Viral respiratory infections are a major concern for immunocompromised patients, in whom such infections are difficult to treat and can lead to pneumonia and even death. Although few treatment options for such infections have been available, clinical trials of promising new therapies are now enrolling immunocompromised patients with two common respiratory viruses: respiratory syncytial virus (RSV) and parainfluenza virus (PIV).
RSV and PIV infections start in the upper respiratory tract and can progress to the lungs. Especially vulnerable are leukemia patients and patients who have undergone hematopoietic stem cell transplantation, said Roy Chemaly, M.D., a professor in the Department of Infectious Diseases, Infection Control, and Employee Health at The University of Texas MD Anderson Cancer Center. “When these infections progress to pneumonia, immunocompromised patients are at high risk of dying,” he said.
“At MD Anderson, we see around 300 cases of upper or lower respiratory tract RSV infections each year, mostly between October and March,” Dr. Chemaly continued. “We see about as many cases of PIV, but most of these occur in the spring and summer.” Symptoms of RSV and PIV infections are similar to those of other respiratory viruses, and the differential diagnosis is made by polymerase chain reaction testing.
Once an RSV or PIV infection is diagnosed in an immunocompromised patient, its treatment can be a challenge. Little has changed in the treatment of RSV or PIV for the past 15 years, but Dr. Chemaly said research to improve treatment for both viruses is under way. He is the principal investigator of several clinical trials at MD Anderson that are currently enrolling immunocompromised patients with RSV or PIV infections.
The current treatment for RSV is aerosolized ribavirin, which is approved by the U.S. Food and Drug Administration (FDA) for treating RSV infections in children but is often prescribed off-label for immunocompromised adults. During this treatment, a patient must remain in a plastic tent at least 9 hours per day for 5–10 days. “This treatment works, but it is expensive and cumbersome,” Dr. Chemaly said. “So we are very excited about the possibility of treating RSV with an oral drug.”
In an MD Anderson–only phase II clinical trial, patients who have undergone hematopoietic stem cell transplantation and have RSV infections of the upper respiratory tract that require treatment are randomly assigned to receive aerosolized ribavirin or oral ribavirin. “This could change the way we treat patients, if we are able to move away from aerosolized ribavirin,” Dr. Chemaly said.
Another candidate for the treatment of RSV infection is GS-5806, a long-acting oral drug that blocks fusion of the viral envelope with host cells. The drug is under investigation in two multicenter randomized controlled trials for patients who have undergone hematopoietic stem cell transplantation and have RSV infections. One of the trials is for patients with infections of the upper respiratory tract; the other is for patients with lower respiratory tract infections.
In both GS-5806 trials, patients are randomly assigned to receive five doses of the drug or placebo over 17 days. The primary outcome measure for both trials is change in RSV nasal viral load; secondary measures include number of days without supplemental oxygen. For the trial enrolling patients with upper respiratory tract infections, Dr. Chemaly said, “We hope to prevent the virus from progressing to the lungs.”
Unlike RSV, PIV infection has no FDA-approved drugs for its treatment. “There’s nothing for patients with this infection, so there is a real unmet need,” Dr. Chemaly said.
Fortunately, an inhaled drug called DAS181 shows promise. DAS181 prevents the spread of PIV by blocking the virus from binding with sialic acid receptors in epithelial cells in the respiratory tract.
A multicenter phase II study of DAS181 is now enrolling patients who have undergone chemotherapy or stem cell, heart, or lung transplantation and have lower respiratory tract PIV infections necessitating supplemental oxygen.
Patients in the study are randomly assigned to receive one dose per day of DAS181 or placebo for 10 days. “Patients have a two in three chance of getting the study drug and a one in three chance of getting the placebo,” Dr. Chemaly said.
Interim results of the study are not yet available, but Dr. Chemaly is confident that the drug will benefit patients. “We have used DAS181 in our compassionate use program,” he said, referring to the FDA policy that allows expanded access to investigational drugs for individual patients when a clinical trial is not available, “and we’ve seen good results without many side effects.”
Dr. Chemaly is encouraged by the recent increase in new treatments for RSV and PIV infections. “For 10–15 years there was not much research on drug development for these viruses,” he said. “But in the past few years pharmaceutical companies have begun developing drugs that may improve outcomes for immunocompromised patients with RSV and PIV infections.”
For more information, contact Dr. Roy Chemaly at 713-745-1116.
OncoLog, September 2015, Volume 60, Issue 9