ViroPharma Inc. began a second Phase III trial of the anti-CMV agent maribavir, this one to prevent infection in patients undergoing liver transplantations.
The drug, now named Camvia, will be evaluated against oral ganciclovir for preventing cytomegalovirus disease in more than 300 patients who have undergone liver transplantations. ViroPharma in September began a Phase III trial of Camvia to evaluate the oral agent against placebo in 500 patients undergoing allogeneic stem cell transplantations, a study also designed to assess prophylactic efficacy.
Michel de Rosen, president, chairman and CEO of ViroPharma, said the two studies are designed to support registration of the product with the FDA, with the goal being a new drug application filing in 2009. He said the anti-CMV product may have applications beyond the areas covered by the studies, but the focus now is to get approvals for use in stem cell and solid organ transplant patients.
The trial in liver transplant patients will be run at about 60 centers in the U.S. in patients at high risk of developing CMV disease, such as when the donor is HSV positive and the recipient negative. If CMV infection or CMV organ disease occurs during the drug administration period, patients would be taken off the drug and managed according to standard treatment practices.
ViroPharma, of Exton, Pa., said that, based on published data, about 12 percent of patients in the oral ganciclovir arm are expected to get CMV disease within the six-month post-transplantation time frame defined as the primary endpoint.
Secondary endpoints in the trial include time to onset of CMV infection and disease, the incidence and time to onset of anti-CMV therapy and survival without CMV infection or disease.
The study also will evaluate adverse effects, which limit the use of current therapies.
De Rosen told BioWorld Today there is no drug approved for prophylactic use in liver transplantations, although Valcyte (valganciclovir) from F. Hoffmann-La Roche Ltd. is used in other solid organ transplants.
In stem cell transplants, he said, there is no prophylactic approach (hence the placebo control in that study), with treatment initiated only after an infection is identified. "We're trying to change the paradigm of the way the disease is being addressed," de Rosen said.
Camvia is the lead drug in development from a new class called benzimidazole ribosides. Unlike existing agents that inhibit CMV DNA polymerase, Camvia is designed to inhibit viral DNA assembly and inhibit egress of viral capsids from the nucleus of infected cells. It demonstrated 100 percent protection against CMV reactivation in a 111-patient Phase II trial in patients undergoing allogeneic stem cell transplantation, vs. an 11 percent infection rate in the placebo arm. It also demonstrated favorable safety and tolerability.
ViroPharma licensed rights to Camvia in August 2003 from GlaxoSmithKline plc in a deal that entailed $3.5 million up front to GSK, along with potential milestone and royalty payments. GSK maintained rights only in Japan. ViroPharma, which plans to commercialize the product itself in the U.S., recently said it changed its strategy for Europe and now plans to sell it there, too.
De Rosen said that decision followed the strong Phase II data, along with a realization that marketing efforts in Europe would be similarly focused to those needed in the U.S.
The company also took into account experience in the European market already held by top officials at ViroPharma.
The company plans to out-license the product for markets other than the U.S., Europe and Japan.
"We already have started to create a presence in Europe, and started dialogue with regulatory authorities in Europe to define the path forward," de Rosen said, adding that the two ongoing studies would be expected to support regulatory requirements in Europe.
Camvia recently was selected as the brand name for the product. De Rosen said a big reason was the prominence of "CMV" in the name, giving a clear message to physicians and others. Company officials also liked the connotations of "via," Italian for path, such as in "path to health"; and "vie," French for "life."
William Roberts, senior director of corporate communications at ViroPharma, said the plan later contemplates that Phase I/II trials in other solid organ indications - such as kidney, lung, heart and pancreas - would be enough to support supplemental NDA filings, assuming the liver data are positive. The liver indication, he pointed out, is the only one now for which Valcyte is not approved.
Behind Camvia, ViroPharma is developing HCV-796, which is in Phase II trials for treating hepatitis C virus. Initial Phase II data are expected in the fourth quarter. ViroPharma retains U.S. co-promotion rights to the product, which is partnered with Wyeth, of Madison, N.J.
ViroPharma also has the approved product Vancocin, a capsule formulation of the antibiotic vancomycin, which produced about $49 million in sales in the first quarter. ViroPharma officials projected Vancocin sales of $195 million to $205 million for the year.
The company, which reported net income of $22 million in the first quarter, sold $250 million in convertible notes earlier this year, leaving it with about $480.6 million in cash and equivalents as of March 31.
ViroPharma had about 69.8 million shares outstanding. Its stock (NASDAQ:VPHM) gained 11 cents Thursday to close at $14.48.