By ANETTE BREINDL
BB&T
And JEFFREY BERG, PhD,
BB&T Contributing Writer

WASHINGTON — For attendees flying into the nation’s capitol for the 65th annual meeting of the American Academy of Dermatology (AAD; Schaumburg, Illinois) in early February, the Skymall catalog made bringing a dermatology product to market look easy: a company called Hollywood Gadgets promised wrinkle-free skin with the help of a gene therapy machine — costing all of $59.95 — and claiming it could electronically restore “what dermatologists call the ‘S Complex Gene’ . . . via a ‘copy sound wave.’”

But at an AAD session on “Translational Research in Dermatology,” the speakers shared tales of their experiences mostly with the opposite problem: getting dermatologic treatments to market when you have sound science but not a whole lot to show on the product side.

Barbara Gilchrest, professor and chair of dermatology at Boston University, suggested that one way to bring a dermatology drug to market is to pretend it’s something else. In particular, she suggested “piggybacking” dermatology drugs onto other indications. The rationale behind this approach, she explained, is that several factors make drug developers more likely to spend their money elsewhere, rather than on dermatology products.

For one thing, though cosmetics are obviously a huge business, the medical dermatology market for most diseases is comparatively small. And most skin diseases are chronic but not life threatening.

Lots of data for small market

In terms of regulatory scrutiny, this means “the FDA is going to insist on a huge amount of safety data,” Gilchrest said. “And the fact that there is a small market on the other end is not their problem. It is yours.”

Gilchrest’s academic research is on t-oligos, which are short artificial analogues of telomeres. Originally, Gilchrest’s plan was to develop t-oligos as skin protection; when she published data showing a specific t-oligo can protect skin from ultraviolet light damage in 1994, “we thought that we would have a protective agent for human skin within 12 months,” she told the audience.

These days, her outlook is more sober, thanks to her experiences with a technology transfer office that was “overwhelmed and under-funded,” a pharma company that changed its focus, and a biotech that went belly-up after a late-stage clinical failure. She is now the co-founder of Boston University spin-out SemaCo (Salzburg), and hopes that t-oligos can be developed as cancer therapeutics. SemaCo is pursuing the development of t-oligos, which interact with telomeres to selectively kill cancer cells, as an oncology product.

Cash flow and accumulated safety data from product approval in the oncology arena could be used in furthering their approval as protective dermatology agents. Gilchrest noted, though, that the newest try may not pan out any more than earlier ones did: developing t-oligos as cancer therapeutics “is just the next in a long line of pathways that we are exploring,” she told her audience. “But it is the hoped-for path now.”

Avoiding ‘founderitis,’ ‘close watching’

While there is a perception in the business community that academics suffer from founderitis — a belief by scientists that they are qualified to run a business based on their discoveries — all three speakers founded their companies only after out-licensing efforts had failed.

All three noted that finding a high-caliber business executive had been both one of their primary goals and one of their greatest challenges. Kenneth Cooper, professor of dermatology at Case Western University (Cleveland, Ohio), said that co-founding is “effective, if you have the time,” but noted that in his experience, “executives need close watching.”

Despite their tales of woe — one scientific co-founder who spoke at the panel was fired from the company by his CEO — each of the researchers noted that trying to bring a product to market is rewarding, and can prevent a laboratory from getting bogged down in what one panelist termed “mechanstic questions with no relevance to therapeutic success.”All speakers at the panel could back up their science with sound experiments published in top-flight journals.

And while pharma or pharma-like products are everywhere in this conference, it also features an expanding list of device and device-like therapies.

Dermal filler developments

The role of dermal fillers in non-surgical facial rejuvenation continues to grow dramatically. In addition to their use in the treatment of wrinkles, folds and scars, there is an increased use of these materials for facial contouring.

This has been made possible due to advances in dermal fillers which allow more volume, better moldability and longing lasting products. Looking beyond the much publicized marketing tactics in the head-to head competition of the cross-linked hyaluronic acid dermal fillers, Juv derm (and its next generation Juv derm Ultra) from Allergan (Irvine, California) and Restylane from Medicis Pharmaceutical (Scottsdale, Arizona), are several newly approved and noteworthy alternatives.

BioForm Medical (San Mateo, California), just days before the convention, received FDA clearance for Radiesse, a biocompatible, non-allergenic filler for soft tissue augmentation to reduce the appearance of wrinkles and skin folds around the mouth and nose, and for facial fat loss (lipoatrophy) which occurs in HIV patients which can result in sunken cheeks and hollow eyes. It is comprised of hydroxyapatite in a carrier of carboxymethyl cellulose. Its previous use in the U.S. was restricted to the bulking of vocal folds. The company has a partnership with Boston Scientific (Natick, Massachusetts) for marketing Coaptite, a gel that is injected into the wall of the urethra, for treating stress urinary incontinence in women.

Dermik Laboratories (Bridgewater, New Jersey), a subsidiary of Sanofi-Aventis (Paris), markets Sculptra, injectable polylactic acid for the restoration and/or correction of facial fat loss in HIV patients. It is sold in Europe under the New-Fill name for use in a variety of facial volume and contour deficiencies, such as skin creases, wrinkles, folds and scars.

Anika Therapeutics (Woburn Massachusetts) has a worldwide development and commercialization agreement with Galderma Pharma (Lausanne, Switzerland), a joint venture between Nestle (Vevey, Switzerland) and L’Oreal (Paris), for cosmetic tissue augmentation. The cross-linked hyaluronic-acid-based injectable soft tissue filler contains lidocaine and was FDA-approved at the end of 2006 for use in the correction of facial wrinkles, scar remediation and lip augmentation. Anika said it anticipates filing amendments with FDA and European Union regulators to enhance product features prior to its market launch, estimated for the second half of 2007.

Artes Medical (San Diego) last month reported its initial shipments of ArteFill, an injectable, non-resorbable dermal filler that received FDA clearance in October 2006. It consists of 80% purified bovine collagen and 20% polymethylmethacrylate microspheres suspended within the collagen carrier. It requires a skin pretest prior to use. ArteFill is not being sold outside the U.S.

Dr. Mark Rubin, a professor of dermatology at the University of California, San Diego, presented five-year safety and efficacy data for ArteFill. The most common adverse events observed during the study were lumpiness, persistent swelling or redness at the injection site, which are similar to those seen with other dermal fillers.

More minimally invasive

Paralleling many areas of traditional medicine that are seeking less invasive treatments, dermatology is clearly in the forefront of attempting to do the same both as a marketing tool and in response to clear patient preference.

Dr. Michael Kaminer, assistant professor of dermatology at Yale University (New Haven, Connecticut) and Dartmouth University (Hanover, New Hampshire), discussed the benefits of the latest minimally invasive cosmetic procedures that yield improved outcomes compared to traditional facelift surgery. These include monopolar radio frequency (RF) skin tightening and thread lifts that can tighten the face without surgery and can create a more natural appearance.

RF technologies use intense heat delivered deep into the dermis layer. It is accompanied by protective skin cooling to produce collagen remodeling and tightening. The effect is gradual, with optimal results occurring in four to six months. Unlike invasive counterparts, monopolar RF skin tightening can be performed without injuring the epidermis, resulting in virtually no downtime for the patient.

The thread lift is an in-office procedure for improving sagging skin. Tiny suture-like hooks are implanted underneath the hairline to pull the skin upward. The procedure requires only a local anesthetic and takes one or hours to perform. The results are expected to last from seven to 10 years. The thread lift procedure can be enhanced when paired with skin resurfacing or filler.

Thermage (Hayward, California) markets the ThermaCool monopolar, capacitively coupled RF device which delivers, via its single-use ThermaTip attachment, RF energy into the outer layers of the skin. The noninvasive treatment provides tissue contouring and tightening by reducing the sagging that occurs as part of the aging process. The product can be used from head to toe and the company says results last two to three years.

The company completed its IPO offering late last year, offering 6 million shares of commons tock at $7 a share, adding to it the sale of over-allotments to underwriters. It reports placing 2,000 units worldwide, with about half of its sales in international markets and 70% of its revenues from its disposable tips.

Surgical Specialties (Reading, Pennsylvania), a subsidiary of Angiotech Pharmaceuticals (Vancouver) and marketer of sutures, featured its Contour Threads, self-anchoring and knot-less polypropylene threads with barbs that are used in a minimally invasive surgical approach for elevation and fixation of skin. They are the only products with FDA clearance for elevation and fixation of the brow, mid-face and neck.

Diverse offerings via photodermatology

Dr. Amy Taub, a dermatologist on staff at Northwestern University Medical School (Chicago) made a presentation on light sources and heat-based technologies that she said mark the first new therapies to treat acne in more than 20 years. They work by altering the structure of the oil glands.

DUSA Pharmaceuticals (Wilmington, Massachusetts) broadened the base of its business from its initial photodynamic therapy (PDT) system using Levulan (amino levulinic acid) as a first-line therapy for treating pre-cancerous actinic keratoses, with the acquisition of Sirius Laboratories (Vernon Hills, Illinois), which markets drugs for acne (topical and oral) and rosacea (topical). The company is in clinical development of Levulan combined with its BLU-U Blue light for PDT treatment of moderate to severe inflammatory acne. The illuminator alone has FDA clearance for treatment of moderate inflammatory acne.

PDT using red LED light is indicated for the treatment of superficial basal cell carcinoma and Bowen’s disease. A course on the Global Outlook of PDT, led by Dr. Michael Gold, from Vanderbilt University (Nashville, Tennessee), with the participation of 15 other dermatologists from around the world, affirmed that PDT is an effective treatment of acne, photo-damaged skin and for chemoprevention.

Radiancy (Orangeburg, New York/Yavne, Israel) launched two home-use aesthetic devices at the AAD meeting. The ClearTouch Lite is a prescription device used with Levulan in the home for acne phototherapy. It is a scaled-down version of its more powerful SkinStation light and heat energy (LHE) device for professional use. The handpiece is pressed against the skin, and the light trigger is then pushed and held until it stops flashing. Radiancy’s Facial SkinCare device is portable and uses LHE technology to lighten benign pigmented lesions and for skin rejuvenation. It is intended for use at home between photorejuvenation sessions.

CureLight (Gladstone, New Jersey/Or Akiva, Israel) markets Clear 100XL in a UV mode (405-420 nm wavelengths) for treating acne and in the near infrared mode (850-900nm) for the photorejuvenation of aging skin. Nitric oxide is released into vascular muscles to enhance vessels dilatation and increase blood circulation which leads to better cellular oxygenation. Its newest product launched at the meeting is XLulight for treating cellulite and reducing its circumference.

Photo Therapeutics (Lake Forest, Californ-ia/Cheshire, UK) featured its Omnilux phototherapy product line which employ narrowband LEDs. Depending on the emitted wavelength, these devices can be use to treat acne (415 nm), psoriasis and reduction of periorbital wrinkles (633 nm) and muscular pain (830 nm). When used in conjunction with Levulan, the products can be utilized to treat non-melanoma skin cancers, severe acne and actinic keratoses.

Daavlin (Bryan, Ohio) markets a line of full-body UVA and UVB phototherapy cabinets used for treating skin disorders such as psoriasis, vitiglio, eczema and scleroderma.

Rhytec (Waltham, Massachusetts) displayed its Portrait PSR3 equipment that creates a plasma from nitrogen gas that penetrates deep into the dermis for skin regeneration and reduction of fine, moderate and deep wrinkles. Several days following the treatment a new epidermis emerges as the old skin starts to shed. It causes less trauma than ablative procedures and healing is rapid. There are no comparable plasma-generating products on the market for aesthetic procedures.

Skin resurfacing with lasers

The exhibition was a showcase of more than 25 laser companies touting new features of their products for aesthetic procedures and riding a continuing wave of interest from consumers and investors in the use of lasers in this sector. These devices were being promoted for a broad range of applications: removal of unwanted hair, smoothing of wrinkles and melting body fat — plus the latest rage, tightening skin.

Two of the skin resurfacing procedures using the minimally invasive approach are fractional resurfacing and superficial ablative resurfacing. These technologies use laser and are proving successful in gently smoothing out uneven pigmentation, wrinkles and irregular texture. Fractional resurfacing is performed in three to five treatments for most patients. This method reaches deep into the dermis to promote new collagen formation. The untreated healthy skin remains intact and actually aids in the repair process by promoting rapid healing with only a day or two of downtime.

Superficial ablative resurfacing treats fine lines and wrinkles, as well as uneven pigmentation, with an erbium laser that removes skin as thin as a few microns at a time. This technique significantly improves the efficacy of skin resurfacing, while eliminating many of risks inherent with older devices. There are only a few days of downtime following the procedure.

Biocellulase (Merrimack, New Hampshire), a new entrant in this market was featuring its laser-assisted device to improve the appearance of cellulite. The company filed for FDA approval for the device in June 2006.

Lasers for removing skin ‘art’

One of the expanding areas for laser use is the increasing popularity of tattoos. With the increased popularity of tatooing over the past 10 years, it also means more people not so happy with their skin art. A 2004 survey of people between the ages of 18 and 50 years has indicated that 24% of the 500 respondents had a tattoo, but that 17% of these had considered having them removed and 5% had the tattoo covered.

A variety of tattoo removal methods are being used, such as chemical, mechanical surgical and thermal, prior to the advent of laser removal. These earlier methods left hypo- or hyper-pigmentation as well as scarring. Due to its specific absorption by the pigment, the gold standard for tattoo removal is giant pulsed lasers. Dark blue, red, some lighter blues and green inks respond well to tattoo treatment via laser.

The best candidates for tattoo removal are people with light skin who have a black ink tattoo. Tattoo inks are the least regulated of substances that are allowed to be injected into the human body, though this may change. In January of last year Switzerland passed a federal law regulating the use of tattoo inks as well as the action of tattooing itself.

Diagnosing/treating skin

3Gen (San Juan Capistrano, California) displayed DermLite dermoscopes for lesion visualization and the early detection of skin cancer. These devices employ LED technology and a patented polarization system in a handheld device. Dermilite FOTO can be attached to a camera for photographing skin lesions.

Cortex Technology (Hadsund, Denmark) markets DermaScan C high-resolution ultrasound units that use image analysis software and scan at frequencies of 50MHz to provide high definition skin imaging in real time. The company also sells the CryPro liquid nitrogen cryosurgical equipment in Mini (350 ml) and Maxi (500 ml) capacities that is used for the removal of many types of skin lesions.

Clarisonic (Bellevue, Washington) featured its skin care brush for deep skin cleansing that is marketed primarily to dermatologists and high-end spas. It employs sonic oscillations (300 movements/second) to deeply cleanse, stimulate and clarify the skin by unclogging pores without stripping the skin. Dermatologists and aestheticians reported improved absorption of serums and moisturizers following cleansing with the Clarisonic device. Several posters were presented at the conference on this method, including a safety and efficacy study which disclosed its use for treating seborrheic dermatitis.

Mattioli Engineering (McLean, Virginia) featured its Ultrapeel Transderm Ionto system, an alternative to injections that can deliver micro and macro molecules after treatment with its Ultrapeel II microdermabrasion unit. It has FDA approval for the local delivery of ionic drug solutions and can be used for skin resurfacing and revitalization, cellulite treatment, pre-laser treatment and for mesotherapy applications.

The Transderm Ionto system is being used for transdermal delivery of hyaluronic acid, carnitine, aminophilline, vitamins and steroids. A poster presentation was made which showed that pulsed current iontophoresis was effective in the transdermal delivery of botulinum toxin type A, commonly known as Botox.