The commonly found adenovirus poses little problem for healthy people, whose immune systems can fight the respiratory and gastrointestinal infections the virus can cause. But in bone marrow and organ transplant patients, adenovirus often becomes deadly. Their weakened immune systems can’t fight off the virus, which studies show can be fatal in up to 80 percent of such cases.
There are no FDA-approved drugs to treat adenovirus, leaving some doctors to turn to a different drug that is associated with a high risk of kidney damage. But an experimental antiviral developed by Durham, NC, pharmaceutical company Chimerix (NASDAQ: CMRX) is showing potential as a safer alternative. A late-stage clinical trial is still underway and Chimerix is taking an unusual approach to the study, but early results show that the Chimerix drug brincidofovir cut adenovirus mortality rates by more than half.
If the Chimerix drug sounds familiar, it might be in the context of Ebola. Brincidofovir was in the spotlight last fall as one of several experimental antiviral drugs pressed into emergency use treating Ebola patients. But a year ago, Chimerix found itself in the spotlight for a different reason. Then 7-year-old Josh Hardy, whose body was weakened by cancer treatment and a bone marrow transplant, was dying from adenovirus infection. A “#SaveJosh” social media campaign and nationwide news coverage built pressure on the tiny company to release the still unapproved drug under so-called compassionate use. The Virginia boy was eventually administered brincidofovir—not under compassionate use but as the first patient in a late-stage trial of the drug.
The gold standard of drug testing in diseases where no treatments are yet available is a double-blind study that compares patients who receive the experimental drug against a second group receiving only a placebo. But Garrett Nichols, Chimerix’s chief medical officer, says treatment centers and their patients are reluctant to participate in studies where some participants receive only a sham treatment because adenovirus is so deadly for these patients.
The idea gave Chimerix pause as well. “It’s difficult to imagine doing a placebo-controlled trial for an infection with 60 to 80 percent mortality,” Nichols says.
At this time last year Chimerix, which had already taken brincidofovir as far as mid-stage clinical trials in adenovirus, was discussing with the FDA what a late-stage study would look like. Hardy’s case gave the company and regulators “that extra push,” he says, toward agreement on a clinical trial design.
Chimerix is now studying its drug in transplant patients, like Hardy, who have adenovirus infection. But instead of comparing the treatment group against a placebo group, Chimerix is using “historic control.” The group of patients treated with the Chimerix drug will be compared against historic data of adenovirus cases.
Historic controls are typically reserved for drug studies in fatal diseases, such as some rare cancers, Nichols explains. In an effort to make the data as comparable as possible, the adenovirus patients will be compared against those who received the same types of transplants and were treated at the same sites where the current trials are taking place.
In the absence of an FDA-approved treatment for adenovirus, many physicians turn to the intravenously administered drug cidofovir (Vistide), says Michael Grimley, a pediatric hematologist/oncologist at Cincinnati Children’s Hospital Medical Center. The drug is approved to treat cytomegalovirus eye infections in AIDS patients. But Grimley, who is also the principal investigator of the Chimerix adenovirus trial at Cincinnati Children’s, adds that without any alternatives, some physicians consider cidofovir the standard of care for treating adenovirus. The drug, however, brings the risk of kidney damage.
“Everybody I’ve treated with IV cidofovir has significant renal impairment from the treatment and that is troubling,” he says. “It’s a double-edged sword. What you do to get your immune system better has other troubling complications.”