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picked up by a protein that takes it right to the kidney, leading to kidney damage, Grimley explains. Brincidofovir never latches on to that protein so the kidney never sees the cidofovir.
To produce brincidofovir, Chimerix binds cidofovir with a lipid molecule that makes it absorbable in the gut. This means Chimerix can make its drug into a pill—something that is not possible with regular cidofovir, Nichols says. The lipid also shepherds the drug directly into the target cells, where it then releases the cidofovir molecule, which means that those cells receive much higher levels of the drug compared with intravenous cidofovir.
The Chimerix drug was developed in the laboratory of Karl Hostetler at the University of California San Diego. Hostetler developed the lipid technology under a government contract for use in a smallpox antiviral. That program, funded by the Biomedical Advanced Research and Development Authority, continues at Chimerix today. Chimerix’s work in transplant patients came from the company’s search for other applications of its drug.
So far, Chimerix has data from 85 patients who received brincidofovir in its Phase 3 adenovirus study. In the study, the mortality rate in bone marrow transplant patients with disseminated adenovirus infection was 37 percent after 75 days. Brincidofovir has gastrointestinal side effects, including diarrhea. Grimley says those side effects were known but they occurred less frequently compared with their occurrence in an earlier study. Three patients dropped out of the Phase 3 trial due to those side effects, but Grimley says it’s possible that they were instead suffering the effects of adenovirus in their intestinal tract. Most important, he says, there was no evidence of damage to the kidneys or bone barrow. The study, which is enrolling both children and adults, is expected to include 200 total patients.
Chimerix hopes that brincidofovir finds applications in other viruses. The company is also in a separate late-stage clinical trial studying the drug’s ability to prevent cytomegalovirus infection in bone marrow transplant patients. This placebo-controlled study will be important in filing for FDA approval of the drug, Nichols explains, since Chimerix plans to file drug applications in adenovirus and cytomegalovirus at the same time. Nichols says efficacy and safety data from the cytomegalovirus trial will help support the company’s submission of the drug in adenovirus. The company expects to have data from the cytomegalovirus study in about a year.
Meanwhile, the adenovirus study results so far help support Chimerix’s case for applying brincidofovir in multiple viruses. Grimley says half of the patients enrolled in the adenovirus study suffered from additional viral infections.