VMAC panel split on Proheart 6 question

ROCKVILLE, MD.—Fort Dodge Animal Health vows to work with the Food and Drug Administration (FDA) to get its voluntarily recalled heartworm preventive back on the market.

Dr. Stephen Sundlof, director of FDA's Center for Veterinary Medicine

An independent review panel on Proheart 6 was split (8-7) when asked to make a decision on questions of safety for the profession's only injectable heartworm medication.

The 15-member panel, organized through FDA's Veterinary Medical Advisory Committee (VMAC), was charged with making a recommendation to FDA on the safety of Proheart 6. The medication was recalled voluntarily late last year due to an increase in adverse reaction reporting. Fort Dodge stands behind the safety of its product.

Dr. Lawrence Glickman, VMD, DrPH, FACE, professor of epidemiology and public health and head of the clinical epidemiology section of Purdue University's School of Veterinary Medicine, presented data reviewing almost 7 million canine visits at more than 400 Banfield hospitals.

Says the agency will review new data from Purdue's Dr. Lawrence T. Glickman, on the safety of Proheart 6.

Glickman's data showed a safety profile similar to two other heartworm preventives on the market.

More than half of VMAC members called for further research to more clearly define the reasons behind serious adverse events leading up to the voluntary recall. Other panel members said the compliance benefits outweighed reported adverse event risks.

Some key findings from Glickman's study include:

• In the analysis, Banfield had administered more than 700,000 doses of ProHeart 6 and a like amount of doses of oral heartworm preventive medications.
• No clinically significant increase was attributed to ProHeart 6 use in the risk of liver-related adverse events, neurological disease, ocular disease, immune-mediated disease, cardiovascular disease, anaphylaxis, inflammatory bowel disease, or death, when compared with two commonly used monthly oral heartworm preventives.
• While ProHeart 6 was associated with an increased rate of some liver-related adverse reactions in the univariate analysis, this increased rate was not found in either the days at risk, or in the multivariate analysis. However, all the heartworm preventives and vaccines were associated with a clinically significant increased risk of allergic reactions in the univariate and multivariate analyses, Banfield reports.
• Mast-cell tumor was the only potential adverse event studied that was independently associated with an increased risk following ProHeart 6 use. However, the absolute magnitude of the risk of mast-cell tumor associated with ProHeart 6 alone, or ProHeart 6 plus a vaccine, was small, (1.2 and 1.9 per 10,000 doses, respectively). Compared with the rate of mast-cell tumor in dogs receiving a vaccine alone, the rate associated with dogs receiving ProHeart 6 plus a vaccine does not appear to be clinically significant, the research says.

VMAC members were asked to answer two key scientific questions:

• "Based on presentations and information provided is Proheart 6 safe for use in dogs?"
• "If there are remaining safety concerns with Proheart 6, what additional avenues of research could be explored to mitigate and/or prevent adverse events?"

Dr. Rami Cobb, vice president of pharmaceutical research and development for Fort Dodge Animal Health reports "Fort Dodge Animal Health will continue to work closely with the CVM to resolve any remaining concerns with the product. We feel strongly the thorough testing, comprehensive analysis of the related data and findings of independent scientific experts have demonstrated ProHeart 6 is safe and effective."

Dr. Will Novak, chief medical officer with Banfield, says, "Based on Dr. Glickman's analysis of scientific data from more than 7 million canine visits at approximately 400 Banfield full-service hospitals, we believe ProHeart 6 is an extremely safe and effective product in preventing heartworm."

"We are very confident in the safety and efficacy of ProHeart 6, and will continue to provide our relevant data in the event the FDA continues reviewing the product," Novak adds.

Adverse events reported to FDA totaled 5,669, which was reported widely by the national news media. Adverse events resulting in death were reported at 485 before the recall. FDA applies an algorithm to assign probability scores to determine the probability that the drug was the probable reason for the adverse event.

Fort Dodge believes that its data of approximately three unfiltered reports for each 10,000 doses sold and independent data of four reports per 10,000 doses administered is an accurate reflection on what was happening in the field.

The VMAC panel included: Drs. Arthur Craigmill, Susanne Aref, Corrie Brown, Mr. Gregory Jaffe, Jack Sherman, Katrina L. Mealey, John J. McGlone, Lisa Nolan, Mark Papich, Richard A. Sams, Charles L. Bennett, Michael I. Luster, John R. Glisson, Sam Groseclose, Tom Nelson, Michael R. Peterson, M. Gatz Riddell and Lauren A. Trepanier.