Chimerix Announces Final Study Design for Phase 3 SUPPRESS Trial of CMX001 for Prevention of CMV Infection
-- CMX001 demonstrated potential clinical utility in prevention of CMV
infection in Phase 2
-- SUPPRESS trial anticipated to begin dosing mid-2013 with topline data
expected in 2015
DURHAM, N.C., April 24, 2013 (GLOBE NEWSWIRE) -- Chimerix, Inc. (Nasdaq:CMRX), a biopharmaceutical company developing novel, oral antivirals in areas of high unmet medical need, announced today the final study design for the Phase 3 SUPPRESS trial of CMX001 in the prevention of cytomegalovirus (CMV) infection following an allogeneic hematopoietic stem cell transplant (HSCT). CMX001 is an investigational oral nucleotide analog lipid-conjugate that has shown broad-spectrum antiviral activity against double-stranded DNA (dsDNA) viruses including all of the herpesviruses, adenoviruses and polyomaviruses.
Since the End of Phase 2 meeting with the U.S. Food and Drug Administration (FDA) in May 2012, Chimerix has been working closely with the FDA on the study design of the Phase 3 SUPPRESS trial, and has now finalized the population, specifics and timing of the primary and multiple secondary endpoints, as well as the dose and duration of
CMX001 therapy. Initial study designs considered that two active doses of CMX001, 100 mg twice weekly and 75 mg twice weekly, be carried forward into the Phase 3 trial in order to mitigate the risk of gastrointestinal side effects. However, results from a Phase 1 trial of
CMX001 administered with food and a Safety Monitoring and Management Plan implemented in ongoing clinical trials supported a decision to explore a single dose of CMX001 in SUPPRESS, 100 mg administered twice weekly.
Following successful screening, SUPPRESS subjects will be randomized to receive 100 mg doses of CMX001 twice weekly or placebo. Chimerix anticipates that SUPPRESS will enroll approximately 450 patients who have evidence of prior CMV infection, with approximately 300 of the 450 enrolled subjects receiving CMX001 (2-to-1 ratio). The final study design dictates that dosing of CMX001 or placebo will begin shortly after subjects receive their stem cell transplants, and does not require evidence of stem cell "engraftment" (evidence of production of blood cells by the new transplant), a safety precaution in the Phase 2 trial of CMX001 and other recent trials of investigational agents for CMV prevention. A review of safety data for CMX001 from earlier trials and from the CMX001 Compassionate Use Program found no evidence of toxicity that would restrict early dosing in the Phase 3 trial, and the ability to begin a potential prevention during the early post-transplant period may decrease CMV infection in patients at risk of early CMV reactivation.
SUPPRESS subjects will receive CMX001 or placebo from the early post-transplant period through Week 14, and will continue to be monitored through Week 24 for evidence of CMV disease or for CMV in the blood at levels high enough to require alternative antiviral therapy.
The recently approved Roche TAQMAN(R) real-time polymerase chain reaction assay will be used to monitor levels of CMV in the blood, with a single measurement of CMV in the blood greater than or equal to 1,000 copies/mL considered failure of CMV prevention in any enrolled subject.
In addition, subjects who are at risk of rapid progression to CMV disease (e.g., recipients of umbilical cord blood stem cells) will have a lower threshold for initiation of an alternative antiviral, reaching the primary endpoint with any CMV level in the blood greater than or equal to 150 copies/mL (the lower limit of quantification of the assay).
SUPPRESS is designed to demonstrate the superiority of CMX001 over placebo in prevention of CMV infection, as no therapy is currently approved for prevention of CMV in HSCT recipients. Failure to prevent CMV reactivation through Week 24 will be the primary endpoint for the trial. The trial is powered to detect a 50% decrease in CMV reactivation in the subjects receiving CMX001 versus those on placebo.
SUPPRESS is anticipated to be conducted at approximately 40 sites, and is expected to begin dosing in mid-2013. Data from SUPPRESS are anticipated in 2015 and, if positive, may support accelerated approval of CMX001 for the prevention of CMV infection.
SUPPRESS Study Design:
"Although great strides have been made in HSCT, we still face approximately 20% non-relapse mortality in the first year after transplant, often related to infection. We are hopeful that through preventing reactivation of CMV, and the toxicity associated with preemptive therapy, we can begin to have a positive impact on the medical risks faced by HSCT recipients," said M. Michelle Berrey, MD, MPH, Chief Medical Officer of Chimerix. "We are enthusiastic about the opportunity to take CMX001 forward into a Phase 3 study in these patients who have such a high unmet medical need."
In a post hoc analysis of the data from the Phase 2 trial of CMX001 for CMV prevention, CMX001 was associated with a stable measure of kidney function in patients with evidence of BK virus (BKV) infection, known to be associated with kidney dysfunction in HSCT and solid organ transplant patients. These data were presented at the BMT Tandem meetings in February 2013, and represent the first evidence of a potential positive clinical effect of CMX001 in the setting of BKV.
Secondary endpoints in the Phase 3 SUPPRESS trial will include measures of CMX001 activity against BKV and other dsDNA viruses that have significant impact on the morbidity and mortality of patients undergoing HSCT.
Chimerix recently completed dosing CMX001 in a Phase 2 trial in pediatric and adult stem cell transplant recipients with adenovirus
(AdV) infection, a potentially fatal viral infection with no available therapies. Data from this trial will be available in the second half of 2013.
Chimerix's lead product candidate, CMX001, is a broad-spectrum oral nucleotide analog that blocks replication of all five families of dsDNA viruses that infect humans, including CMV, AdV, BKV and herpes simplex viruses. In a Phase 2 trial, CMX001 demonstrated potential clinical utility in prevention of CMV infection in high-risk patients who had received a HSCT. Chimerix anticipates initiating SUPPRESS, its Phase 3 trial of CMX001 for the prevention of CMV infection in adults undergoing HSCT, in mid-2013. In December 2012, Chimerix completed enrollment of a Phase 2 trial in pediatric and adult HSCT recipients evaluating CMX001 as a preemptive therapy for AdV disease, an often-fatal infection with no approved therapies. Since 2009, Chimerix has made CMX001 available through a Compassionate Use Program to over
80 medical centers worldwide for the treatment of over 430 patients with life-threatening dsDNA viral infections and no alternative treatment.
Chimerix, a biopharmaceutical company based in Durham, NC, is committed to the discovery, development and commercialization of novel, oral antiviral therapeutics designed to transform patient care in areas of high unmet medical need. Chimerix's proprietary lipid technology has given rise to two clinical-stage lipid acyclic nucleoside phosphonates,
CMX001 and CMX157, which have demonstrated the potential for enhanced activity and safety in convenient, orally administered dosing regimens.
Chimerix's second product candidate, CMX157, an oral nucleotide analog lipid-conjugate for the treatment of HIV infection, was licensed to Merck in July 2012.
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. Such statements include, but are not limited to, statements regarding Chimerix's timing for initiating the SUPPRESS trial, Chimerix's ability to enroll patients for the SUPPRESS trial, Chimerix's ability to contract with various sites for conducting the SUPPRESS trial, Chimerix's ability to follow its final study design for the SUPPRESS trial, Chimerix's ability to collect data from its Phase 2 trials and the SUPPRESS trial and the timing for receipt of such data, the efficacy and side effects of CMX001, the ability of Chimerix to support accelerated approval of CMX001 for the prevention of CMV infection and the positive impact of CMX001 on HSCT recipients.
Risks that contribute to the uncertain nature of the forward-looking statements include: the accuracy of Chimerix's estimates regarding its ability to initiate the SUPPRESS trial; the success of the SUPPRESS trial and Phase 2 trials; the demonstrated efficacy of CMX001 in the SUPPRESS trial and Phase 2 trials; the accuracy of Chimerix's estimates regarding expenses and capital requirements; regulatory developments in the United States and foreign countries; Chimerix's ability to obtain and maintain intellectual property protection for CMX001; and the loss of key scientific or management personnel. These and other risks and uncertainties are described more fully in Chimerix's filings with the Securities and Exchange Commission, including without limitation its Registration Statement on Form S-1 that was originally filed with the Securities and Exchange Commission on March 8, 2013, and the amendments thereto. 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: CHIMERIX CONTACTS:
Rebecca Heath, 919.972.7124
Elizabeth Kelly, 919.972.7109
Posted: April 2013