Brincidofovir Shows On-Treatment Antiviral Effect in HCT Setting Despite Trial Not Meeting Primary Endpoint
Company to Host Conference Call on
As reported in
These data were presented today at the BMT Tandem Meetings, the combined annual meetings of the
The SUPPRESS trial was a double blind, placebo-controlled study in which 452 subjects at high risk for CMV were randomized and received brincidofovir or placebo twice-weekly for up to 14 weeks following allogeneic HCT, and then followed off drug for 10 weeks after treatment.
The lead investigator for SUPPRESS, Dr.
The failure to meet the SUPPRESS trial's endpoint of prevention of CMV infection at Week 24 appears to be associated with CMV events in the post-treatment period among subjects on the brincidofovir arm, driven by higher use of corticosteroids and other immune suppressing therapies for the treatment of presumptive graft versus host disease (GVHD). GVHD is a potentially life-threatening condition in which donated bone marrow or stem cells view the recipient's body as foreign and attack the host. Diarrhea can be a symptom of GVHD in the gut, and is also a known side effect associated with brincidofovir that can be managed by a temporary dose-interruption, as described in the safety monitoring and management plan (SMMP) developed during the Phase 2 trial. In the SUPPRESS trial, diarrhea in brincidofovir-treated patients was more frequent and often presumed to be gut GVHD and was treated with corticosteroids, rather than temporarily interrupting study drug according to the SMMP. Among patients who were managed according to the SMMP, significantly fewer CMV infections and lower mortality were observed.
There was an eight-fold increase in the use of corticosteroids through Week 14 in the brincidofovir arm (median cumulative 26 mg/kg prednisone equivalent) compared to the placebo arm (median cumulative 3 mg/kg prednisone equivalent). The use of corticosteroids and other immunosuppressive therapies for the treatment of GVHD is known to increase the risk of infections, including CMV infections that occur when patients discontinue antiviral therapy. The rate of CMV infections thus was higher in the brincidofovir arm between Weeks 14 and 24 (22 percent versus 11 percent on placebo), when patients were no longer on study drug.
Of note, among patients who either underwent T-cell depletion or received alemtuzumab/ATG (approaches that decrease the risk of GVHD), those who were randomized to receive brincidofovir showed a lower incidence of CMV when compared to placebo, at a rate consistent with what was observed in the Phase 2 study of brincidofovir in the HCT setting.
Among the secondary efficacy endpoints, brincidofovir was not shown to prevent infection with non-CMV DNA viruses, such as BK virus. There were no statistically significant differences in all-cause mortality in the trial (15.5 percent in the brincidofovir arm, 10.1 percent in the placebo arm, p=0.12); the numerical differences appear to be driven by higher use of corticosteroids and other immunosuppressive therapies in the subjects who received brincidofovir.
From a safety perspective, the most common adverse events reported for subjects randomized to brincidofovir were acute GVHD (presumed on the basis of symptoms or with biopsy), gastrointestinal (GI) events (predominantly diarrhea), and liver enzyme abnormalities. Although the rate of reported gut GVHD in the Phase 2 study of brincidofovir was higher than that in the placebo cohort, the excess was driven by the overdiagnosis of GVHD based on diarrhea alone. Incorporation of the Safety Monitoring and Management Plan (SMMP) in the final cohort of the Phase 2 study of brincidofovir 100 mg twice-weekly allowed 90 percent of subjects to successfully resume brincidofovir dosing. As seen in Phase 2, there was no evidence of bone marrow toxicity, kidney toxicity, or viral resistance to brincidofovir observed in the SUPPRESS trial.
"We are disappointed that the SUPPRESS trial did not confirm the benefits of brincidofovir in preventing CMV in these high-risk HCT recipients, but we are encouraged by the clear antiviral effects of brincidofovir during the on-treatment period, and in key subgroups of higher-risk patients in this study. We also saw more favorable results when the SMMP was appropriately implemented. With the promising data to date for brincidofovir in adenovirus and
smallpox, we continue to believe in the near-term potential of brincidofovir to address DNA viral infections in HCT recipients and in other at-risk populations," said
Next Steps for the Brincidofovir Clinical Program
As previously announced in
In light of the unexpected results in
SUPPRESS, including the lack of confirmation of the activity against BK virus,
"We remain committed to establishing the best path forward for the evaluation of brincidofovir in solid organ transplant patients, including kidney transplant recipients," said
Conference Call and Webcast
Chimerix's management team will host a live conference call and webcast at
A live webcast of the call and accompanying presentation slides will also be available on the Investors section of the Company's website, www.chimerix.com and an archived webcast will be available on the
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 that there may not be a viable continued development path
for brincidofovir, 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. 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
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Jesse BaumgartnerStern Investor Relations Jesse@sternir.com 212-362-1200 Media: Becky Vonsiatsky W2O Groupbvonsiatsky@w2ogroup.com 413-478-2003
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