Chimerix, Inc., a biopharmaceutical company that licenses and potentiates existing antivirals using proprietary lipid technology, announced last month that their phase 3 trial of Brincidofovir (formerly CMX001) will include a secondary endpoint to determine the drug’s effectiveness in limiting the effects of HHV-6 infection among stem cell transplant patients. While the primary endpoint of the “SUPPRESS” trial is to determine efficacy in the treatment of CMV, this marks the largest multi-center prospective placebo-controlled trial to ever be conducted in HHV-6 infection. In addition to collecting fluid specimens, the group will also collect clinical data that will be used in analysis. One of the key pieces of clinical data that will be analyzed in conjunction with HHV-6 is the daily assessment of mental status, which has been shown to correlate inversely with HHV-6 viral load in a study by Danielle Zerr at University of Washington.
Brincidofovir, Chimerix’s lead product candidate, is an oral nucleotide analog that has shown broad-spectrum antiviral activity against all five families of double-stranded DNA (dsDNA) viruses that affect humans. Study CMX001-201, a 230-subject, randomized, placebo-controlled, double-blind, dose-escalation study, met the primary endpoint of reduction in CMV viremia and/or CMV disease for brincidofovir 100 mg twice weekly versus placebo (p=0.002). Based on these positive Phase 2 results, Chimerix recently initiated the Phase 3 SUPPRESS trial of brincidofovir 100 mg twice weekly for the prevention of CMV infection in HCT recipients. According to their website, the company believes this drug “has the potential to be the first broad-spectrum antiviral for the prevention and treatment of clinically significant infections and diseases caused by dsDNA viruses.”
Brincidofovir is a lipid-tagged version of the antiviral cidofovir (Vistide), and has previously shown enhanced antiviral efficacy against both HHV-6A and HHV-6B in vitro (Bonnafous 2012). Since there is no FDA approved drug specifically for HHV-6, an approval of brindocidofovir for HHV-6 would fill a significant unmet need.
Chimerix’s medical director Michelle Berrey recently addressed shareholders: “in addition to CMV, certainly, our most important endpoint in this trial, we will be looking at multiple other double-stranded DNA infections, specifically, those clinical endpoints and we do have a possibility of showing statistically significant reductions for many of these other viruses.” The proprietary lipid technology enhances bioavailability. The drug is also expected to work well for adenovirus, BK virus and herpes simplex viruses. The lipid technology was original developed by Karl Hostetler at University of California, San Diego and works by mimicking a naturally occurring phospholipid. The lipid tag also reduces systemic exposure and toxicity.
The results of the phase two trial of brindocidofovir/CMX-001 for CMV disease in stem cell transplant patients were published in the New England Journal of Medicine in September. The incidence of CMV disease was significantly lower (10% vs 25%) among patients who received 100 mg twice weekly. Diarrhea was the most common adverse event. Nephrotoxicity, the biggest concern with cidofovir treatment, was not observed. Bone marrow suppression, the most common side effect of valganciclovir and ganciclovir, was also not observed in the CMX001/brindocidofovir treated patients.
For more information on the SUPPRESS trial, visit the official trial page at ClinicalTrials.gov.