In 2013, many new products—in all areas of dermatology—were approved and launched, adding to the current index of available therapies and treatments. From recent approvals and extended indications to product launches, this article offers a look back at the year's news.
Earlier this month, Oculus Innovative Sciences, Inc. received a new FDA 510(k) clearance for its Microcyn Scar Management HydroGel for the management of old and new hypertrophic and keloid scars resulting from burns, general surgical procedures, and trauma wounds. In a 16-week study to demonstrate equivalency to a predicate device in scar management, patients with linear or widespread hypertrophic or keloid scars consistently were treated with Microcyn Scar Management HydroGel. Investigators evaluated the qualified scar using the Vancouver Scar Scale, which assesses scar vascularity, height/thickness, pliability and pigmentation. Pain and itch symptoms were evaluated by the subjects. In both the Microcyn HydroGel and the active control groups, the VSS total score improved consistently at each of the visits. At the end of treatment visit (Day 56), the mean VSS total score improvement from baseline was -2.10 in the Microcyn group, compared to -1.28 in the control group. At the end of the study visit (Day 112), the mean VSS total score improvement was -2.70 in the Microcyn group versus -1.83 in the control group. Individual signs and symptoms scores were evaluated throughout the study, which included improvement in itch and pain. The reductions from baseline in the mean individual signs and symptoms scores were greater in the Microcyn group. Oculus US dermatology partner, Quinnova Pharmaceuticals, intends to commercialize the product in the first half of 2014.
In November, the FDA approved Valeant Pharmaceuticals' Luzu (luliconazole) Cream 1% for the topical treatment of athlete's foot (interdigital tinea pedis), jock itch (tinea cruris), and ringworm (tinea corporis), caused by Trichophyton rubrum and Epidermophyton floccosum, in patients 18 years of age and older. Luzu is the first topical azole antifungal agent approved to treat tinea cruris and tinea corporis with a one-week, once-daily treatment regimen—all other approved treatments require two weeks of treatment. Interdigital tinea pedis is approved with a two-week, once-daily treatment. The FDA approval was based on positive results from three pivotal studies evaluating safety and efficacy of Luzu Cream 1% in patients with either tinea pedia or tinea cruris. For the two pivotal studies in tinea pedis with a treatment duration of two weeks, the primary endpoint was stringently defined as complete clearance four-weeks post-treatment. In the first study, 26 percent of patients treated with Luzu were completely cleared, compared to two percent of patients treated with vehicle. In the second study, 14 percent of patients treated with Luzu were completely cleared, compared to three percent of patients treated with vehicle. For the pivotal study in tinea cruris, complete clearance was assessed three-weeks post-treatment. After one week of treatment, 21 percent of patients treated with Luzu were completely cleared, compared to four percent of patients treated with vehicle. The company reported that the most common adverse events were mild application site reactions, reported in less than one percent of patients for both Luzu and vehicle.
In November, the FDA also approved BTG plc's Varithena (polidocanol injectable foam) for the treatment of patients with incompetent veins and visible varicosities of the great saphenous vein (GSV) system. Varithena (formerly known as Varisolve PEM) is a pharmaceutical-grade, low-nitrogen, polidocanol foam dispensed from a proprietary canister device. In two pivotal, placebo-controlled Phase III trials, VANISH-1 and VANISH-2, Varithena achieved a clinically meaningful improvement in the symptoms of superficial venous incompetence and the appearance of visible varicosities and addressed the underlying venous incompetence in the majority of patients treated. Current treatments for varicose veins include thermal ablation and surgery. Varithena provides US physicians with the only approved comprehensive therapy to improve symptoms and appearance for a wide range of varicose veins, including incompetent GSV, accessory saphenous veins and visible varicosities of the GSV system both above and below the knee. Treatment is a minimally invasive, non-surgical procedure that requires neither tumescent anesthesia nor sedation.
Actelion's Valchlor (mechlorethamine) received approval as the first and only FDA-approved topical formulation of mechlorethamine. Valchlor, a gel that is applied topically once a day, is an alkylating drug indicated to treat patients with stage IA and IB mycosis fungoides-type cutaneous T-cell lymphoma (MF-CTCL) who have received prior skin-directed therapy. Valchlor is an orphan drug that was acquired by Actelion US Holding Company, a subsidiary of Actelion Ltd., earlier this year as part of a merger with Ceptaris Therapeutics, Inc. Valchlor is distributed in the US by Accredo Specialty Pharmacy.
The FDA approved Juvéderm Voluma XC (Allergan), the first injectable filler approved to temporarily correct age-related volume loss in the cheek area in adults over the age of 21 in November. A pivotal clinical trial in the US and Canada demonstrated that Juvéderm Voluma XC was both a safe and effective treatment compared to the control group. Made with Allergan's proprietary VYCROSS technology, an advanced manufacturing process that results in a smooth gel that flows easily and consistently, Juvéderm Voluma XC helps create a more youthful appearance to the face and provides natural-looking results that last up to two years, according to the company. Additionally, Juvéderm Voluma XC contains a small amount of lidocaine, which helps numb the treatment area during the injection procedure. Vic Narurkar, MD, a clinical investigator on the Juvéderm Voluma XC trials, said the approval represents a significant step forward in the world of aesthetic injectable treatments for a number of reasons, explaining that while clinicians have known about the ability of fillers to volumize the mid-facial area for several years, all uses for this have been off-label until the approval of Juvéderm Voluma.
Obagi has renamed its Pro+Therapy line as Obagi Gentle Rejuvenation. Gentle Rejuvenation for sensitive skin features the exclusive, clinically proven ingredients Kinetin and Zeatin and patented Prosome delivery technology. The company offers a conversion chart to show the new product names at www.protherapymd.com/ConversionChart.pdf.
Botox Cosmetic (onabotulinumtoxinA, Allergan, Inc.) received FDA approval to temporarily treat moderate to severe lateral canthal lines—the first new aesthetic indication for Botox Cosmetic since it was approved in 2002 for the temporary treatment of glabellar lines in patients between the ages of 18 and 65 years. The safety and efficacy of Botox Cosmetic as a treatment for crow's feet lines were demonstrated in two randomized, multi-center, placebo-controlled clinical trials. Steven Dayan, MD, Clinical Assistant Professor at the University of Illinois and a clinical investigator in the Botox Cosmetic crow's feet clinical trials, believes the new indication is a significant development. “We can now tell patients that this is a treatment that has proven to be safe and effective through an enormous amount of research and trials that led to the stamp of FDA approval,” he explained. This comes with a certain level of comfort for both patients and physicians, according to Dr. Dayan.
The FDA recentnly granted 510(k) clearance for ResurFX, a new fractional non-ablative laser module from Lumenis. ResurFX is the latest application module for the M22 platform, expanding its capabilities to perform true fractional nonablative skin resurfacing. ResurFX uses a 1565nm fiber laser and a CoolScan scanner, which, according to Lumenis, enables a homogeneous and uniform pattern of coagulation columns, and requires only one pass. This feature saves practitioners' time and helps protect the patient's skin. The scanner also allows the user to choose from more than 600 combinations of shape, size, and density for optimal treatment and results. CoolScan uses a proprietary algorithm that places each fractional spot in a controlled, non-sequential manner allowing the tissue to relax between pulses and providing protection from overheating. The M22 platform combines three gold-standard technologies covering more than 30 indications in one system: intense pulsed light with optimal pulse technology, multispot Nd:YAG, and now the ResurFX for a complete aesthetic workstation.
Mitchel P. Goldman, MD, who reported in the September/ October 2013 issue of Modern Aesthetics® that he has used the M22 in his office for many years, said the new ResurFX module will increase the speed and efficiency of treatment by allowing him to treat more indications with the same device. For example, he says, patients can be treated with IPL first and then be treated with the ResurFX module to address scars or deeper wrinkles. “For what I call a ‘Five-Star Treatment,' I treat with low densities to the entire face and then treat areas of scarring or wrinkling by going up to a higher density and/or higher power over those areas,” Dr. Goldman explained.
VelaShape III, Syneron's new non-invasive body shaping platform, received FDA clearance and CE mark approval for temporary reduction in circumference of the abdomen. A clinical study of 42 patients showed results of an average abdominal circumference of 2.6 cm 10 weeks after a single treatment with the VelaShape III. The study also showed that 100 percent of patients responded to the single treatment protocol with an abdominal circumference reduction of at a least 1.5 cm in as little as two weeks. VelaShape III comes equipped with many new features designed to significantly reduce the number of treatments while reducing the percentage of non-responders. New features include increased radio-frequency power of up to 150W, real-time feedback mechanisms for consistent RF delivery independent of tissue variations, a built-in, real-time tissue surface temperature sensor, and a complete range of new tip configurations for various body locations.
Approved in late 2012, Nuvo Research and Galderma Pharma launched Pliaglis (lidocaine & tertacaine) 7%/7% topical anesthetic cream, designed to minimize pain during aesthetic dermatological procedures such as dermal filler injection, pulsed dye laser therapy, facial laser resurfacing, and laserassisted tattoo removal.
Pliaglis is a topical local anesthetic cream that forms a pliable peel on the skin when exposed to air. It comes as “a thick toothpaste-like paste that is applied in a thick layer to areas prior to injection or laser treatments,” explained Erin Gilbert, MD, PhD, in the May/June issue of Modern Aesthetics®. After 15-20 minutes, the dried paste can be peeled off in a single layer.
“Pliaglis is an alternative to any classical topical anesthetic used for cosmetic or medical dermatologic procedures. I find that its benefits are its consistency—it is easy to apply to focal areas—it doesn't leave a greasy film and patients find that it provides superior anesthesia,” Dr. Gilbert said, adding that she uses it for her own injections. She noted that the product can be slightly “crumbly” if removed too early and that phyicians should allow time for the product to dry adequately to ensure easy removal.
Dr. Gilbert reported that the product provides excellent pain inhibition. “Pliaglis is extraordinary for use on areas where the skin is thinner or is more intensely innervated such as the tear trough or the lips.”
The FDA cleared Vanquish from BTL Aesthetics for deep tissue heating for use in dermatologic and aesthetic procedures. According to the company, the device utilizes its Selective RFTM (radio frequency) to provide a non-invasive, operator-monitored, and contact-free approach to body treatment. Vanquish's technology emits an electromagnetic field over a large treatment area without the applicator panels making contact with the skin. Vanquish utilizes real-time tissue impedance tuning circuitry, like a radio tuner, to match the characteristics of RF energy with the particular response of the desired deep fat tissue layer. The advanced design of its Energy Flow Control engineering helps deploy the thermal effects of RF into the deep tissue while protecting the superficial skin layers and the deeper musculature. Vanquish is specially designed to treat the problematic midsection area with precise thermal energy that selectively affects the adipocytes in the deep tissue layer. In Vitro studies have demonstrated “apoptosis” or fat cell destruction. Multicenter clinical studies are underway in the US to validate optimal treatment protocols. Generally, four 30-minute sessions are scheduled one week apart over four to six weeks. Patients have shown lasting results up to six months or longer, when maintaining a healthy lifestyle of a smart diet and exercise regimen. According to Miles Graivier, MD, Vanquish offers several important and impressive features and benefits, including a non-invasive and nonsurgical contouring solution for body treatments, a large spot size, no consumables, and short, focused 30-minute sessions.
PSORIASIS AND PSORIATIC ARTHTRITIS
With recent FDA action on Janssen Biotech's Supplemental Biologics License Application (sBLA), Stelara (ustekinumab) is now approved for self-injection by patients.
The FDA also approved Stelara alone or in combination with methotrexate for the treatment of patients 18 years or older with active psoriatic arthritis (PsA). The approval was supported by findings from two pivotal Phase III trials (PSUMMIT I and PSUMMIT II). For the treatment of psoriatic arthritis, Stelara is administered as a 45mg subcutaneous injection at weeks zero an four, and then every 12 weeks, thereafter. For patients with co-existent moderate to severe plaque psoriasis weighing more than 220 lbs. (100 kg) the recommended dose is 90 mg subcutaneous injection at weeks zero and four, and then every 12 weeks, thereafter, according to Janssen Biotech.
Also approved recently for the treatment of adults with active psoriatic arthritis is UCB's Cimzia (certolizumab pegol). The approval was based on data from the RAPIDPsA study, an ongoing, Phase III trial designed to evaluate the efficacy and safety of certolizumab pegol in patients with active and progressive adult onset psoriatic arthritis. Patients treated with Cimzia 200mg every other week demonstrated greater reduction in radiographic progression compared with placebo-treated patients at Week 24. Treatment with Cimzia also resulted in improvement in skin manifestations in patients with PsA.
The new XTRAC Velocity 7 excimer laser from PhotoMedex is now available and offers more energy and greater efficiency than previous models. XTRAC delivers highly targeted UVB light to areas of the skin affected by psoriasis or vitiligo without harming the surrounding tissue. New features include an on-board computer system with enhanced patient tracking features, EHR compatibility, and the capacity to store clinical photographs. Streamlined calibration is also possible with the new device, which will be unveiled in practice this quarter. The Veolocity 7 also has a sleek, new profile that makes the system more compact than previous iterations.
LEO Pharma Inc. launched a patient-friendly 120g package size of Taclonex (calcipotriene and betamethasone dipropionate) Topical Suspension 0.005%/0.064% for the treatment of plaque psoriasis this year.
ACNE AND ROSACEA
The FDA recently approved Mirvaso The FDA recently approved Mirvaso (brimonidine) gel 0.33% for the topical treatment of the facial erythema of rosacea in adults 18 years of age or older. The approval was based on data collected from more than 550 patients enrolled in two Phase III clinical studies of one-month duration. The results of the studies showed that adults who used Mirvaso demonstrated significantly greater improvement in the facial redness of rosacea than vehicle gel. Data from two identically designed randomized, double-blind, vehicle controlled Phase III trials showed that Galderma's investigational topical brimonidine gel applied once-daily was significantly more efficacious than vehicle gel throughout 12 hours on days one, 15, and 29. The trials recruited subjects with moderate to severe erythema of rosacea, who were randomized to active treatment or vehicle control. Patients applied brimonidine 0.5% once-daily. Evaluations included the Clinician's Erythema Assessment and Patient's Self-Assessment. A long-term study in 276 patients who used Mirvaso for up to 12 months was also conducted. Mirvaso should be applied in a pea-sized amount, once daily to each of the five regions of the face: the forehead, chin, nose and each cheek. Applied once daily, Mirvaso works quickly to reduce the redness of rosacea and lasts up to 12 hours. Topical brimonidine tartrate gel 0.5% is safe and effective for the management of erythema of rosacea, with benefit evident as early as 30 minutes after application. In controlled clinical trials the most common adverse reactions (incidence ≥ 1%) included erythema, flushing, skin burning sensation, and contact dermatitis.
Joel Cohen, MD said he believes these studies exemplify what a good clinical trial should look like. “You can actually look at someone and show that over the course of the month they continue to respond similarly to the first couple days, and you start to see the effect within the first 30 minutes and it generally lasts up to 12 hours or so with some waning at that point,” he explained. He added that the long-term 52-week study showed that people not only respond for 4 weeks, they respond for 52 weeks similarly, showing there is no loss of efficacy of the medication.
Promius Pharma LLC launched Zenatane (isotretinoin), a newly FDA-approved AB rated equivalent to Accutane. With the launch of Zenatane, Promius also announced the start of its Promius Promise program, a pharmacy service designed to assist with patient education about treatment requirements and deliver Zenatane within 24 hours to US locations, at a reduced or no out-of-pocket expense and with shipping fees for eligible patients. Partnering with an accredited iPledge-certified US-based pharmacy, the program offers educational support for patients and assists with every aspect of iPledge program compliance. Excited about the prospects for the program, Richard G. Fried, MD, PhD told Practical Dermatology® that Promius Promise is a potentially emotion- and life-saving program that will bring important care to patients. In addition to preventing delay in therapeutic access and preventing patient drop out, Dr. Fried who pointed out that some patients who encounter any obstacle to access will simply drop out of treatment, said he believed the new program may also improve staff morale. Staff get bogged down daily with phone calls about generic substitution, non-formulary call-backs, and patients missing time windows for pregnancy testing—sometimes they can address issues directly, other times they need to schedule the patient for in-office appointments. The new program, theoretically, will remove this burden on staff and help improve access to care for patients.
The FDA extended the approval of Epiduo (adapalene 0.1%/ BPO 2.5%, Galderma) Gel to treat acne in children as young as nine-years-old. In a 12-week multicenter, randomized, vehicle-controlled, double-blind study, investigators evaluated the safety and efficacy of Epiduo Gel in 285 acne sufferers aged nine to 11 years. Results indicated that nearly 70 percent of parents with children in the Epiduo Gel treatment group saw improvement in their child's acne, compared to only 23 percent of parents with children on placebo. Common reported side effects included skin burning sensation, skin irritation, skin discomfort, dry skin, and erythema. Galderma also launced its new Epiduo TAP (Treatment, Adherence, and Performance) Program, an online and mobile patient platform that educates acne patients ages 13 and older about the proper application of Epiduo gel (adapalene 0.1% and benzoyl peroxide 2.5%) and encourages acne patients to stay adherent to treatment through an interactive and integrated performance-based platform. Through the program's incentive-based system, patients are coached to follow their daily skincare regimen via text and email reminders. These reminders may help patients stay more compliant with their treatment, which could improve treatment outcomes, and help prevent future breakouts.
After receiving FDA approval in May 2012, Stiefel launched Fabior (tazarotene) Foam in September 2013. Stiefel, a subsidiary of GlaxoSmithKline, said Fabior is the only retinoid in a topical foam formulation for acne vulgaris in patients aged 12 and older.
The FDA approved Naftin (naftifine HCl, Merz) Gel 2% for the treatment of interdigital-type tinea pedis. Naftin Gel 2% improves on the current formulation of Naftin Gel 1% by delivering the efficacy of naftifine hydochloride with a once-daily application treatment regimen, accodring to the company. In clinical studies, Naftin Gel 2% demonstrated continuous improvement in post-treatment efficacy rates for up to four weeks after the treatment regimen had ended. Naftin (naftifine HCl) Gel 2% improves on the current formulation of Naftin (naftifine HCl) Gel 1% by delivering the efficacy of naftifine hydochloride with a once-daily application treatment regimen. The approval of Naftin (naftifine HCl) Gel 2% was based on results from two pivotal US clinical trials involving 47 investigational sites and 1715 adult patients. The results indicate that patients treated with Naftin (naftifine HCl) Gel 2% experienced clinically significant cure rates when compared to placebo.
The FDA announced that it limited the use of Nizoral (ketoconazole) oral tablets, warning that the oral tablets can cause severe liver injuries and adrenal gland problems and advising that it can lead to harmful drug interactions with other medications. The FDA has approved label changes and added a new Medication Guide. As a result, Nizoral oral tablets should not be a first-line treatment for any fungal infection and only used for the treatment of certain endemic mycoses when alternative antifungal therapies are not available or tolerated. The FDA will continue to evaluate the safety of Nizoral tablets.
The FDA approved two new drugs for metastatic or inoperable melanoma— dabrafenib (Tafinlar) and trametinib (Mekinist). Dabrafenib is an inhibitor of the BRAF gene when it carries the so-called V600E mutation. Trametinib inhibits a target known as MEK and is effective primarily against melanomas carrying either the V600E or V600K mutations. Dabrafenib and trametinib were approved separately as stand-alone drugs, not as a combination, although therapy with both drugs together has been tested clinically and appeared to be better than dabrafenib alone.
The agency also approved a companion diagnostic test for both agents to detect certain mutations in the BRAF gene that render melanoma cells susceptible to the drugs. A new diagnostic product, the THxID BRAF test, was evaluated in the same clinical trials supporting the two drugs' approvals and was used to select patients for the trials.
GlaxoSmithKline manufactures the agents. The BRAF mutation test is sold by bioMerieux.
Recently, the FDA has granted priority review designation to GlaxoSmithKline's supplemental New Drug Applications (sNDAs) for combined use of Tafinlar (dabrafenib) and Mekinist (trametinib) for the treatment of adult patients with unresectable or metastatic melanoma with a BRAF V600 E or K mutation. The applications are based on data from a randomized Phase I/II study comparing combination therapy with dabrafenib and trametinib to dabrafenib monotherapy in adult patients with BRAF V600E and V600K mutation positive metastatic melanoma.
Caliber Imaging & Diagnostics, formerly Lucid, Inc., introduced its VivaScope 1500 Multilaser system, cellular imaging devices that give researchers the option of a painless, noninvasive optical skin biopsy to study changes at the cellular level.
The new VivaScope 1500 Multilaser systems include three lasers of different wavelengths that can be used in fluorescence-mode imaging to enhance image contrast when combined with dyes that are FDA-approved for human use.
According to Babar Rao, MD, Vivascope provides skin images with cellular details comparable to conventional histology. While conventional histology is still the gold standard for histological diagnosis, Dr. Rao explained that the downside is that it requires anesthesia, cutting, and, in some cases, stitching, which can result in pain, discomfort, and unnecessary scars in the event of a benign diagnosis. “With confocal microscopy, a clinician can instantly view skin lesions and make a treatment decision in a few minutes, without waiting for conventional specimen processing and a biopsy report,” he explained.
Dr. Rao says one of the best uses of this technology in his practice is on moles on children. “Most moles on children are benign, and a biopsy would result in unnecessary discomfort for the child, and the Vivascope provides painless diagnosis. The other side of that coin is that you can have child with a mole that really should be investigated, and the parents are apprehensive about allowing the child to have a biopsy, especially on the face. In that case we can diagnose a rare malignant lesion on a child that might otherwise have gone unchecked,” he said. “Similarly, adult patients are often apprehensive about, such as the face, neck, and décolleté.”
It can also be used for adult patients who are apprehensive about biopsying lesions on aesthetically important sites on themselves or for patients who have numerous moles (as in hundreds), where many of them look atypical but are usually proven benign with a biopsy. “We can rule out benign diagnoses with the Vivascope, and monitor them if necessary,” he said.
“One of my personal favorite aspects of the Vivascope is using it to maximize the efficiency of the patient's treatment. If the lesion looks suspicious enough to be biopsied, the typical protocol is to first biopsy, and then if it is malignant, the patient must return for an excision,” he explained. “However, if the lesion looks suspicious on the Vivascope, we can excise it right away, which saves the patient an unnecessary biopsy and an extra trip to the doctors office, and saves the healthcare system the cost of another visit and another procedure.”