# Presentation: 727281

## ProHeart 6Safety Assessmentby Fort Dodge Animal Health

**January 31, 2005**

## Rami Cobb, BVSc (Hons.) MACVSc

**Rami Cobb, BVSc (Hons.) MACVSc**
**Vice President**
**Pharmaceutical Research & Development**
**Fort Dodge Animal Health**

## ProHeart 6 Introduction

- Active ingredient: moxidectin
- Macrocyclic lactone
- Anthelmintic agent
- Dogs, horses, cattle, sheep, swine
- Co-development with WHO for humans
- Onchocerciasis (river blindness)

## ProHeart 6 Introduction

- Innovative Product
- A single dose provides 6 months protection from heartworm disease caused by
*	**Dirofilaria immitis*
- Treats existing hookworm infections
- Overcomes compliance failures associated with monthly heartworm preventives

## MoxidectinExtensive Toxicology Database

- Receptor-mediated adverse pharmacologic/toxicologic effects not expected (new study)
- Toxicology studies of up to 2 years in mice and rats and 1 year in dogs showed no adverse histologic or biochemical effects on any organ system
- Exposure (AUC) of dogs to moxidectin in toxicology studies were 454-fold higher than after 2 doses of ProHeart 6 given 6 months apart (new study)
- No increase in tumors in 2-year carcinogenicity studies

## Pre-Approval ProHeart 6 Clinical Study Results

- Safety study results demonstrate
- Wide margin of safety
- Safe in breeding animals
- Safe in unique canine populations
- Ivermectin-sensitive
- Heartworm positive
- 100% efficacy at commercial dose
- 100% efficacy in large number (84) of breeds
- A total of 770 dogs were evaluated for US registration

- Pre-Approval ProHeart 6 Clinical Study Results

## Factors Limiting Heartworm Control in US Dogs

- Widespread availability of heartworm preventives has not changed the infection rates in last 10 years
- 240,000 dogs in US tested positive for heartworm nationwide in 2001
- One-fifth of surveyed dog owners stopped giving their dogs the monthly oral preventive altogether

## ProHeart 6 Approval

- Approved and marketed globally
- US – June 2001
- Canada, Japan, Italy, France, Spain, Portugal, Greece, Korea
- ProHeart SR 12
- Australia – October 2000
- 12 months heartworm protection
- 3 times ProHeart 6 dose

## ProHeart 6 Market Experience

- Rapid and broad acceptance by dog owners and veterinary professionals
- 24% US market share
- 47% Australian market share

## Brand Share Change2001 - 2004 Dispensed Units

- Source: *June 2004 Doane Market Research: Heartworm Tracking Study*

- Brand Share Change2001 - 2004 Dispensed Units

## ProHeart 12 - Australia

## US and Australian AER Reports

- 			_**US**_**	****	**_**Australia**_
- Doses sold		18,000,000		2,000,000
- AER rate	 		2.5 			1.6
- (per 10,000 doses)
- Allergy reporting rate			1.3 			0.8
- (per 10,000 doses)
- Death reporting rate			0.3 			0.1
- (per 10,000 doses)

## ProHeart 6 Introduction

- September 2004: FDAH voluntary recall of ProHeart 6 based on CVM concerns about adverse events
- Data reviewed by Canadian, Australian, European, and Japanese regulatory authorities
- Confirmed authority to continue marketing

## ProHeart 6 Epidemiological Evaluation(presented by Dr. Larry Glickman, Purdue University)

- Large independent nation-wide database:
- 	Banfield The Pet HospitalTM
- Nearly 7 million “encounters” (office visits)
- ProHeart 6, two heartworm preventives, vaccines were evaluated
- Results demonstrate no clinically significant increase in adverse events following ProHeart 6 treatment
- ProHeart 6 safety profile similar to 2 monthly heartworm preventives

- ProHeart 6 Epidemiological Evaluation(presented by Dr. Larry Glickman, Purdue University)

## Re-Evaluation of AERs by FDAH(presented by Dr. David Hustead, FDAH)

- Post-marketing monitoring of AERs
- Overall reporting rate is low
- Reporting rate is declining
- Most AERs appear to be allergic and self limiting
- Assignment of causality confounded by concurrent vaccinations
- Varied non-allergic AERs reflect diseases often seen in dogs

- Re-Evaluation of AERs by FDAH(presented by Dr. David Hustead, FDAH)