New Antiviral Protects Against CMV After Stem Cell Transplants

Zosia Chustecka

September 25, 2013

Prophylactic use of an investigational antiviral product has been shown to prevent cytomegalovirus (CMV) events in patients who have undergone allogeneic hematopoietic cell transplants (HCT). These transplants, usually from donated bone marrow, are commonly used in the treatment of leukemia and lymphoma.

The new product, CMX001 (under development by Chimerix), is a lipid conjugate containing the antiviral agent cidofovir, and is taken orally. The results come from a phase 2 trial involving 230 patients, conducted across 27 centers in the United States, and published in the September 26 issue of the New England Journal of Medicine.

The results show a significant reduction in the incidence of CMV events (which includes CMV disease and detectable CMV levels in the blood) in HCT recipients who were treated with CMX001. These CMV events were reported by 10% of patients on the new drug, compared with 37% of patients on placebo (P = .002).

"The results show the effectiveness of CMX001 in preventing CMV infections in this group of patients," lead author Francisco Marty, MD, from the Dana-Farber Cancer Center and Brigham and Women's Hospital in Boston, commented in a statement. "Because CMX001 is known to be active against other herpes viruses and against adenoviruses that sometimes affect transplant patients, it may be useful as a preventive or treatment agent for those infections as well," he added.

"Our findings require confirmation in phase 3 studies," the researchers write.

Less Toxic Antiviral Prophylaxis

While CMV is a common infection, most people are unaffected by it as the virus is usually held in check by the immune system. However, once the immune system is compromised, CMV infection can cause problems, including pneumonia, diarrhea, and digestive tract ulcers.

Patients who undergo allogeneic HCT have their immune system destroyed by radiation and/or chemotherapy in preparation for receiving the transplant, and are very vulnerable to infection. "Between 3% and 5% of allogeneic HCT patients develop CMV disease within 6 months of transplantation, and a small number of them may die from it," Dr. Marty explained.

Antiviral drugs are used, and when they are administered at the first sign of CMV infection, can often forestall CMV disease, Dr. Marty explained, but they have adverse effects, including kidney damage and myelosuppression. "There clearly is a need for better treatments with fewer adverse effects," he said.

One of the agents that is currently used is valganciclovir, which is approved for prophylaxis against CMV infection after solid organ transplantation. However, its use is limited by myelosuppression, particularly after HCT, the researchers write.

The most common adverse effect reported by patients receiving CMX001 was diarrhea. "Myelosuppression and nephrotoxicity were not observed," the researchers report.

The study was funded by Chimerix.

N Engl J Med. 2013;369:1227-1236. Abstract


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