Drug to fight virus in transplant patients moves forward in trials

A drug once considered for cancer chemotherapy is advancing in clinical trials to test its effectiveness in fighting a virus from the herpes family that threatens transplant patients.

University of Michigan professors Leroy Townsend and John Drach developed the compound maribavir. It is licensed by ViroPharma, which announced today that maribavir is headed for phase 2 clinical trials for the treatment of cytomegalovirus infection in stem cell transplant patients. New drugs go through three phases of clinical trials before the Food and Drug Administration decides on their approval.

Cytomegalovirus (CMV) is part of the herpes virus family, which also includes the viruses that causes chicken pox, mononucleosis and herpes simplexes 1 and 2. Like other herpes viruses, CMV can remain dormant in the body for long periods of time.

In most people with intact immune systems, CMV causes little to no apparent illness. However, in people with weakened immune systems, CMV can lead to serious complications or death.

Patients who are immunosuppressed following transplant of hematopoietic stem cells, such as a bone marrow transplant or solid organ transplantation, are at high risk of CMV infection, as are AIDS patients, fetuses and newborns. In these patients, CMV can lead to conditions such as pneumonitis or hepatitis, or to complications such as acute or chronic rejection of a transplanted organ. When contracted in utero or at birth, CMV can cause babies to be born with birth defects or impairment such as hearing loss.

ViroPharma Inc. (Nasdaq:VPHM) is looking at the potential effectiveness and safety of the oral antiviral drug for transplant patients in the phase 2 trial. The study will be conducted at up to 15 transplant centers across the United States.

Drach, a biochemist and virologist who is a professor in the schools of dentistry and pharmacy, and Townsend, emeritus professor in chemistry and Pharmacy’s medicinal chemistry, began researching cytomegalovirus in the 1980s, prompted by a National Institutes of Health call for proposals to find drugs to treat CMV infections.

The U-M researchers collaborated with scientists at what is now GlaxoSmithKline, leading to prompt clinical evaluation of maribavir. But advances in treatment of HIV and AIDS patients temporarily slowed interest in the compound and development work ceased. CMV was a common cause of blindness and ultimately death in HIV patients, and as the medical community invented drugs to treat the HIV infection directly, there was less urgency by large pharmaceutical firms to develop a CMV drug.

“We had mixed feelings—naturally we were pleased to see the remarkable progress in treating HIV and the dramatic decrease in death from AIDS-related complications, but we also wanted to see our compound get to market for other people with CMV,” Drach said.

Recently, ViroPharma licensed maribavir, and in February it launched a phase 1 trial to study drug interaction and the drug’s safety in healthy volunteers. ViroPharma hosted an informational session on July 21 about CMV; click here to download the PDF: http://www.viropharma.com/TEACH%20IN%20MASTER_%20FINAL_FOR%20PRINT.pdf.

More than 30 years ago, Drach teamed with fellow dentistry professor Charles Shipman to study herpes simplex and to discover drugs to treat resulting diseases that manifest orally as cold sores. When Townsend came to Michigan in 1979, his focus had been primarily the design and synthesis of new anticancer drugs.

Townsend agreed to peruse his library of anticancer compounds so Drach could test them for potential effectiveness against CMV. Chemotherapy drugs work by killing cells and the scientists hoped that if Townsend’s compounds had not been effective in killing cancerous cells, maybe they would instead work to block replication of virus cells without killing healthy cells. In fact, that was the case for the class of compounds to which maribavir belongs.

Maribavir works differently than other CMV treatments. It inhibits the function of three previously undiscovered CMV genes.

The collaboration of faculty from dentistry and pharmacy to study potential cancer drugs for their effectiveness in treating a herpes virus is a classic example of what researchers say is a major strength of U-M: the ease of teaming with others outside their discipline to find new approaches to questions bigger than any one way of answering them.