Seldom can one say $3.8 million is just the tip of the iceberg, but a newly awarded grant from Gilead Sciences, Inc. is just that. MUSC transplant surgeon Kenneth Chavin, M.D., Ph.D., says the true value of the multi-center drug trial is closer to $26 million, including $22 million in free drugs provided by the pharmaceutical company.
As the trial's principal investigator, Chavin wants to know whether the drug Harvoni, which received approval from the Food and Drug Administration for the treatment of the hepatitis C virus, will retain its 97 to 99 percent cure rate for patients who have undergone a liver transplant.
HCV, an RNA virus that inflames liver cells, often leads to cirrhosis - or scarring - of liver tissue. It is the primary cause of liver disease in adults and by far the most common reason for a patient to need a transplant. Unfortunately, liver transplant alone may simply delay the worst unless the virus itself is cured.
"One of the leading causes of graft failure - the failure of the organ to thrive - in liver transplant patients is a recurrence of HCV, including fibrosing cholestatic hepatitis C, a rapidly progressing recurrence with a very high mortality rate," Chavin said. "If HCV recurs within two years, then the patient is not considered a good candidate for another transplant; more than likely, it will occur again, and you'll have lost two livers and a patient in the end."
Such stark assessments highlight the need for good treatments for HCV among liver transplant patients. Other drugs do exist, Chavin explained, but they require longer courses of treatment and are much more poorly tolerated after transplant than preliminary results show Harvoni to be.
"Side effects of the old drugs include severe fatigue, nausea, body aches. The old drugs basically induce continuous flu-like symptoms in an attempt to cure the virus," Chavin said. "Direct-acting antiviral therapies like Harvoni offer patients better outcomes with fewer side effects."
The trial is the first of its kind in the United States and will include 220 patients at four centers across the country: MUSC, Emory, Georgetown and the University of Pittsburgh Medical Center. Researchers at MUSC, including Chavin, transplant hepatologist Kimberly Beavers, M.D. and pharmacist James Fleming, PharmD, are taking the lead and have written protocols for each of the centers to follow.
Chavin said MUSC was a natural choice to head up the trial, even among other world-renowned institutions. "MUSC's transplant group has always been involved in clinical research. We have a track record of multiple, successful investigator-initiated trials with big pharma as our sponsor. And we have the appropriate infrastructure in surgery, medicine and pharmacy to lead a trial like this. It's because of that and our interest in serving our patients that I think we were selected."
Coordinating such a complex trial, not only across areas within MUSC but also across different organizations, has been a challenge, but not one for which Chavin was unprepared. "Transplant is a multidisciplinary care team," he explained. "We have proven track records in the areas of collaborative academic as well as clinical work. From the presentation of a patient with whatever disease he or she may have through the operation and post-transplant care, we have ongoing robust interactions with colleagues across the institution, and this trial is just an extension of that. Just one example, the Data Coordination Unit, housed in the Department of Public Health Sciences, is playing a key role in assisting with project management for the study across all of the sites."
Fleming, who is the lead pharmacist on the trial, hopes it will form the basis for a new working relationship between the four centers. "The new research relationship between MUSC, Emory, Georgetown, and UPMC will hopefully result in more collaborative research opportunities in the future," he said.
Chavin hopes to begin open enrollment for the trial by April 1. The other three centers will follow within 30 to 60 days. He said the trial is novel and unique, especially considering the cost of the medication provided, which typically runs in excess of $100,000 per patient for a course of treatment.
While future transplant patients may not have the good fortune to receive free medicine, Chavin said the drug is still a good deal. "A one-time cost of $100,000 saves all the cost of having liver disease, which can be millions of dollars. For a liver transplant, the average is $150,000 to $200,000, not including hospitalizations and complications. It's very cost effective in the long run, both individually and from a public health perspective, to eradicate HCV in the general population."
The trial is called LIVE-C-Free: Early and late treatment of hepatitis C with sofosbuvir/ledipasvir in liver transplant recipients, and its ClinicalTrials.gov identifier is NCT02631772.