Chimerix's Broad Spectrum Antiviral Therapeutic, CMX001, Demonstrates Potential To Mitigate BK Virus Associated End-Organ Disease In Clinical Study

RESEARCH TRIANGLE PARK, N.C., July 23, 2012 /PRNewswire/ -- Chimerix, Inc., a biotechnology company developing orally-available antiviral therapeutics, today announced the presentation of data showing that its lead antiviral compound, CMX001, has the potential to reduce end-organ damage associated with BK virus (BKV) in hematopoietic stem cell transplant (HSCT) recipients.  This new retrospective analysis, entitled "CMX001, a Novel Broad Spectrum Antiviral, May Mitigate Signs of BK Virus (BKV) Associated Bladder and Kidney End-Organ Damage," was presented at the 24^th International Congress of the Transplantation Society in Berlin, Germany.

BKV infection is commonly observed post solid organ transplant (SOT) and is associated with renal dysfunction and potential kidney graft loss.  BKV is also known to cause hemorrhagic cystitis (a painful inflammatory bladder condition) in HSCT recipients, but the incidence and impact of BKV infection on bladder or kidney dysfunction in this patient population have been less well characterized.  Herve Mommeja-Marin, MD, Vice President of Clinical Research at Chimerix, presented the BKV data from the Phase 2 Study CMX001-201, which had as its primary objective the evaluation of CMX001 versus placebo for the prevention of cytomegalovirus (CMV) infection in 230 HSCT recipients.  Phase 2 results presented elsewhere have shown that CMX001, at various doses, was active and well-tolerated in the prevention of CMV infection or disease.   

The observations from Study 201 represent the largest retrospective analysis of BKV-associated signs and symptoms collected in a randomized, placebo-controlled trial reported to date.  In Study 201, which evaluated only HSCT recipients, there was a high incidence of BKV infection: BKV was measurable in the urine samples of 55% (126/230) of subjects at some time during the study period.  Of these subjects, 80% (101/126) were positive prior to enrollment.  Subjects who received CMX001 had a reduced incidence of hematuria (defined as > 1+ heme, confirmed on urinalysis) and serum creatinine elevations (an indication of renal impairment) versus placebo, based on analyses of objective measures of end-organ disease.  

With respect to BKV-related effects on the bladder, only 6.4% (6/94) of CMX001-treated subjects with BKV infection developed hematuria versus 25% (8/32) of placebo-treated subjects.  By contrast, in subjects without BKV reactivation, 7.8% (6/77) of CMX001-treated and 3.7% (1/27) of placebo-treated subjects developed hematuria.  These findings support further study of CMX001 for the prevention of BKV-associated hemorrhagic cystitis in HSCT recipients, an important medical condition for which there is no current therapy.

The analysis also highlighted the association of BKV infection with the development of renal dysfunction in HSCT recipients and explored the potential impact of CMX001 prophylaxis on this condition.  In particular, in subjects with BKV reactivation, new onset renal dysfunction [defined as an elevated serum creatinine concentration of >120 mM (>1.36 mg/dL) at end of the study that was at least 25% greater than the baseline value] occurred in 7.4% (7/94) of CMX001-treated subjects compared to 18.8% (6/32) of placebo-treated subjects.  In comparison, new onset renal dysfunction in subjects without BKV reactivation was infrequent in both randomized groups:  7.8% (6/77) of CMX001-treated and 7.4% (2/27) of placebo-treated HSCT recipients.  The data in the placebo-treated subjects suggest that BKV infection may contribute to the development of renal dysfunction in HSCT recipients.  Furthermore, the apparent reduction of renal dysfunction in subjects with BKV reactivation receiving CMX001 prophylaxis supports the initiation of prospectively designed clinical trials evaluating CMX001's impact on preventing kidney dysfunction in HSCT, renal and potentially other solid organ transplant patients.

Taken together with CMX001's previously reported antiviral activity against CMV reactivation, these findings further underscore the potential of CMX001 as a broad spectrum antiviral prophylaxis post-transplantation in HSCT recipients.  In addition, these findings provide a clear rationale for conducting additional studies of CMX001 in the prevention of hemorrhagic cystitis in HSCT recipients and BKV associated nephropathy in kidney transplant recipients, and provide further evidence of the lack of nephrotoxicity of CMX001.

About BK Virus in Study CMX001-201
Subjects were monitored weekly by urine BKV PCR; plasma was tested by BKV PCR if the urine sample was positive.  As part of routine laboratory testing, evidence for microscopic hematuria (dipstick) and serum creatinine concentrations were monitored regularly during the dosing phase.  Subjects were tabulated according to group (pooled CMX001 versus placebo) and BKV status (viruria positive or negative at any time during dosing).  To explore the impact of CMX001 on the emergence of BK virus-associated symptoms, the incidence of hematuria and renal dysfunction was explored. 

About BK Virus
BK virus (BKV) is common in the general population, infecting the majority of adults.  In healthy individuals, the initial infection does not cause symptoms; subsequently BKV remains latent in the kidney or bladder for life.  In immunocompromised individuals, however, the virus can reactivate in the urogenital tract leading to hemorrhagic cystitis and/or kidney damage.  In particular, after kidney transplantation, BKV infection can lead to the loss of the graft.  There is currently no approved therapy for BKV infection.  Reduction in immunosuppression as a means of controlling the infection is the current standard of care post-kidney transplantation, but such reductions are associated with an increased risk of organ rejection.

About Chimerix
Chimerix is developing novel antiviral therapeutics with the potential to improve quality of life for patients in multiple settings, including transplant, oncology, acute care and global health.  The company's proprietary lipid technology platform has given rise to Chimerix's two clinical stage compounds, CMX001 and CMX157, which have demonstrated the potential for enhanced activity, bioavailability and safety compared to currently approved drugs. 

Chimerix's lead candidate, CMX001, is a novel, oral, broad spectrum lipid acyclic nucleoside phosphonate that inhibits double-stranded DNA (dsDNA) viruses including CMV, adenovirus (AdV), BKV, and herpes simplex virus.  CMX001 has completed Phase 2 clinical development for the prophylaxis of CMV and is in Phase 2 development for the preemption and treatment of AdV infection in HSCT recipients.  Antiviral activity from completed and ongoing studies, coupled with the lack of myelotoxicity and nephrotoxicity that are associated with currently available CMV therapies, indicate that CMX001 has the potential to improve outcomes for hematopoietic stem cell and solid organ transplant recipients. 

Chimerix has completed an End of Phase 2 meeting with the FDA for CMX001 and is preparing to initiate Phase 3 clinical development of CMX001 for the prophylaxis of CMV in HSCT recipients.  To date, more than 750 patients have been dosed with CMX001 in controlled clinical trials and open-label treatment protocols.  Under a contract from the Biomedical Advanced Research and Development Authority (BARDA), CMX001 is also being developed as a medical countermeasure to protect against a bioterror threat in the event of a smallpox release. 

CMX157 is a novel lipid acyclic nucleoside phosphonate that delivers high intracellular concentrations of the active antiviral agent tenofovir diphosphate.  Compared to tenofovir, CMX157 is more than 200-fold more potent in vitro against all major HIV subtypes resistant to current therapies, which may allow activity against tenofovir-resistant viruses (e.g., K65R), and against HBV.  CMX157's novel structure results in decreased circulating levels of tenofovir, lowering systemic exposure and thereby reducing the potential for renal side effects.  CMX157 has completed a Phase 1 clinical trial in healthy volunteers, demonstrating a favorable safety, tolerability and drug distribution profile.

Led by an experienced antiviral drug development team, Chimerix is also leveraging its lipid technology and novel chemical library to pursue new medicines for other areas of high unmet medical need.  For a copy of the poster referenced in this press release or for additional information on Chimerix, please visit http://www.chimerix.com.  

SOURCE Chimerix, Inc.

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