F40 FOR THE TREATMENT OF FACIAL WRINKLES & SCARS
Injectable soft tissue fillers are least-invasive aesthetic medical class III devices used to correct wrinkles, acne scars and traumatic scars, add volume to areas of the face and hands to achieve a fuller, smoother and more youthful appearance, and to enhance facial contours such as the nose, cheeks, temples, and chin.
Dermal fillers are among the most popular aesthetic procedures because they deliver immediate results in an outpatient setting (20-30-minute procedure), are affordable, bear few risks (mostly slight swelling and bruising, which subside within 24-48 hours), and require little to no recovery time.
In 1981, bovine collagen (Zyderm® I) became the first FDA-approved injectable dermal filler and created a new aesthetic procedure category of injectable wrinkle treatments known as “fillers”. Because bovine collagen injections lasted only for about 4 months, innovative personal aesthetics companies have since created longer-lasting and permanent fillers to increase patient satisfaction.
Today, dermal fillers are classified as temporary, longer-lasting, and permanent implants according to their varying effectiveness. All of today’s most widely used fillers were developed during the past two decades and are distributed by healthcare companies Allergan, Nestle´/Galderma, Valeant Pharmaceuticals, Laboratories Teoxane, Merz Pharma, and Suneva Medical.
|ArteFill® (BellaFill®)||PMMA/Collagen/Lidocaine||Permanent||>60 months||Suneva Medical|
|Radiesse®||Hydroxylapatite||Longer-lasting||9 months||Merz Pharma|
|Juvederm® XC Ultra and Ultra Plus||Hyaluronic Acid||Temporary||Ultra 3-6 months, Plus 6 months||Allergan|
|Restylane®||Hyaluronic Acid/Lidocaine||Temporary||3-6 months||Galderma/Valeant|
|Belotero®||Hyaluronic Acid||Temporary||6 months||Merz Pharma|
|Juvederm® Voluma XC VOLUMIZER||Hyaluronic Acid/Lidocaine||Longer-lasting||9-12 months||Allergan|
|Sculptra® VOLUMIZER||Poly-L-Lactic Acid||Longer-lasting||9 months||Galderma|
In 2015, cosmetic procedures increased by 39% over the past 5 years and Americans spent more than $13.5 billion on combined surgical and non-surgical procedures. Non-surgical procedures accounted for 85% of all cosmetic procedures and 42% of total expenditures(22). Non-surgical procedures increased by 22% over 2014 with 10,879,909 procedures performed, with injectable hyaluronic acid fillers showing a 27% increase in 2015. Injectables continued to dominate aesthetic procedures in 2015, where the #1 and #2 non-surgical procedures were Botulinum Toxin (4,267,038) and Hyaluronic Acid (2,148,326) wrinkle injections. Overall, injectable wrinkle procedures have experienced an increase of 1,900% since 1997 and continue their steep upward trend:
In addition, more men continue to seek out aesthetic procedures with 622,000 injectable wrinkle procedures performed on men in 2015, or roughly 10% of total wrinkle injections (a 30% increase since 2011).
Decades of facial expressions, bone atrophy of the facial skeleton, as well as genetic (intrinsic) and extrinsic factors such as smoking and sun exposure, lead to ‘facial aging’ by way of wrinkles and deflation (hollowness). Therefore, dermal filler indications are primarily the ‘aging face’ with its increasing wrinkles and folds, as well as its slow fatty volume loss and apparent indentations.
Even though the thickness of the facial dermis does not diminish over time (in contrast to the skin on the extremities), the dermis loses its elasticity (loss of collagen and elastin) and the subdermal fatty layer diminishes and sags due to gravity.
Most fillers have two functions: a “volumizing” one, restoring volume to the face, and a “filling” one, leveling deep wrinkles and folds (as opposed to botulinum toxin (e.g. Botox®), which is used to paralyze underlying facial muscles in the quest to smooth out forehead wrinkles.)
The purpose of permanent fillers is to provide patients and physicians a safe and effective alternative to temporary and semi-permanent fillers to reduce risks associated with repeat injections such as swelling, bruising, scarring, uneven and/or inconsistent correction, provide patients an economic benefit over time, and obviate the need for repeat office visits and treatments (time, cost, inconvenience, and discomfort).(25)
As the popularity of wrinkle injections continues to rapidly increase, so do injection fatigue and credit card fatigue experienced by patients with temporary products that have to be re-injected every 4-6 months.
However, many patients initially prefer temporary fillers to experience the results of wrinkle/scar correction, and subsequently choose a longer-lasting or permanent product to obviate the need for repeat injections.
In order to address this concern, our core management team created the first and only U.S. FDA-approved permanent injectable wrinkle filler ArteFill® in 2006 (now Bellafill® marketed by Suneva Medical):
Third-generation product ArteFill® has been marketed in the U.S. since 2007, and subsequently also in Canada, South Korea and Singapore (Suneva Medical). Its predecessor, second-generation product Artecoll® (not U.S. FDA-approved), has been marketed in China since 2002 (Hafod Bioscience B.V.).
ArteFill’s excellent 10-year safety and efficacy profile in the United States has encouraged us to create F40, the next-generation (4th-generation) permanent injectable wrinkle filler for the U.S. and international markets.
Enduring results after PMMA/collagen injections (U.S. clinical trials):
Traumatic scar correction with PMMA/collagen injection (ex-US):
Acne scar treatment with PMMA/collagen injections (ex-US):
Rhinoplasty with PMMA/collagen injection (ex-US):
Treatment of radial lip lines (smoker lines), smile lines and vermillion border of lips with PMMA/collagen injections (ex-US):
Once approved for clinical use, F40 will be a 4th-generation permanent dermal filler. Our proprietary injectable polymethylmethacrylate (PMMA) microsphere technology platform has undergone over 25 years of product evolution and has been used in millions of patients worldwide since 1989 with earlier-generation products. In 2006, third-generation ArteFill® (now Bellafill® marketed by Suneva Medical), became the first and only FDA-approved permanent injectable wrinkle filler for the treatment of nasolabial folds or smile lines. In 2013, ArteFill (Bellafill) also became the first and only injectable filler to obtain FDA-approval for the treatment of acne scars.
Our research & development efforts since inception of the Company have partly focused on the progressive improvement of PMMA microsphere quality, as well as the collagen carrier they are suspended in for injection. We have developed a new and proprietary process to produce our microspheres to the highest quality standard as set forth by the U.S. FDA and enhanced the quality of our collagen carrier material.
A narrow size distribution and overall microsphere conformity in regards to roundness, smoothness and shape are of critical importance to reduce the risk of adverse effects such as foreign body reactions. In order to minimize or eliminate any potential side effects, it has been our goal to meet or exceed FDA’s stringent quality requirements in all our products.
Quality Evolution of PMMA Microspheres:
Worldwide ex-U.S. (CE-mark)
U.S. FDA Approval of ArteFill®
< 1% of PMMA "by the number" is <20 microns
2016 - U.S.
2016 - U.S.
In regards to our collagen carrier, we strive to incorporate the highest quality bovine collagen sourced from a closed U.S. cattle herd in all of our products to ensure patient safety, even microsphere suspension at room and body temperature, as well as a perfectly uniform distribution in soft tissues after injection to maximize augmentation results.