Chimerix has scuttled two Phase III studies of its antiviral brincidofovir after studying the data from the first late-stage failure, which bludgeoned its share price ($CMRX) as the biotech sector fell out of favor with investors.
On Sunday the Durham, NC-based company outlined the data points that forced the clinical retreat, noting a relative drop in the rate of cytomegalovirus infection during 14 weeks of treatment (24% vs. 38% for the placebo group) followed by a spike in the 10-week follow-up stage that eclipsed CMV infections seen in the placebo arm (22% vs. 11%). That teeter-totter effect left the CMV infection rate for patients undergoing hematopoietic cell transplantation (HCT) virtually equal between the drug arm and the placebo group, while deaths in the drug arm outpaced the placebo group.
As a result, the biotech says it has now ended two related Phase III studies and will concentrate on a Phase II trial to provide some added insights on how to best move forward on the drug, with a special emphasis on its preclinical IV formulation.
Uncertainty over the future of the drug--which was once the subject of a viral campaign for compassionate use--has driven the value of the stock down to a fraction of its old high, a reflection of the sudden distaste for risk on Wall Street.
Investigators for the study say the failure was caused by a rise in the rate of diarrhea in the drug arm. As diarrhea is a symptom of graft-versus-host disease (GVHD), physicians used corticosteroids more frequently, even though it's also an adverse event associated with the drug, which can be treated by suspending dosing. That use of corticosteroids due to an over-diagnosis for GVHD scuttled the drug's effect, they claim, by increasing the risk of infection.
There were other problems, as well, including no evidence of a reduced rate of non-CMV DNA viruses, such as BK virus. The all-cause death rate was 15.5% for brincidofovir and 10.1% in the placebo arm.
"While the data confirm an anti-CMV effect with brincidofovir ("brinci") and somewhat addresses the company's proposed explanation for the outcome (diarrhea masking as acute GvHD driving higher use of steroids), they do not fully address the higher rates of morbidity," notes Barclays' Geoff Meacham in a note early Monday.
What's ahead for this drug? Chimerix plans to roll back the program to Phase II as it studies the development of an IV formulation that could prevent the diarrhea and possibly avoid the reaction that caused the use of corticosteroids. And it will further explore its use to prevent infections after solid organ transplants.
Brincidofovir--which is the company's sole focus--is a lipid-conjugated version of cidofovir specifically designed to amp up the antiviral impact with a pill while sparing kidneys from a toxic threat. Its ability to get into cells more effectively than cidofovir has been touted as a far more effective counterpunch to 5 DNA viral infections. In a small open-label pilot study driven by the compassionate-use case of young Josh Hardy, the antiviral was successful in dramatically reducing the rate of adenovirus infections. But that study may also ultimately raise fresh doubts about the value of running small, impromptu studies without a control arm.
|Chimerix CMO W. Garrett Nichols|
Still, don't look for anyone associated with the company to appear alarmed or skeptical at this stage.
"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," said Dr. W. Garrett Nichols, Chimerix's CMO, in a statement. "We also saw more favorable results when the [safety monitoring and management plan] 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."
- here's the release