Despite advances in stem cell transplants over the last 30 years, there are no approved treatments for adenovirus, which can be rapidly fatal in immunocompromised patients with
disease. Cytomegalovirus (CMV) remains one of the leading causes of death in the first year following a transplant. Among stem cell transplant recipients, co-infection with multiple dsDNA viruses is common, and is associated with higher mortality.
Additionally, among stem cell and solid organ transplant recipients, approximately 15 to 20 percent are diagnosed with norovirus within the first year after transplant, a diagnosis that has been associated with chronic diarrhea, electrolyte disturbances and graft rejection.
Our lead product candidate, brincidofovir, is a clinical-stage nucleotide analog that has shown broad spectrum in vitro antiviral activity against the most important DNA viruses that affect humans, including adenovirus, the virus that causes smallpox (Variola) and cytomegalovirus (CMV). Brincidofovir tablets, oral suspension and intravenous formulations are in development.
Brincidofovir and Transplant Patients
More than 81,000 stem cell transplants are performed each year worldwide, 38,100 in the European Union and 22,500 in the United States.1
Most frequently, stem cell transplants are performed to treat patients with certain cancers of the blood and bone marrow, or to address genetic diseases—representing a great unmet need for effective therapies that help treat and protect immunocompromised patients.
Opportunistic viruses, including cytomegalovirus, adenovirus and BK virus are common in the general population, including in donors and transplant recipients. Many opportunistic viruses that are associated with transplant patients remain dormant in the host body until reactivated.17
Additionally, nearly two thirds of stem cell transplant recipients experience two or more viral infections, and infection with multiple viruses increases the risk for overall mortality.2
Currently, there are no therapies approved for the treatment of adenovirus. Disseminated adenovirus disease can be associated with a mortality rate of 50 to 80 percent in untreated patients who are undergoing stem cell transplant.4
Chimerix completed the AdVise trial of brincidofovir for the treatment of adenovirus infection in allogeneic
stem cell transplant recipients. View the final data here
. The company has initiated the AdAPT (A
ransplantation) study, a comparative trial of brincidofovir for the treatment of adenovirus in pediatric stem cell transplant recipients. For more information on the AdAPT trial, visit clinicaltrials.gov
Significant morbidity (disease state) and mortality are associated with CMV and other viral infections in the first-year post transplant. A mortality rate of approximately 1 in 5 patients during the first year following stem cell transplant is independent of mortality from relapse of the underlying disease. This 20 percent increase in the hazard for non-relapse mortality is caused by post-transplant complications—including viral infections like CMV in particular—as well as other viral, bacterial and fungal infections, and graft failure.
There are no approved therapies for the prevention of BK virus in kidney transplant or stem cell transplant recipients. Available antivirals are associated with known toxicities, such as bone marrow suppression and renal impairment. The prevalence of BK virus in adults is 65 to 90 percent,18
and detection of BK virus in the urine occurs in 30 to 40 percent of patients after kidney transplant, and in 20 to 80 percent of patients after stem cell transplant.19,20
In patients who have received a stem cell transplant, BK virus can cause significant infections of the bladder and kidney.
In 2011, Chimerix received a grant of $81 million from the U.S. Biomedical Advanced Research and Development Authority (BARDA) to continue exploring the development of brincidofovir (CMX001) as a medical countermeasure to treat potential smallpox outbreaks in the event of a bioterror attack or accidental release. If successful, brincidofovir could be an important contribution to the U.S. national security and public health preparedness for the treatment of smallpox—a virus for which there is no approved treatment.
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