Medical Dynamics

The Pink Sheet

“FDA Faults Cytogam Sales Literature For Unsubstantiated Long-Term Survival Claim”

July 23, 2009

An efficacy claim in sales literature cannot be based on a trend in a clinical trial, FDA informed CSL Behring in an untitled letter objecting to sales literature for the company’s Cytogam .

FDA questions several survival claims in a Slim Jim sales aid, including a statement that Cytogam (cytomegalovirus immune globulin intravenous, human) “was associated with increased 1-year and long-term survival of liver transplant recipients.”

A 1997 trial demonstrated increased one-year survival in liver transplant patients given CMVIG, notes the letter from CBER’s Office of Compliance and Biologics Quality. But although “there was a trend toward long term survival, the data for survival were not statistically significant beyond one year.”

FDA also objects to the following statements: “Significantly longer survival (79 percent survival at three years vs. 55 percent of those treated with ganciclovir alone,” and “Heart recipients: significantly greater 3-year survival and 3-year freedom from rejection.

A 2001 trial found a three-month improved survival rate for heart, heart-lung and lung transplant patients receiving CMVIG plus ganciclovir compared to those receiving ganciclovir alone, FDA says, but this was a preliminary cohort study using actuarial controls and multiple unadjusted endpoints.

Cytogam is indicated for prophylaxis of cytomegalovirus disease associated with transplantation of kidney, lung, liver, pancreas and heart. Labeling also says its use as a prophylactic should be considered in combination with ganciclovir when transplanting lung, liver, pancreas and heart from CMV seropositive donors into seronegative recipients.

The agency also objects to a claim that heart and lung transplant recipients receiving Cytogam had fewer deaths from obliterative bronchiolitis, noting that this condition is “not well-defined as having an association with CMV infections.”

A suggestion that Cytogam is efficacious for ganciclovir-resistant CMV disease is unsubstantiated, the agency adds, as is the suggestion that dual therapy is no riskier than ganciclovir alone.

Product labeling states that the addition of Cytogam to antiviral monotherapy, such as ganciclovir, “may expose the patient to toxicities and other risks associated with intravenous immune globulin therapy,” FDA points out.

CSL Behring acquired Cytogam from MedImmune in 2006 for an up-front payment of $50 million plus potential milestones. Launched in 1992, the biologic was MedImmune’s first commercial product.