the 26 subjects who achieved BQL subsequently experienced virologic breakthrough while on treatment.
As a reminder, these studies are ongoing, so different subjects have been followed for different periods of time. Also all subjects will continue to be followed after the end of treatment to monitor for the return of detectable plasma CMV DNA when off antiviral therapy (which is not uncommon following the use of currently available anti-CMV therapies).
To date, in both ongoing studies maribavir appears to demonstrate a favorable safety and tolerability profile. An independent data monitoring committee is monitoring the studies, and to date it has convened once to review data from the asymptomatic study with no findings of concern. Adverse events seen in these studies appear generally consistent with those expected in transplant recipient populations and what has been observed in more than 1,000 patients who have received maribavir in previous clinical studies.
"The results we've seen to date are very positive and encouraging," stated
, ViroPharma's president and chief executive officer. "We appear to have very good response – about 90 percent - in treating asymptomatic CMV viremia, which is what one would expect for a potent anti-CMV treatment. Not surprisingly, the resistant/refractory patients are more complicated, and we are seeing nearly 85 percent of patients attaining undetectable viral levels and a sustained antiviral response through the end of treatment in roughly half of the enrolled subjects, which is impressive given the lack of treatment options and high unmet need in these patients. There remain a number of elements of the studies which we will not be able to fully analyze until after study completion (including effects of maribavir dose, pre-treatment viral load, emergence of viral resistance and various patient factors). These data are consistent with what we had hoped to see and had seen in previous clinical experiences with maribavir as a treatment for CMV. We are now fully committed to this development program and intend to focus on accelerating the completion of both studies. As a result, moving forward, we intend to limit the number of future interim data disclosures."
Maribavir, a member of a new class of drugs called benzimidazole ribosides, is a potent and selective, orally bioavailable antiviral drug with a unique mechanism of action against cytomegalovirus and a favorable clinical safety profile. Unlike currently available anti-CMV agents that inhibit CMV DNA polymerase, maribavir inhibits viral DNA assembly and inhibits egress of viral capsids from the nucleus of infected cells. Maribavir is active in vitro against strains of CMV that are resistant to commonly used anti-CMV drugs. Maribavir does not affect the maturation of viral DNA or affect the viral DNA polymerase. The previous focus of clinical development of maribavir as an anti-CMV agent was on the prevention of CMV disease in transplant patients. Results from Phase 3 studies indicated that maribavir at a dose of 100mg BID failed to meet its efficacy endpoints. However, maribavir has demonstrated a favorable safety and tolerability profile; across all clinical studies to date, the most notable adverse event associated with maribavir was taste disturbance. While Phase 3 studies of CMV prophylaxis at the 100mg BID dose did not show sufficient activity to prevent CMV disease, limited data from cases in which open-label maribavir was used as CMV treatment suggest that higher doses may provide clinical activity and clinical studies are ongoing. The U.S. Food and Drug Administration (FDA) and the European Commission have granted orphan drug designation to maribavir for treatment of clinically significant cytomegalovirus viremia and disease in at-risk patients, and the prevention and treatment of cytomegalovirus disease in patients with impaired cell mediated immunity, respectively.