Shares of ViroPharma Inc. fell 53 percent Monday after antiviral drug maribavir failed to meet its primary endpoint of preventing cytomegalovirus (CMV) disease in a Phase III trial in patients undergoing stem cell transplant.
On a conference call with investors, ViroPharma President and CEO Vincent Milano admitted to being "extremely disappointed and frankly surprised" by the results, which pushed the Exton, Pa.-based company's shares (NASDAQ:VPHM) down $6.47 to close at $5.74.
CMV, a type of herpes virus, can be deadly for immunocompromised patients, such as those undergoing bone marrow stem cell transplants. In a previous Phase II trial, patients receiving maribavir, a benzimidazole riboside, were protected completely against CMV, while those receiving placebo had an 11 percent infection rate.
The randomized, double-blind, placebo-controlled, 681-patient Phase III trial was intended to produce similar results. ViroPharma Chief Scientific Officer Colin Broom explained that the company initially expected to see an infection rate of about 9 percent in the placebo group and somewhere around 3 percent in the maribavir group.
Instead, CMV disease incidence was 4.4 percent for maribavir and 4.8 percent for placebo (P = 0.79). The drug also failed to hit secondary endpoints of decreasing the need for anti-CMV treatment, decreasing graft-vs.-host disease, decreasing mortality and increasing CMV disease-free survival. Subset analyses looking at geography, patient serotype and timing also failed to uncover a benefit with maribavir.
On the bright side, maribavir was well tolerated. The most notable adverse event was taste disturbance. Additionally, Broom noted that there was "some evidence of antiviral activity." He also acknowledged less infection in the placebo group than expected - but he pointed out that there was much more disease in the maribavir group than expected as well.
Neither Broom nor Milano made any attempt to put a positive spin on the data. "These results should certainly not yield anybody encouragement that this could be useful in the stem cell transplant patient population," Milano added.
The data also don't bode well for the company's ongoing Phase III study of maribavir in patients undergoing liver transplantations. That study has enrolled 304 out of a planned 348 patients, and ViroPharma intends to finish the trial, but Broom said the company "cannot go into it with any degree of optimism." (See BioWorld Today, July 6, 2007.)
Analysts are pessimistic as well: Cowen & Co. analyst Rachel McMinn wrote in a research note that she has "no confidence" in the liver transplant trial and has removed maribavir - which she had considered "the key long-term value driver for the company" - from her models.
Milano said ViroPharma will be spending less money on maribavir in 2009 than it initially projected. Plans for a Phase III kidney transplant study and pediatric studies have been scrapped for the time being. That means the company will have "more flexibility than we had hoped, frankly" to consider its business development options, Milano said.
ViroPharma has the money to do some pipeline shopping - the company reported $671.8 million in working capital as of Sept. 30 and was projecting expenses between $124 million and $134 million for 2008. ViroPharma also gets revenues from sales of Vancocin (vancomycin hydrochloride capsules), its market-leading drug for antibiotic-associated pseudomembranous colitis caused by C. difficile and for enterocolitis caused by S. aureus, including methicillin-resistant strains.
Net Vancocin sales were projected at between $235 million and $245 million for 2008 - but the product may soon face competition on several fronts. The FDA issued a draft guidance document concerning the development of a generic version of Vancocin in December, and at least three generic firms are eyeing the opportunity. Analysts have predicted the first generic may launch later this year.
Additionally, on the biotech front, competition may come from Optimer Pharmaceuticals Inc.'s OPT-80, which recently outperformed Vancocin in a Phase III C. difficile trial. (See BioWorld Today, Nov. 12, 2008.)
ViroPharma's pipeline also includes Cinryze (C1-esterase inhibitor), which gained approval last fall as a preventative measure for patients with hereditary angioedema (HAE). The drug originally was developed by Lev Pharmaceuticals Inc., which ViroPharma acquired in a deal that could be worth up to $617.5 million. (See BioWorld Today, July 16, 2008, and Oct. 14, 2008.)
While Cinryze was developed for both prevention and treatment of acute HAE attacks, the FDA asked for additional data in the acute use setting, and a decision now is expected in June. Also angling for approval in the treatment of acute HAE is Dyax Corp.'s Kalbitor (ecallantide, DX-88), which was narrowly backed by an FDA panel last week. The agency is expected to rule on Kalbitor next month. (See BioWorld Today, Feb. 5, 2009.)