Approvals of Note From 2016
A look back at FDA approvals in dermatology from the year.
From aesthetics to clinical dermatology, many new products were approved and launched in 2016, adding to the current index of available therapies and treatments. For updated coverage of approvals in dermatology, visit dermwire.com.
The FDA approved two new products for the treatment of nasolabial folds (NLF) or “laugh lines,” in patients over the age of 21—Galderma's Restylane Refyne and Restylane Defyne. Restylane Refyne was approved for the treatment of moderate to severe facial wrinkles and folds and Restylane Defyne for the treatment of moderate to severe, deep facial wrinkles and folds. Both products are manufactured with XpresHAn Technology, creating gels that offer a range of flexibility and support for varied patient needs. Restylane Refyne and Restylane Defyne have been shown to maintain effectiveness for the treatment of laugh lines for up to 12 months.
Syneron Candela received FDA 510(k) clearance for Profound when using the SubQ handpiece and cartridge to improve the appearance of cellulite in patients with Fitzpatrick skin types I-III, as supported by long-term data. A multi-center clinical study of Profound showed improvement of cellulite severity (in dimples and/undulation irregularities) in 94 percet of treated thighs assessed at a three month follow up by blinded review. Sustained improvement was observed at six month follow up in 93 percent of the treated thighs. When considering improvement in each cellulite feature separately, 86 percent of the treated thighs (of the 80 thighs with dimples at baseline) showed improvement in dimples, and 76 percent of the thighs (all thighs had undulation at baseline) showed improvement in undulation irregularities.
A recently launched off-the-shelf fat-derived filler may provide the long-lasting results associated with fat grafting plus the convenience of other ready-to-use injectables. Allofill, Biologica Technologies’ first foray into aesthetics, launched in late September. Allofill is a ready-to-use, allograft-derived filler retains the native extracellular matrix (ECM) components of allograft-derived adipose tissue and over time will be remodeled into a patient's own soft tissue.
The FDA awarded BTL Aesthetics a new designation for it non-invasive fat reduction treatment, BTL Vanquish ME—the treatment is now FDA-cleared for the circumferential reduction of the abdomen and thighs. The clearance was secured following several rounds of clinical testing to provide ample evidence of its efficacy and safety—which has also been previously documented thanks to two studies published in peer-reviewed journals.
This past summer, the FDA re-issued a warning about the dangers of mercury in skin creams, beauty and antiseptic soaps, and lotions. In the past few years, the FDA and state health officials have discovered numerous products that contain mercury, and there have been cases in which people exposed to such products have had mercury poisoning or elevated levels of mercury in their bodies. The FDA does not allow mercury in drugs or in cosmetics, except under very specific conditions where there are no other safe and effective preservatives available – conditions that these beauty products do not meet. The FDA suggests checking the label to see if the words “mercurous chloride,” “calomel,” “mercuric,” “mercurio,” or “mercury” are listed. If the product contains these ingredients, avoid it. The products are usually marketed as skin lighteners and anti-aging treatments. Adolescents may use these products as acne treatments.
If the ingredients aren’t listed and there is no product label, don’t assume it’s fine, the FDA warns. Federal law requires that ingredients be listed on the label of any cosmetic or nonprescription drug. In addition, don’t use drugs or cosmetics labeled in languages other than English unless English labeling is also provided. That’s also a sign that the product may be marketed illegally. Sellers and distributors who market mercury-containing skin whitening or lightening creams in the U.S. may be subject to enforcement action, including seizure of products, injunctions, and, in some situations, criminal prosecution.
The FDA cleared Syneron Medical Ltd.’s PicoWay picosecond laser for a new ultra-short 785nm wavelength. The addition of the new wavelength expands the capabilities of the PicoWay picosecond laser, making it possible to remove all tattoo ink colors including blue and green. The clearance of the new third wavelength was supported by a 15 patient study, covering 22 tattoos, of which 18 contained blue and green inks. Blinded evaluation of tattoo clearance, by independent board-certified physicians, showed that 83 percent of the treated blue/green tattoos had "good" to "complete" treatment response after two PicoWay treatments with the 785nm wavelength. Moreover, investigator assessments of tattoo clearance showed similar results to blinded evaluation findings.
The FDA also cleared Syneron non-invasive fat destruction device, UltraShape Power. for non-invasive reduction of abdominal circumference via fat cell destruction. UltraShape Power uses focused, pulsed mechanical ultrasound energy to target and destroy fat, offering measurable fat reduction to the abdominal area. UltraShape Power's USculpt transducer delivers 20 percent more energy than its predecessor. A recent clinical study with UltraShape Power's USculpt transducer documents a 32 percent reduction in subcutaneous fat thickness, positioning UltraShape Power as a powerful solution for non-invasive fat reduction.
UltraShape Power's ultrasound energy is applied to the skin in a proprietary pulse structure to ensure effective fat destruction with no damage to surrounding tissue including blood vessels, nerves and muscles, resulting in a safe and comfortable treatment experience. UltraShape Power's lighter transducer for high maneuverability enables the customized treatment of large and small fat pockets. The device also incorporates a sophisticated treatment and patient management software package combined with flexible communication options.
Allergan plc, received FDA approval to market Juvéderm Volbella XC for use in the lips for lip augmentation and for correction of perioral rhytids, commonly referred to as perioral lines, in adults over the age of 21. In clinical trials, Juvéderm Volbella XC was found to effectively increase lip fullness and soften the appearance of lines around the mouth in a majority of subjects through one year. Vycross blends different molecular weights of hyaluronic acid which contributes to the gel's duration. In addition, Juvéderm Volbella XC has been customized with a lower HA concentration (15 mg/mL), while still providing the long-lasting results healthcare providers expect from the Juvéderm collection of fillers. The safety and effectiveness of Juvéderm Volbella XC has been demonstrated in several clinical trials including the US pivotal study where 168 subjects were treated with Juvéderm Volbella XC.
The FDA granted clearance to Cynosure to market a new Laser Delivery System for PicoSure. Together with the FDA cleared 532nm and 755nm wavelengths, Cynosure's new 1064nm Laser Delivery System improves the multi-wavelength laser technology for removing the full color spectrum of tattoo inks in fewer treatments. The new 1064nm wavelength is designed for removal of black and other dark tattoo inks. Engineered to complement the highly versatile 755nm wavelength and the company's proprietary FOCUS Lens Array, the 1064nm and 532nm laser delivery systems enhance PicoSure's ability to remove tattoos and treat a range of dermatologic conditions including wrinkles, acne scars and pigmented lesions. The 1064nm wavelength will be offered as an upgrade to existing PicoSure customers.
The FDA approved the supplemental Biologics License Application (sBLA) for the expanded use of Amgen's Enbrel (etanercept), making it the first and only systemic therapy to treat pediatric patients (ages 4-17) with chronic moderate-to-severe plaque psoriasis.
The approval was based on results from a Phase 3 one-year study and its five-year open-label extension study to evaluate the safety and efficacy of Enbrel in pediatric patients, ages 4 to 17, with chronic moderate-to-severe plaque psoriasis. In addition to demonstrating significant efficacy, the adverse events were similar to those seen in previous studies in adults with moderate-to-severe plaque psoriasis.
Calling Sernivo (betamethasone dipropionate) Spray 0.05% a ‘trifecta’ for dermatologists who treat mild-to-moderate psoriasis, Josh Zeichner, MD says the product is “effective, safe and goes on easy even in hard-to-treat areas like the elbows.” Sernivo, an emulsion in a spray, is the first approved product from Dr. Reddy's, a US subsidiary Promius Pharma. It received the FDA’s nod in Feb 2016, and became available via prescription in June. Sernivo is indicated for the treatment of mild-to-moderate plaque psoriasis in patients 18 years of age or older.
An FDA advisory panel voted to greenlight Valeant’s IL-17 blocker brodalumab for the treatment of moderate-to-severe plaque psoriasis in adults. The committee voted 18 to 0 in favor of brodalumab injection, 210 mg, for adults with moderate-to-severe plaque psoriasis, along with conditions related to product labeling and post-marketing/risk management obligations.
The IL-17A blocker Taltz (ixekizumab) was FDA approved to treat adults with moderate-to-severe plaque psoriasis. Taltz is marketed by Indianapolis, Indiana-based Eli Lilly and Company. Given via 80 mg/mL injection, Taltz’s active ingredient is an antibody (ixekizumab) that binds to a protein (interleukin (IL)-17A) that causes inflammation. It is intended for patients who are candidates for systemic therapy, phototherapy or a combination of both.
Taltz’s safety and efficacy were established in three randomized, placebo-controlled clinical trials with a total of 3,866 participants with plaque psoriasis who were candidates for systemic or phototherapy therapy. The results showed that Taltz achieved greater clinical response than placebo, with skin that was clear or almost clear, as assessed by scoring of the extent, nature and severity of psoriatic changes of the skin.
Taltz is being approved with a Medication Guide to inform patients about risk of infection or allergic or autoimmune condition. Serious allergic reactions and development or worsening of inflammatory bowel disease have been reported with the use of Taltz. The most common side effects include upper respiratory infections, injection site reactions and fungal (tinea) infections.
Pfizer Inc. will begin shipment of Inflectra (infliximab-dyyb) for injection, a biosimilar of REMICADE1 (infliximab) to wholesalers in the United States in late November 2016. INFLECTRA is approved for the treatment of:
• adult patients and pediatric patients (ages six years and older) with moderate to severely active Crohn’s disease who have had an inadequate response to conventional therapy;
• adult patients with moderate to severely active ulcerative colitis who have had an inadequate response to conventional therapy; and
• moderate to severely active rheumatoid arthritis in combination with methotrexate; active ankylosing spondylitis; active psoriatic arthritis; and chronic severe plaque psoriasis.
Amjevita (adalimumab-atto) was FDA approved as a biosimilar to Humira (adalimumab) for multiple inflammatory diseases.
Amjevita is approved for the following indications in adult patients:
• moderate-to-severe plaque psoriasis;
• active psoriatic arthritis;
• moderate-to-severe rheumatoid arthritis;
• active ankylosing spondylitis (an arthritis that affects the spine);
• moderately to severely active Crohn’s disease;
• moderately to severely active ulcerative colitis.
Amjevita is also indicated for moderately to severely active polyarticular juvenile idiopathic arthritis in patients four years of age and older.
The FDA’s approval of Amjevita is based on review of evidence that included structural and functional characterization, animal study data, human pharmacokinetic and pharmacodynamics data, clinical immunogenicity data and other clinical safety and effectiveness data that demonstrates Amjevita is biosimilar to Humira. It has been approved as a biosimilar, not as an interchangeable product. Like Humira, the labeling for Amjevita contains a Boxed Warning to alert health care professionals and patients about an increased risk of serious infections leading to hospitalization or death. The Boxed Warning also notes that lymphoma and other malignancies, some fatal, have been reported in children and adolescent patients treated with tumor necrosis factor blockers, including adalimumab products. The drug must be dispensed with a patient Medication Guide that describes important information about its uses and risks.
The FDA approved Erelzi for multiple inflammatory diseases. Erelzi is a biosimilar to Enbrel (etanercept), which was originally licensed in 1998. The new approval is the largest marketed drug targeted to date by an FDA-approved biosimilar, FierceBiotech reports.
Erelzi is administered by injection for the treatment of active psoriatic arthritis, including use in combination with MTX in psoriatic arthritis patients who do not respond adequately to MTX alone; chronic moderate-to-severe plaque psoriasis in adult patients (18 years or older); moderate-to-severe rheumatoid arthritis, either as a standalone therapy or in combination with methotrexate (MTX); moderate-to-severe polyarticular juvenile idiopathic arthritis in patients ages two and older and active ankylosing spondylitis.
The FDA’s approval of Erelzi is based on review of evidence that included structural and functional characterization, animal study data, human pharmacokinetic and pharmacodynamics data, clinical immunogenicity data and other clinical safety and effectiveness data that demonstrates Erelzi is biosimilar to Enbrel.
Erelzi contains a Boxed Warning to alert health care professionals and patients about an increased risk of serious infections leading to hospitalization or death, including tuberculosis, invasive fungal infections (such as histoplasmosis) and others. The Boxed Warning also notes that lymphoma and other malignancies, some fatal, have been reported in children and adolescent patients treated with tumor necrosis factor blockers, including etanercept products. The drug must be dispensed with a patient Medication Guide that describes important information about its uses and risks.
The FDA approved Differin Gel 0.1% (adapalene), a once-daily topical gel for the over-the-counter (OTC) treatment of acne in people 12 years of age and older. Differin Gel 0.1% is the first retinoid to be made available OTC for the treatment of acne, and contains the first new active ingredient for acne treatment for OTC use since the 1980s.
Differin Gel 0.1% was originally approved in 1996 as a prescription product for the treatment of acne vulgaris in patients 12 years of age and older. Differin Gel’s safety and efficacy were initially established based on five clinical trials in people with mild-to-moderate acne. To support approval for OTC marketing, the data accrued from 1996-2016 on post-marketing safety, data from consumer studies and data from a maximal use trial were submitted.
Overall, results from the consumer studies showed that consumers can understand the information on the OTC label, appropriately select whether the product is right for them, and use the product appropriately. The maximal use trial, a study of absorption of the drug through acne-affected skin when applied daily over a large surface area, demonstrated that absorption is limited, thus supporting safe use of Differin Gel 0.1% by people using it OTC.
Differin Gel 0.1% is distributed by Galderma Laboratories, L.P.
Biofrontera AG initiated the US commercial launch of its combination topical prescription drug Ameluz and medical device BF-RhodoLED, which has been FDA approved to treat mild to moderate actinic keratosis (AK) on the face and scalp. Ameluz is used in combination with the medical device BF-RhodoLED for photodynamic therapy treatment (PDT). FDA approval of the combination treatment covers lesion-directed and field-directed treatment of AK. Field-directed treatment is recommended by dermatological guidelines due to the observation that early AKs are particularly prone to progression to squamous cell carcinoma. In addition, after field-directed treatment with Ameluz, patients benefit from the long-lasting skin rejuvenation effect demonstrated in Biofrontera's Phase 3 trials.
The FDA approved Eucrisa (crisaborole) ointment to treat mild-to-moderate eczema in patients two years of age and older. Eucrisa, applied topically twice daily, is a phosphodiesterase 4 (PDE-4) inhibitor, although its specific mechanism of action in atopic dermatitis is not known.
The safety and efficacy of Eucrisa were established in two placebo-controlled trials with a total of 1,522 participants ranging in age from two years of age to 79 years of age, with mild to moderate atopic dermatitis. Overall, participants receiving Eucrisa achieved greater response with clear or almost clear skin after 28 days of treatment.
The FDA has accepted for priority review the Biologics License Application (BLA) for dupilumab from Regeneron Pharmaceuticals, Inc. and Sanofi for the treatment of adult patients with inadequately controlled moderate-to-severe atopic dermatitis (AD). The application has been given a Prescription Drug User Fee Act (PDUFA) target action date ofMarch 29, 2017. The investigational antibody therapy dupilumab inhibits signaling of IL-4 and IL-13, two key cytokines required for the type 2 (including Th2) immune response, which is believed to be a major driver in the pathogenesis of the disease.
The BLA for dupilumab contains data from three Phase 3 pivotal studies in the global LIBERTY AD program that included more than 2,500 patients. The goal of the studies was to evaluate dupilumab as monotherapy (SOLO 1 and SOLO 2) and in concomitant administration with topical corticosteroids (CHRONOS), in adult patients with moderate-to-severe AD whose disease is not adequately controlled with topical prescription therapies. In 2014, the FDA granted Breakthrough Therapy designation to dupilumab for the treatment of adults with moderate-to-severe AD who are not adequately controlled with topical prescription therapies or for whom these treatments are not appropriate.
Dupilumab is currently under clinical development and its safety and efficacy have not been fully evaluated by any regulatory authority. If approved, dupilumab would be commercialized by Regeneron and Sanofi Genzyme, the specialty care global business of Sanofi.
The European Commission (EC) and the FDA have granted Orphan Drug Designation to Boehringer Ingelheim's nintedanib for the treatment of systemic sclerosis (SSc, also known as scleroderma), including the associated interstitial lung disease (SSc-ILD).
SENSCIS™, the largest trial to date in this disease area, is evaluating nintedanib to understand the disease process and potential benefit of the compound to treat SSc-ILD. Systemic sclerosis, commonly referred to as "scleroderma," is a disfiguring, disabling and potentially fatal rare disease that can cause scarring of the skin, lungs (SSc-ILD) and other organs. Worldwide, an estimated two million people have systemic sclerosis (also known as scleroderma) and up to 90% may develop some degree of lung scarring. In the U.S., it is estimated that SSc-ILD affects up to 86,000 people. SSc-ILD indicates a poor prognosis and accounts for 35 percent of all disease-related deaths.
Orphan Drug Designation is generally granted by the EC for a therapeutic agent intended to treat a life-threatening or chronically debilitating disease that affects no more than five people in 10,000, and for which there is no or only unsatisfactory treatment options or the medicine will be of significant benefit to those affected by that condition. In the US, the FDA grants the status to investigational compounds intended for the safe and effective treatment, diagnosis or prevention of rare diseases or disorders that affect fewer than 200,000 people.
The FDA also granted Orphan Drug Status to TXA127 as a potential treatment for the rare genetic skin disorder Recessive Dystrophic Epidermolysis Bullosa (RDEB).
TXA127 developer, Tarix Orphan LLC, is also partnering with DEBRA Austria, a research collaboration aimed at furthering the development of TXA127 as a potential treatment for RDEB. Under the agreement, DEBRA will fund a preclinical study of TXA127 that is designed to definitively show the efficacy of TXA127 in a mouse model of RDEB.
TXA127, a pharmaceutical formulation of the natural Angiotensin (1-7) peptide, interferes with the TGF beta pathway, which is involved in the pathophysiology of DEB as well as several other serious orphan diseases. Previous preclinical studies with TXA127 have shown its ability to reduce the fusion of digits, a symptom in RDEB mice that is analogous to mitten deformity common in patients with severe RDEB.
Also this year, the FDA issued a new rule that means antibacterial soaps will soon be gone from store shelves. This final rule applies to consumer antiseptic wash products containing one or more of 19 specific active ingredients, including triclosan and triclocarban. Triclosan used in 93 percent of liquid products labeled "antibacterial" or "antimicrobial" - at least 2,000 different products, according to the FDA.
Companies will no longer be able to market antibacterial washes with these ingredients because manufacturers did not demonstrate that they are safe for long-term daily use and more effective than plain soap and water in preventing illness and the spread of certain infections.
Some manufacturers have already started removing these ingredients from their products. They will have one year to comply with the rulemaking by removing products from the market or reformulating (removing antibacterial active ingredients) these products. This rule does not affect consumer hand “sanitizers” or wipes, or antibacterial products used in health care settings.
The FDA accepted Medimetriks Pharmaceuticals, Inc.'s New Drug Application (NDA) for their novel impetigo treatment, ozenoxacin cream, 1%. Ozenoxacin cream is a non-fluorinated quinolone. The Prescription Drug User Fee Act (PDUFA) date for the completion of FDA's review is June 22, 2017. Medimetriks licensed exclusive US commercialization rights to ozenoxacin from Ferrer, a Spanish pharmaceutical company, in March 2014 and announced the completion of the second successful Phase 3 pivotal trial in July 2015. Both Phase 3 pivotal studies demonstrated the superiority of ozenoxacin cream, 1%, applied topically twice daily for 5 days versus placebo on both the clinical and bacteriological endpoints. In the studies, ozenoxacin demonstrated superior bacteriological cure compared to placebo as early as visit 2 (day 3-4), and showed excellent antibacterial activity against a broad range of bacteria. The studies demonstrated that ozenoxacin was safe and well tolerated in both the adult and pediatric populations aged 2 months and older. Medimetriks submitted the ozenoxacin NDA to FDA in June 2016.
The FDA awarded Oculus Innovative Sciences, Inc. 510(k) clearance for its new post-dermal-procedures product. Under the supervision of a healthcare professional, the product is intended for the removal of foreign material including microogranisms and debris from post¬dermal procedures. Oculus’ dermatology division, IntraDerm, will begin marketing the post¬dermal-procedures product in the United States beginning in March 2017.
Allergan’s TEFLARO (ceftaroline fosamil) is now indicated for pediatric patients, making it the first branded IV antibiotic approved for this population in more than a decade.
The FDA approved the company's supplemental sNDA allowing the antibiotic to be used in pediatric patients two months of age to less than 18 years of age with acute bacterial skin and skin structure infections (ABSSSI), including infections caused by methicillin-resistant Staphylococcus aureus (MRSA), and community-acquired bacterial pneumonia (CABP) caused by Streptococcus pneumoniae and other designated susceptible bacteria. It is administered by intravenous (IV) infusion in five minutes to one hour.
Results from the clinical studies in pediatric patients showed that TEFLARO demonstrated a safety profile that was compatible with treatment of ABSSSI and CABP at the clinical dosages studied. The safety findings were similar to those seen in the adult studies, and no safety concerns were identified beyond those already known to be cephalosporin class effects.
The FDA issued draft updated recommendations to help manufacturers determine when they are required to notify the FDA about modifications made to certain medical devices already on the market, including a separate guidance applicable to software devices.
When finalized, the two guidances will provide improved clarity, regarding minor changes that do not require FDA review, and help ensure that the FDA receives appropriate submissions for modifications that do require premarket review by the agency.
The draft guidance documents apply to medical devices the FDA clears through premarket notification; manufacturers submit a “510(k)” document that demonstrates the device is substantially equivalent to another marketed device not subject to premarket approval (PMA). Federal law requires manufacturers to submit a new 510(k) when changes or modifications made to an existing device could significantly affect its safety or effectiveness or the manufacturer makes a major change or modification in the intended use of the device.
The draft recommendations describe how manufacturers should consider the risk presented by the device modifications when determining if they should submit a new 510(k). When finalized, they will replace an earlier guidance issued in 1997.
The FDA first drafted an update to the 1997 guidance five years ago, but the agency withdrew that draft guidance after passage of a 2012 federal law, which required the agency to revisit its policy on 510(k) device modifications. The FDA complied with these requirements, in part by holding a full-day public meeting on this topic in 2013 and publishing a Report to Congress on 510(k) device modifications in 2014.
The draft guidances maintain the structure outlined in the 1997 guidance, but with specific revisions to address key issues raised during interactions with and submissions to the FDA following the release of the 2011 draft. These discussions highlighted that certain vague terms in the 1997 guidance should be clarified, as some decision-making points have raised questions among manufacturers about whether or not they are required to submit a new 510(k). This clarification is intended to help ensure that devices with significant modifications are not being sold or distributed without FDA review.