Chimerix enrolls 450 in brincidofovir Phase 3 SUPPRESS trial

DURHAM, N.C.—Chimerix, Inc., a biopharmaceutical company developing novel, oral antivirals in areas of high unmet medical need, announced today the successful enrollment of the targeted 450 patients in SUPPRESS, the Phase 3 trial evaluating brincidofovir for the prevention of clinically significant cytomegalovirus (CMV) infection in hematopoietic cell transplant (HCT), also known as bone marrow or stem cell transplant recipients. The company anticipates reporting topline data from SUPPRESS in early 2016.

 

"We have reached our targeted 450 enrolled patients in SUPPRESS, a major milestone for Chimerix that brings us closer to providing potential evidence of brincidofovir's activity against viruses that have such a negative impact on these vulnerable patients," said W. Garrett Nichols, M.D., MS, chief medical officer of Chimerix. "The enrollment of this large trial in less than two years speaks to the need for a new antiviral that is active against CMV and other DNA viruses. There has not been a new antiviral approved in this therapeutic area in over a decade."

 

The lead physician investigator for SUPPRESS, Francisco Marty, M.D., of Dana-Farber Cancer Institute in Boston, said, "If approved, brincidofovir will be the first antiviral indicated for the prevention of clinically significant CMV infections in allogeneic bone marrow transplant patients at increased risk of CMV. Although prevention of CMV infections has long been the objective in transplant medicine, available antivirals have not had the safety profile to allow their use in the broader patient population who remain at risk of CMV in the months following a stem cell transplant. We are extremely grateful to all the patients who have taken part in this landmark study."

 

The primary endpoint of SUPPRESS is prevention of clinically significant CMV infection through the first 24 weeks post-transplant. Important secondary endpoints in the trial include the prevention of clinically relevant infections with other DNA viruses that often coexist in immuno-compromised patients, such as adenovirus, Epstein-Barr virus and BK virus; the prevention of bacterial and fungal infections that can be associated with CMV reactivation; the potential associated benefits of preventing CMV such as decreased rates of re-hospitalizations and other measures of healthcare utilization; and the potential to decrease overall mortality in the critical first months following the transplant.

 

The SUPPRESS trial has enrolled 450 adult HCT recipients who are at increased risk for CMV infection from over 40 of the key transplant centers in the U.S., Canada and Europe. Subjects receive twice-weekly brincidofovir or placebo (2:1 ratio) from the early post-transplant period through week 14 post-transplant, the period of highest risk for viral infections.  The company plans to formally review with the U.S. Food and Drug Administration (FDA) a strategy of submitting a new drug application (NDA) for brincidofovir with efficacy and safety data from both the pivotal SUPPRESS and AdVise trials. The Phase 3 AdVise trial for the treatment of life-threatening adenovirus infection began in March 2014 and has enrolled over 150 patients to date. In an analysis presented earlier this year, more than half of the patients enrolled in AdVise had two or more active viral infections, underscoring the significant risks that transplant recipients currently face. If approved, brincidofovir could be the first antiviral with the safety profile to allow use as a prevention of clinically significant CMV infection and potentially other viral infections in these high-risk patients.

 

More than 70,000 hematopoietic cell transplants (HCT) are performed each year worldwide, most frequently to treat patients with certain cancers of the blood and bone marrow or to address genetic diseases. Due to chemotherapy and the immune suppression associated with HCT, patients are highly susceptible to viral, bacterial and fungal infections. These complications are a significant cause of morbidity and mortality in the months following the transplant, and too often the high risk of infection in the first year after transplant results in patients and their families deciding not to undergo a potentially curative transplant.

 

Cytomegalovirus (CMV) is a member of the herpesvirus family and remains a significant cause of viral infections in transplant recipients. A majority of adults in the U.S. have evidence of a prior infection with CMV which establishes a dormant or latent infection that cannot be cleared. Most individuals have an immune system that is able to prevent CMV from reactivating and causing disease. In individuals with weakened immune systems—such as transplant recipients—CMV commonly reactivates during the first weeks following the transplant, leading to infection of the lungs or other organ systems and increasing the risk of other viral, bacterial and fungal infections. No therapies are approved for the prevention of CMV in HCT recipients because of known toxicities associated with available CMV antivirals, including bone marrow suppression and renal impairment.

 

Chimerix's lead product candidate, brincidofovir, is an oral nucleotide analog that has shown in-vitro antiviral activity against all five families of DNA viruses that affect humans, including the herpesvirus family and adenovirus. Brincidofovir has not been associated with kidney or bone marrow toxicity in over 1,000 patients treated to date. Based on the clinically and statistically significant 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 is also conducting AdVise, a Phase 3 trial in patients with adenovirus infection, which is an often-fatal viral infection with no approved treatment. Chimerix is 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.

 

Chimerix is a biopharmaceutical company dedicated to discovering, developing and commercializing novel, oral antivirals in areas of high unmet medical need. Chimerix's proprietary lipid conjugate technology has produced brincidofovir (CMX001), a clinical-stage nucleotide analog