ArteFill®

ArteFill® is the First FDA-Approved Non-Resorbable Aesthetic Injectable Implant for the Correction of Nasolabial Folds

ArteFill is a unique combination of homogeneous precision-filtered microspheres suspended in a solution of purified collagen gel and 0.3% lidocaine to alleviate discomfort during injection. ArteFill is manufactured in our dedicated 35,000 sq ft current good manufacturing practices (cGMP) compliant manufacturing facility and corporate headquarters in San Diego. The facility has been determined to be in compliance with both the FDA's Quality System Regulations and ISO 13485.
In October 2006, ArteFill received final approval from the FDA, making it the first and only non-resorbable aesthetic injectable implant to gain FDA approval.

Masked Observer Ratings of Nasolabial Fold Improvement
When ArteFill is injected into the skin underneath a wrinkle, the microscopic spheres remain intact at the injection site and provide a structure to support the wrinkle and help prevent further wrinkling. The body's naturally produced collagen replaces the injected bovine collagen within 3 to 6 months and encapsulates each individual microsphere to achieve a long-lasting wrinkle correction. In our U.S. clinical trials, patients receiving ArteFill showed significant improvement in the correction of nasolabial folds compared with patients receiving a collagen control treatment. The ArteFill group had fewer adverse events reported than the control group, but the difference was not considered significant.

What is a Wrinkle?
Human skin is composed of 2 layers, the epidermis (outer layer) and the dermis (inner layer). Superficial wrinkles and slight pigmentation problems generally originate in the epidermis. Deep wrinkles and scars involve the dermis. Collagen and elastin comprise the structural matrix of the skin and are secreted by fibroblast cells in the dermis. These secreted substances are critical in maintaining the structure of your skin. In young and healthy individuals, there is sufficient collagen and elastin produced; however, as individuals get older, less collagen and elastin are secreted, which leads to a weakening of the structural matrix of the skin and loss of elasticity. The skin becomes thinner and loses fat so it looks less plump and smooth. In deep facial folds or wrinkles, the thickness of the skin is diminished to approximately one-third that of the surrounding skin. While all these changes are taking place, gravity is also at work pulling at the skin and causing it to sag over time. At this stage, surgical tightening of the skin (face lift) is the rejuvenation procedure of choice, which is frequently combined with an injection wrinkle filling procedure.

ArteFill® U.S. Clinical Trial Results
ArteFill was evaluated in a prospective, multicenter, controlled, randomized, double-blind clinical study in which subjects received either ArteFill or a commercially available collagen implant control (Zyplast®) for the treatment of soft tissue defects of the face. A total of 251 subjects (128 ArteFill, 123 control) were treated at 8 dermatology or plastic surgery centers in the U.S. Follow-up periods for both safety and efficacy were at 1, 3, and 6 months, with a final 12-month safety evaluation. The efficacy data, measured by masked observers using a photographic Facial Fold Assessment (FFA) Scale, demonstrated a significant improvement with ArteFill compared with collagen at 6 months (p<0.001). At 6 months, the investigator success ratings and the subject satisfaction ratings were superior for ArteFill (p<0.001). In the ArteFill group, 12-month follow-up was obtained for 111 subjects (86.7%) and showed persistence of significant correction. ArteFill treatments showed fewer adverse events compared to treatments administered to the control group, although the difference was not statistically significant.
In October 2006, ArteFill received final approval from the FDA, making it the first Permanent Aesthetic Injectable Implant™ for the correction of smile lines, or nasolabial folds.

ArteFill Is Different From Dermal Fillers

How does ArteFill work?
ArteFill is a unique dual-acting permanent aesthetic injectable implant that provides both immediate and enduring cosmetic benefits. First, ArteFill visibly corrects the smile line by providing volume beneath the wrinkle, similar to other dermal fillers. Unlike temporary dermal fillers, ArteFill contains microspheres that provide the permanent support structure required to sustain the wrinkle correction. The microspheres are made of polymethylmethacrylate (PMMA), one of the most widely used synthetic implant materials in medicine. Studies have shown that PMMA microspheres are both biocompatible and safe for use as soft tissue fillers. Since macrophages and human enzymes are unable to break down PMMA, the microspheres are not degraded or absorbed by the body. The microspheres are 30 to 50 microns in diameter, barely visible to the naked eye, and are suspended in a purified bovine collagen carrier gel. Once injected, the microspheres reside permanently at the injection site for persistent wrinkle correction.

How is ArteFill different from BOTOX® Cosmetic and temporary dermal fillers?
BOTOX Cosmetic (e.g., botulinum toxin) is a temporary muscle-paralyzing drug, not a dermal filler. Botox™ Cosmetic is injected directly into the target muscle to block the nerve signals from the brain to the muscles so that they cannot contract. Wrinkles then gradually become smoother due to disuse. The effects last for approximately three to four months. Temporary dermal fillers are made of different kinds of natural or synthetic materials that have been developed over the years for injection into the skin. The materials in these products are completely metabolized and absorbed by the body over time. As a result, the aesthetic benefits of these temporary dermal fillers decrease over time, and generally last up to six months. Unlike Botox™ and existing temporary dermal fillers, ArteFill contains microspheres made of PMMA. These microspheres are not absorbed or degraded by the human body. Following injection, the PMMA microspheres in ArteFill remain intact at the injection site and provide a permanent structure to support the wrinkle and help prevent further wrinkling. As a result, we believe that ArteFill will provide patients with aesthetic benefits that may last for years. This innovative technology platform has created a new category of aesthetic injectable product known as Permanent Aesthetic Injectable Implant™.

ArteFill Safety Features

• Precision-filtered, suspended, PMMA microspheres optimized over 3 generations

• Purified bovine collagen gel

• Collagen source is a closed herd in the U.S. (FDA-compliant)

• Proprietary, non-porous syringes contain 0.8 cc and 0.4 cc ArteFill

• Optimized injection flow characteristics

• Pharmaceutical-grade product manufactured in a fully dedicated cGMP facility in San Diego, California

• Company-sponsored ArteFill Physician Training Program

A Word About Artecoll®
Artecoll is manufactured and distributed by unrelated companies located in The Netherlands. Artes Medical has never manufactured or distributed Artecoll. In 2004, we acquired all worldwide intellectual property rights related to Artecoll and ArteFill and a facility to produce PMMA microspheres in Frankfurt/Main, Germany.
Following our acquisition of this technology, we developed a new product called ArteFill. We have made further refinements to the PMMA manufacturing process that we believe improve the characteristics and purity of the PMMA microspheres. In addition, to meet the FDA’s requirements, we have established our own dedicated QSR-compliant manufacturing facility in San Diego, California to produce the bovine collagen used in ArteFill and to complete the manufacturing, packaging, and labeling processes for ArteFill.