With a growing patient base spanning Millennials to Baby Boomers,combined with the introduction of novel products and cutting-edge techniques, facial injectable treatments remain in high demand.
In the realm of neurotoxins, for nearly a decade physicians have had three options available: Botox® Cosmetic (Allergan), XEOMIN® (Merz Aesthetics), and Dysport®(Nestle Skin Health / Galderma), which currently celebrates its 10-year anniversary of treating glabellar lines.
As clinical literature comparing BoNT-A agents for antibody formation, resistance and loss of effect is inadequate, a recent study analyzed Botox Cosmetic, Dysport and XEOMIN for decreased therapeutic effect based on data from the FDA adverse event reporting system (FAERS) database. The study revealed that adverse events for XEOMIN, which has been shown to be the only BoNT-A agent on the U.S. market that has removed unnecessary proteins and maintains a very pure active component, were much less likely to be related to decreased therapeutic effect versus the other two products.
Looking ahead, two products in the pipeline are expected to expand practitioners’ options and shake things up in the neurotoxin market. The recently FDA-approved product, Jeuveau™, from Evolus (Newport Beach, Calif.), will provide the first 900 kDa botulinum toxin since Botox Cosmetic. A 2019 launch of Jeuveau in the U.S. and Canada is imminent. A European release is scheduled for 2020.
Leading up to FDA approval, Evolus effectively completed a five-study clinical trial in the U.S., the E.U. and Canada in order to receive regulatory approvals for the treatment of moderate to severe glabellar lines. The clinical program, which met the respective primary endpoints, included three multi-center, randomized, controlled, single dose Phase III studies and two open label, multiple dose, long-term Phase II studies.
In April, the company announced the publication of the largest European and Canadian Phase III head-to-head pivotal non-inferiority study comparing Jeuveau and Botox Cosmetic. Results showed responder rates for the primary endpoint of 87.2% for Jeuveau and 82.8% for Botox.
Jeuveau’s planned price point – as much as 20% to 25% lower than the cost of Botox – will likely create strong competition with the big three neurotoxin providers. This fierce competition for market share will ultimately benefit physicians and consumers.
Another new product, known as RT002, from Revance (Newark, Calif.), or Daxi, has shown potential of becoming the first long-lasting injectable formulation of botulinum toxin type A.
In addition, partnering with South Korea-based neurotoxin developer Hugel, Inc., Croma-Pharma GmbH (Leobendorf, Austria), is poised to enter the U.S. market in the near future with Botulax and its range of saypha® hyaluronic acid (HA)-based fillers and PDO thread products.
Whatever novel or established products are being used, practitioners are busily investigating new approaches that employ neurotoxins, dermal fillers, platelet-rich plasma (PRP), stem cells and other biologics alone or in combination, in order to advance rejuvenative therapies and procedures.
When it comes to dermal fillers, “Physicians are using a few new techniques, most of which are coming to the U.S. from Europe,” stated Lori Robertson, MSN, FNP-C, clinical director and owner of Skin Perfect Medical in Brea, Calif.
“For instance, skin boosters use injectable HA to restore a smooth complexion and stimulate collagen production. You employ micro droplets that help plump up the skin and kind of lift it up, but also pull water into the area. This will help boost hydration. Also, these products provide a really good way to help soften wrinkles when toxins alone won’t do it.
”Other new approaches include the “ferning” technique developed by Amsterdam-based Tom Van Eijk, MD, noted Ms. Robertson. “This injection technique uses only minimal amounts of Restylane® Classic (Galderma / Nestle Skin Health) to actually strengthen the skin and cause collagen growth with dermal thickening over time. The results are astounding,” she said.
As reported by Haideh Hirmand, MD, a plastic surgeon in New York City, N.Y., “Consumers are always asking for a natural looking result, and providers have responded, especially when it comes to fillers.
”The most natural appearing fillers allow movement with the contour of the face. Galderma’s Restylane® Refyne and Restylane® Defyne are HA-based fillers that utilize a special technology, which allows the injected filler to move with a range of facial expressions. The products help smooth moderate lines with built-in flexibility, providing a consistent texture for natural expressions in motion.
“These products are designed to help smooth out smile and laugh lines while maintaining a natural look, thereby creating a beautiful effect without any visible signs of having had any treatment when you smile and show expression,” Ms. Robertson noted. “Defyne is my ‘desert island’ filler because I can do so much with it. It doesn’t sit there and lift. It will diffuse and fill.”
Another innovative use of fillers and neurotoxins encom-passes bio-stimulation, which is the triggering of the body’s self-healing mechanisms, in addition to forms of regenerative medicine, which in some cases apply the patient’s own tissue alongside injectable therapies.
As a concept, bio-stimulation is often used with terms like “collagen induction therapy” and “collagen restoration,” which covers an expansive list of products and technologies from injectables to microneedling.
Among fillers, products not only include HA, but also straight collagen, calcium hydroxylapatite (Radiesse; Merz Aesthetics) and injectable poly-L-lactic acid (PLLA), found in the Sculptra filler. Fillers comprising Polycaprolactone (PCL), such as Ellansé from Sinclair Pharma, offer high viscosity bio-stimulation.
Combining these therapeutic approaches is becoming more popular, noted Dr. Hirmand. We are discovering ways to remodel the skin using collagen induction therapies with fillers, to bio-stimulate rather than just fill lines,” she expressed.
“We have protocols that optimize the collagen induction and bio-regenerative properties of fillers, which are like skin boosting techniques versus just filling one-off lines and hollows. It is a way to use HA to extend its utility beyond volumization,” Dr. Hirmand continued.
The clinical work being done by physicians to exploit the bio-regenerative qualities of injectables is truly cutting-edge, Dr. Hirmand stated.
“We are a little bit ahead of the science,” she elaborated. “The use of injectables in bio-regenerative aesthetic therapies, whether it is HA, PRP or stem cell therapies, is producing anti-inflammatory effects that we are seeing in clinical settings. The science is going to be emerging over the next few decades to support that.”
One of those novel, but lesser known, approaches is micro-beading, which employs fillers to address a specific problem related to blepharoplasty, in which a hollowness around the eye gradually becomes more pronounced, post-procedure.
According to Dr. Hirmand, who developed this technique, “Microbeading is a very advanced technique that uses fillers in a new way, to inject into the lower lid itself. The idea is to not place filler under the thin skin of the lower lid, but instead to actually put it under the reticularis.”
“As people age, one of the changes that we observe, whether or not they had surgery or never had herniation of the fat bag, the eye starts to look really set back and the lower eyelid sometimes start to look hollow,” Dr. Hirmand pointed out.
“Further rejuvenation treatments actually exacerbate that hollowness in the lower lid. I started using custom blunt cannulas for periorbital injections and saw they were working. I’ve combined it many times with tear trough injections, but note that not everybody is a candidate. Also, it is not something that all physicians can use, like micro Botox. It is a very tricky, high level procedure.
”The more commonplace micro Botox procedure involves the injection of microdroplets of diluted botulinum toxin into the dermis or the interface between the dermis and the superficial layer of facial muscles. This results in decreased sweat and sebaceous gland activity that can improve skin texture and treat fine lines and wrinkles. It has also been used to address acne and rosacea.
“The micro Botox type treatment is effective, but it is very temporary. It has been around for years, but has recently made a slight comeback, and is something that practitioners can promote,” Ms. Robertson indicated. “However, you can’t control the neurotoxin like you really want to in certain situations, though. It is similar to when physicians blend PRP with fillers and find it doesn’t work that well.”
A more popular method combines PRP with RF microneedling, which has been shown to tighten and lift skin, as well as address fine lines, wrinkles, large pores, stretch marks and acne scarring. The heat generated by RF energy produces a healing response that allows the skin to thicken and tighten. The accompanying PRP, which is taken from the patient’s blood, releases growth factors and other cytokines to promote healing while also attracting the body’s stem cells to repair the damaged tissue.
In a short time, PRP has materialized into a popular but little understood transport agent for various products. The use of PRP involves hardware that processes the patient’s blood. For instance, RegenLab® USA (New York City, N.Y.) offers a point-of-care, one-step closed PRP preparation system that boasts optimal platelet recovery of more than 80%, an efficient 1.6x concentration factor, as well as sterile, biocompatible, non-pyrogenic and disposable components.
Healeon Medical, Inc. (Newbury Park, Calif.) recently released its High-Density Platelet-Rich Plasma Series, which is also designed for point-of-care treatments and provides a variety of options, concentrations and volumes in PRP production.
An emerging injectable approach takes facial rejuvenation to a new level. Renuva from MTF Biologics (Edison, N.J.) is an injectable extracellular matrix that contains the collagen, growth factors and proteins needed for vascularization after injection, where it acts as a scaffold that literally grows new fat cells.
“It is basically an injectable adipose matrix,” said Dr. Hirmand. “I can take a syringe and literally inject something that can grow fat in the body, using a person’s own regenerative capabilities. This is the ultimate bioregenerative product."
In a slightly different vein, Biologica Technologies® (Carlsbad, Calif.), offers Allofill®, an adipose-derived injectable filler containing naturally occurring growth factors, and AMP aesthetic™, an off-the-shelf alternative to PRP.
Considering the future direction of these types of aesthetic treatments, which are more regenerative in nature, it is no surprise that younger generation patients, in particular, are interested in them as part of a preventive anti-aging regimen.
“Millennials are pushing the whole industry forward,” stated Rand Rusher, RN, a Beverly Hills, Calif.-based injector and injection trainer. “I like to be very cautious about that word ‘prevention’ and starting treatment on young patients. ‘Prevention' is not really a word that we should use in this community. To say that you are ‘preventing’ means you are guaranteeing that your patient is not going to grow old, and you can’t say that.
“Moreover, if you are putting a neurotoxin into a 20-some-thing’s levator muscle, and you do that for the next 20 years, then let them know they better save their money for a brow lift, because although the levator muscle weakens on its own, the depressor does not,” Mr. Rusher continued. “My point is that you need to be careful about educating your younger clientele on the effects of neurotoxin.”