FDA approves modernized labeling for ViroPharma's Vancocin Capsules

ViroPharma Incorporated (Nasdaq: VPHM) today announced the modernization of labeling for Vancocin® (vancomycin hydrochloride, USP) Capsules made effective through the U.S. Food and Drug Administration's (FDA) approval of a supplemental new drug application (sNDA).  The company also provided updates on ViroPharma's ongoing citizen petition and litigation with the FDA regarding Vancocin.

Vancocin Labeling Changes

Through the sNDA approval, Vancocin's label for the first time includes clinical safety and efficacy data for Vancocin in treating currently circulating strains of Clostridium difficile, including the BI/NAP1 strain.  Vancocin's labeling now includes important safety and efficacy data from 260 patients with C. difficile associated diarrhea (CDAD) treated with Vancocin in two pivotal studies of Genzyme Corporation's investigational drug, tolevamer.  The Vancocin arm of the trials provides important information to help ensure appropriate use of Vancocin. ViroPharma purchased exclusive rights to the two studies from Genzyme for which it will pay Genzyme royalties of 10 percent, 10 percent and 16 percent on net sales of Vancocin for the three year period following the approval of the sNDA. 

"This new label provides physicians a better understanding about how to treat and monitor patients suffering from the serious and often life threatening infections that require oral Vancocin therapy," said Vincent Milano, ViroPharma's president and chief executive officer.

Exclusivity Incentives for Antibiotic Treatments

As a result of today's sNDA approval, ViroPharma believes Vancocin meets the requirements for, and thus has, three years of exclusivity, and that generic vancomycin capsules will not be approved during this period.  Under FDA's regulations, labeling changes based on new clinical investigations that are essential to approval of the sNDA and to which the applicant has exclusive rights may be entitled to three years of exclusivity, and generic drug labeling cannot include information protected by such three-year exclusivity.  A generic may seek approval by omitting labeling protected by three-year exclusivity; however, if such omissions render the generic drug less safe or effective, it cannot be approved until the three-year exclusivity expires.

In keeping with FDA efforts to facilitate antibiotic approvals as well as preserve the safety and efficacy of current treatments, today's sNDA approval following ViroPharma's investment in the Genzyme data accomplishes an objective of the law to incent private industry to address a serious public health need - modernizing old antibiotic labeling.  The modernized label approved by the FDA contains important new information for prescribers and patients, including:

• Clinical safety and efficacy data of Vancocin capsules, including efficacy data for the more lethal, epidemic BI/NAP1 strain;
• An instruction to monitor renal function in all patients;
• An instruction that elderly patients should not be prematurely discontinued from treatment, or switched to other therapies; and
• A specific dosing regimen for CDAD.

ViroPharma believes that attempting to omit Vancocin labeling changes protected by exclusivity would render generic versions of Vancocin less safe and effective.  These and other issues regarding the modernized Vancocin labeling and its impact on generic vancomycin applications will be detailed in an upcoming filing to the Vancocin citizen petition.  Ultimately, the decision on a grant of three-year exclusivity and its effect on generic vancomycin capsule approvals resides with the FDA.

Citizen Petition Update

Parallel efforts regarding generic vancomycin capsules include ViroPharma's 2006 citizen petition, which has yet to be answered by FDA. Some recent issues raised in the petition include:

• The work of Omar Vesga, M.D., of the Section of Infectious Diseases at University of Antioquia Medical School and Hospital Universitario San Vicente de Paul in Medellin, Colombia, substantiating the concerns of infectious disease experts that generic vancomycin capsules should not be approved without demonstrating in vivo efficacy.   Vesga showed generic intravenous vancomycin products, despite meeting all standard tests of generic equivalence, nonetheless fail in vivo (Generic Vancomycin Products Fail In Vivo despite Being Pharmaceutical Equivalents of the Innovator; Omar Vesga, et al.; Antimicrob. Agents Chemother. August 2010 vol. 54 no. 8 3271-3279).  This demonstration of generic inequivalence with the simple IV formulations of vancomycin supports the need to require that the more complicated generic vancomycin capsules demonstrate in vivo efficacy.
• The United States Pharmacopeia (USP) agrees with ViroPharma that a modern assay to measure vancomycin capsule dissolution is needed: (http://www.usp.org/USPNF/notices/modernizationofMicrobialAssayProcedures.html).   ViroPharma has explained how without such an assay, FDA's proposed in vitro bioequivalence method for generic vancomycin capsules is unworkable, thus preventing the approval of generic vancomycin capsules.
• FDA Advisory Committee experts emphasized the need for particularly rigorous inspections and cGMP compliance for generic vancomycin capsules approved via FDA's in vitro method. (ViroPharma Incorporated Letter to FDA in re: August 4 meeting of FDA Advisory Committee, Docket No. FDA-2009-N-0664-0047 (Oct 6, 2009)). Vesga's work further underscores the importance of such measures, but to date FDA has not indicated it will accede to the advice of its Advisory Committee experts.

Litigation Update

ViroPharma has two suits pending against FDA regarding Vancocin.  A Freedom of Information Act (FOIA) suit seeking the administrative record of FDA's development of in vitro dissolution as a bioequivalence method for generic vancomycin capsules is currently pending decision in federal district court.   ViroPharma also filed an Administrative Procedure Act (APA) suit alleging that FDA's in vitro bioequivalence method for generic vancomycin capsules is flawed under the APA. Oral arguments on the district court's procedural dismissal of this suit are currently scheduled for January 13, 2012 before the United States Court of Appeals for the District of Columbia Circuit.