-- First-Line Use of Brincidofovir for CMV May Preserve Subsequent Therapeutic Options --
-- Data Presented at 2014 Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC) --
DURHAM, N.C., Sept. 8, 2014 (GLOBE NEWSWIRE) -- Chimerix, Inc. (Nasdaq:CMRX), a biopharmaceutical company developing novel, oral antivirals in areas of high unmet medical need, announced new data today that suggests a potentially favorable resistance profile for brincidofovir for the treatment of life-threatening adenovirus and the prevention and treatment of cytomegalovirus (CMV). Results of the in vitro (cell culture) and Phase 2 studies were presented at the 54th Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC) in Washington, D.C.
"Drug resistance can be a significant issue in the treatment of viral diseases, particularly in immunocompromised patients," said M. Michelle Berrey, M.D., M.P.H., President and Chief Executive Officer of Chimerix. "We are encouraged by the high barrier to resistance seen in early studies for brincidofovir in adenovirus and we look forward to gathering more data through our Phase 3 AdVise study, which is currently enrolling patients. Additionally, the data for CMV suggest that first-line use of brincidofovir preserves the option for subsequent therapies, clearly a desirable feature in any first-line CMV prevention."
Resistance Profile of Adenovirus Exposed to Brincidofovir In Vitro and In Vivo (Abstract V-1302)
In an in vitro study of human adenovirus, brincidofovir and cidofovir were evaluated in increasing concentrations for antiviral activity. The development of brincidofovir-resistant adenovirus required two mutations to decrease brincidofovir's activity by four-to-eight-fold. These mutations required more than five months of exposure to brincidofovir in cell culture before they emerged.
In an exploratory Phase 2 study, 48 allogeneic hematopoietic cell transplant recipients with asymptomatic adenovirus levels ≥ 100 c/mL were randomized to placebo, brincidofovir once weekly, or brincidofovir twice weekly for 12 weeks. At 12 weeks, only one subject was identified with adenovirus containing one of the mutations detected in vitro. The mutation observed may have been present prior to brincidofovir therapy since previous use of antivirals, including cidofovir, was not excluded.
These data provide preliminary evidence that brincidofovir resistance to adenovirus may be slow to emerge in humans.
Combination Activity and Emerging Resistance Profile of Brincidofovir in CMV Prevention and Treatment (Abstract V-677)
The combination activity and resistance profile of brincidofovir for CMV were evaluated in vitro and in two Phase 2 clinical trials. Study 201 enrolled 171 antiviral-naïve patients with CMV and Study 350 enrolled 210 heavily pre-treated patients with life-threatening DNA viral infections, including 107 patients with CMV as the primary viral infection.
In vitro, brincidofovir selected a unique mutation in the CMV DNA polymerase that led to slower virus replication and resistance to brincidofovir or cidofovir, but not cross-resistance to ganciclovir or foscarnet.
In Study 201, no resistance-associated mutations were detected, suggesting first-line use of brincidofovir may not cause cross-resistance. In Study 350, 59 patients were evaluable and had baseline sequence data available. Two evaluable patients had baseline CMV DNA polymerase mutations associated with resistance to ganciclovir, cidofovir, or brincidofovir. These two patients did not achieve viral levels below measurable quantity (less than 200 virus copies per mL in plasma) at the last time on therapy. However, of the remaining evaluable patients with baseline sequence available, including many who were resistant to ganciclovir with common mutations, 25 (44%) achieved viral levels below 200 copies per mL and 36 (63%) had at least a 0.5 log10 decrease in viral load.
The results suggest that while the prior use of CMV antivirals leading to resistance-associated mutations can reduce brincidofovir activity, first-line use of brincidofovir for CMV prevention may preserve subsequent therapeutic options.
About Brincidofovir (CMX001)
Chimerix's lead product candidate, brincidofovir, is an oral nucleotide analog that has shown broad-spectrum in vitro antiviral activity against all five families of DNA viruses that affect humans, including viruses in the herpes virus family and adenovirus. Brincidofovir has shown no evidence of kidney or bone marrow toxicity in nearly 900 patients treated to date. Building on the positive Phase 2 results in cytomegalovirus (CMV) prevention, Chimerix initiated the Phase 3 SUPPRESS trial in 2013. If positive, data from SUPPRESS will support Chimerix's initial regulatory submission for brincidofovir for the prevention of CMV infection in adult hematopoietic cell transplant (HCT) recipients. Chimerix recently initiated AdVise, a Phase 3 trial in adenovirus, which is an often-fatal viral infection with no approved treatment; enrollment is ongoing for the pilot portion of the trial. Chimerix is also working with the Biomedical Advanced Research and Development Authority (BARDA) to develop brincidofovir as a medical countermeasure against smallpox. Brincidofovir has received Fast Track designation from the FDA for CMV, adenovirus, and smallpox.
Adenovirus causes upper respiratory infections, including the common cold, in individuals with intact immune systems; however, it is often rapidly fatal in patients with compromised immune responses. Adenovirus is most common during the post-transplant period when the immune system is weak. No therapies are approved for the treatment of adenovirus.
About Cytomegalovirus (CMV)
CMV is a member of the herpes virus family and remains the most common cause of fatal infections in hematopoietic cell transplant (HCT) recipients. Two-thirds of adults have been exposed to CMV, generally in childhood, with lifelong viral latency established following the initial infection. In immunocompromised individuals, such as transplant recipients, CMV often reactivates during the post-transplant period when the immune system is weak. CMV itself is immunosuppressive and reactivation of the virus can predispose a person to other opportunistic infections. No therapies are approved for the prevention of CMV in HCT recipients.
Chimerix is a biopharmaceutical company dedicated to discovering, developing and commercializing novel, oral antivirals in areas of high unmet medical need. Chimerix's proprietary technology has given rise to brincidofovir (CMX001), a clinical-stage nucleotide analog lipid-conjugate, which has demonstrated potent antiviral activity and safety in convenient, orally administered dosing regimens. Chimerix is currently enrolling SUPPRESS, a Phase 3 study of brincidofovir for the prevention of cytomegalovirus (CMV) in adult hematopoietic cell transplant (HCT) recipients. In addition, Chimerix is enrolling the pilot portion of the Phase 3 AdVise trial of brincidofovir for treatment of adenovirus (AdV) infection. Chimerix is also working with BARDA to develop brincidofovir as a medical countermeasure against smallpox. For further information, please visit Chimerix's website, www.chimerix.com.
Statements contained in this press release regarding matters that are not historical facts are "forward-looking statements" within the meaning of the Private Securities Litigation Reform Act of 1995. Because such statements are subject to risks and uncertainties, actual results may differ materially from those expressed or implied by such forward-looking statements. Risks are described more fully in Chimerix's filings with the Securities and Exchange Commission, including without limitation its most recent Quarterly Report on Form 10-Q, its most recently filed Current Reports on Form 8-K and other documents subsequently filed with or furnished to the Securities and Exchange Commission. All forward-looking statements contained in this press release speak only as of the date on which they were made. Chimerix undertakes no obligation to update such statements to reflect events that occur or circumstances that exist after the date on which they were made.
CONTACT: Joseph T. Schepers Executive Director, Investor Relations and Corporate Communications firstname.lastname@example.org 919-287-4125Source:Chimerix, Inc.