Safety and Efficacy Data

OVERVIEW

Artefill® is a safe and effective dermal filler for the correction of nasolabial folds or smile lines.

Many clinical trials have been conducted leading up to and following FDA approval in October 2006. A prospective 5-year study of 1,000 patients is currently being conducted by 23 institutions to evaluate the long term safety of Artefill. And additional clinical studies are planned to further validate Artefill’s safety and effectiveness.

Clinical Trial Highlights:

Prior to FDA approval, two clinical studies were conducted in the United States to demonstrate the safety and effectiveness of Artefill. One study was primarily focused on determining Artefill’s safety. The second study was to determine both safety and effectiveness.

Clinical Study #1. In this safety study, both the doctors and patients knew that Artefill was being injected. This multi-center study reviewed the safety of Artefill injections for the correction of facial wrinkles. 157 patients were enrolled and monitored at 3, 6, and 12 months after treatment. 126 out of the 157 patients (80%) completed the 1-year study. The safety data from this study was combined with the safety data from the controlled study to define the safety record for Artefill.

Clinical Study #2. A controlled multi-centered study of 251 patients conducted at 8 research clinics compared the safety and efficacy of Artefill and a commercially available collagen implant for the treatment of facial wrinkles. The patients were randomly divided into two groups with 128 patients receiving Artefill and 123 receiving collagen injections. After 6 months, the effect of Artefill was compared to the collagen patients who served as the control group. Photographs were taken of all of the treated wrinkles at each office visit and evaluated by a separate group of doctors who were not involved in treating the patients. These doctors evaluated the coded photographs using a standardized rating scale to grade the effectiveness of both the Artefill and control collagen results. Safety was evaluated by comparing the number and severity of side effects during and for 12 months after treatment.

Throughout the clinical trial, there was no significant difference in the safety profiles of Artefill and the collagen control. Artefill-related adverse events occurred infrequently and were primarily of mild intensity. Patients were evaluated one year after treatment and demonstrated minimal transient side effects.

No Severe Adverse Events Reported with Artefill in the U.S. Pivotal Clinical Trial

	Artefill (n=128)				Collagen Control (n=123)
Type of Events	Mild	Moderate	Severe	TOTAL	Mild	Moderate	Severe	TOTAL
Events localized to injection site+	18(1*)	4	-	22	13(2*)	12	8	33
Granuloma and/or enlargement of implant++	-	-	-	-	-	-	1	1
Systemic events**	1	3(1*)	-	4	1(1*)	-	-	1
Severe illness, trauma, death	-	-	-	-	-	-	1(1*)	1
TOTAL AEs	19	7	0	26	14	12	10	36

* The number outside the parentheses are the Total AEs, the number within the parentheses are the subset within the Total that are deemed NOT related to the implant by the investigator
+ This includes two reactions recorded as AEs that also required “removal or drainage”; one Artefill AE(mild) treated by removal where pathology showed no foreign body reaction and one collagen AE(severe) treated by incision & drainage, no pathology available
++ This includes one collagen AE(severe) which required “removal or drainage”; treated by incision & drainage, no pathology available
** Blurred vision, recurrence of existing herpes labialis, flu-like symptoms, other systemic complications

Five-Year Prospective Study

A prospective study of 1,000 Artefill patients is being conducted by 23 institutions. The study was initiated in October 2007 and is now completely enrolled. The five-year study is being conducted to follow the long term safety of Artefill for the correction of nasolabial folds.