Decreased HHV-6 Reactivation Observed Among Oral Brincidofovir Allogeneic Hematopoietic Cell Transplantation Recipients
Results to be Presented at Transplantation and Cellular Therapy Meetings of ASBMT and CIBMTR 2019
DURHAM, N.C., Feb. 22, 2019 (GLOBE NEWSWIRE) -- Chimerix (CMRX), a biopharmaceutical company developing novel antivirals to address life-threatening viral infections, will present data demonstrating that treatment with the investigational therapy, brincidofovir (BCV), reduced the incidence and severity of human herpesvirus 6 (HHV-6) viremia in allogeneic hematopoietic cell transplant (allo-HCT) recipients. Results from this post-hoc analysis of the Phase 3 SUPPRESS trial will be presented Saturday, Feb. 23 at the Transplantation and Cellular Therapy Meetings of ASBMT and CIBMTR 2019 in Houston, Texas.
“HHV-6 is a common viral infection and is a significant concern in transplant patients, particularly in cord blood and other high-risk transplant recipients. These types of transplant are associated with higher rates of HHV-6 reactivation following transplant. Because these patients are immunocompromised, the virus can lead to a number of life-threatening complications, including HHV-6-associated encephalitis—or inflammation of the brain—which can be deadly or result in permanent neurological disability,” said W. Garrett Nichols, MD, MS, Chief Medical Officer of Chimerix and member of the recently created Office of the CEO. “We are encouraged by these data and look forward to further research in this area.”
The post-hoc analysis examined data from 92 patients treated with BCV and 61 patients treated with placebo (PBO) who did not have HHV-6 viremia in the SUPPRESS clinical trial, a randomized, double-blind, PBO-controlled trial of 452 patients evaluating oral BCV for cytomegalovirus (CMV) prophylaxis following allo-HCT. Subjects for this analysis were included if they received at least six doses of BCV or PBO within the first three weeks of the trial. Plasma samples from the first six weeks post-transplant were tested for HHV-6, and levels were compared between subjects who received BCV and those who received PBO. Results included the following:
- BCV reduced the incidence and severity of HHV-6 viremia in allo-HCT recipients
- The cumulative incidence of HHV-6 viremia was significantly lower in subjects receiving BCV; 15 percent of BCV subjects versus 31 percent of PBO subjects had detectable HHV-6 viremia within six weeks after allo-HCT
- Two subjects (2 percent) in the BCV group had HHV-6 viremia >1000 copies/mL compared to 7 subjects (11 percent) in the PBO group
- Both rash (9 percent of BCV recipients versus 26 percent of PBO recipients) and HHV-6 encephalitis (1 case on PBO, none on BCV) were less common in subjects receiving BCV; both of these events are known to be associated with HHV-6 reactivation
These results support further investigation of BCV as preventative treatment to reduce the incidence and severity of dsDNA viruses, including HHV-6, following allo-HCT.
Chimerix's lead product candidate, brincidofovir, is a nucleotide analog that has antiviral activity against all five families of DNA viruses that affect humans, including the herpesviruses and adenoviruses. Brincidofovir has a high barrier to resistance, no myelosuppression and a low risk of nephrotoxicity. Brincidofovir has received Fast Track designation from the FDA and Orphan Medicinal Product Designation from the European Commission for adenovirus, cytomegalovirus, and smallpox. Brincidofovir has Orphan Drug Designation for smallpox.
Human herpesvirus 6 (HHV-6) infects most children within the first three years of life and, like other herpesviruses, establishes latency after primary infection.1 HHV-6 commonly reactivates in immunocompromised patients, and 30 to 70 percent of patients undergoing allo-HCT may reactivate after transplant.2-6 Some of these patients may go on to develop HHV-6-associated encephalitis, or inflammation of the brain, which can result in permanent neurological disability or even death. Most cases of encephalitis are believed to represent reactivation of latent infection, since primary infection in adults is rare.7
Chimerix is a biopharmaceutical company dedicated to discovering, developing and commercializing medicines that improve outcomes for immunocompromised patients. Brincidofovir (BCV, CMX001) uses Chimerix's proprietary lipid conjugate technology. For further information, please visit Chimerix's website, www.chimerix.com.
This press release includes forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995 that are subject to risks, uncertainties and other factors, including the possibility our current or future clinical trials of brincidofovir may not be successful, that FDA and other regulatory authorities may not approve brincidofovir or brincidofovir-based regimens, and that marketing approvals, if granted, may have significant limitations on their use. As a result, brincidofovir may never be successfully commercialized. In addition, Chimerix may be unable to file for regulatory approval for brincidofovir with other regulatory authorities. Similar risks and uncertainties apply to the Company’s development of CMX521.These risks, uncertainties and other factors could cause actual results to differ materially from those expressed or implied by such forward-looking statements. Risks are described more fully in the Company's filings with the Securities and Exchange Commission, including without limitation the Company's most recent Quarterly Report on Form 10-Q 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. The Company undertakes no obligation to update such statements to reflect events that occur or circumstances that exist after the date on which they were made.
1 Tremblay C, Thorner AR. Clinical manifestations, diagnosis and treatment of human herpesvirus-6 infection in adults. UpToDate. Retrieved from http://www.uptodate.com/home/index.html.
2 Ljungman P, Wang FZ, Clark DA, et al. High levels of human herpesvirus 6 DNA in peripheral blood leucocytes are correlated to platelet engraftment and disease in allogeneic stem cell transplant patients. Br J Haematol 2000; 111:774.
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6 Ogata M, Satou T, Kadota J, et al. Human herpesvirus 6 (HHV-6) reactivation and HHV-6 encephalitis after allogeneic hematopoietic cell transplantation: a multicenter, prospective study. Clin Infect Dis 2013; 57:671.
7 Whitley RJ, Lakeman FD. Human herpesvirus 6 infection of the central nervous system: is it just a case of mistaken association? Clin Infect Dis 2005; 40:894.