By  on February 8, 2008

It was standing room only last October as the plush chairs in the Soho House screening room quickly filled up. The crowd wasn’t there for an advance look of the latest Hollywood blockbuster, though.

The topic on this day was adult stem cells. More specifically, how a new antiaging cream from Christian Dior, called Capture R60/80 XP, can purportedly help preserve and maximize the life of adult stem cells present in the basal layer of the skin, and thus help prevent the formation of wrinkles.

There to present the case was Carlo Pincelli, professor of dermatology and director of research in the laboratory of cutaneous biology, University of Modena and Reggio Emilia, Italy, whose work in adult stem cells informed the creation of the cream, as well as Eric Perrier, director of research and development for LVMH Parfums et Cosmetiques.

Those in attendance were beauty editors, but the session was more advanced biology than typical beauty launch event—and it wasn’t an anomaly. The gulf between cosmetics and pharmaceuticals is getting ever narrower as the language of skin care marketing—with its catchphrases about cellular health, Botox-like effects and collagen stimulation—seems to teeter on the drug precipice. Meanwhile, biotechnology and pharmaceutical companies, once isolated in their research towers, are bulldozing into beauty territory armed with scientific backgrounds to woo a demanding public.

“Cosmeceuticals today work better in antiaging skin care than many drugs did 15 years ago,” says Rex Bright, chief executive officer of Skin Medica. “The technology has gotten very sophisticated.”
“Twenty years ago when we first started making products, very often we would do 12-week clinicals, and we would see 30 to 40 percent reduction in wrinkles,” says Tom Mammone, Clinique’s executive director of biological research and development. “Now, we are doing four-week clinicals and [seeing] 60 percent reduction in wrinkles.

“You used to buy an antioxidant for a few dollars a kilo,” he continues. “We have materials that are $20,000 to $40,000 a kilo. They are expensive materials, and they’re worth it because they are effective.”

The market for such products is larger than ever before, fueled by the Baby Boom generation whose quest for eternal youth has led beauty companies to scour the earth for ever more potent ingredients, expand their research budgets exponentially and partner with pharmaceutical and biotech firms and universities to stay on the cutting edge of antiaging research and medicine. While cosmetics companies are not publicly searching for a cure to wrinkles—only a drug could do that—they wouldn’t mind getting pretty damn close to at least a temporary fix.

To find that fix, temporary or otherwise, they’ve increased the breadth of their research. In addition to investing in their own labs, companies are betting that ever more efficacious (and lucrative) discoveries will be netted from partnerships with university research departments and pharmaceutical and biotech companies. Clinique, for example, teamed up with Cornell University’s department of dermatology last year to open the Clinique Skin Wellness Center at Weill Cornell. Dior helps support the exploration of stem cells at the Stanford Institute for Stem Cell Biology and Regenerative Medicine and Estée Lauder is among several that have turned to studies on aging and cellular metabolism conducted at Harvard University and the Massachusetts Institute of Technology when formulating its products.

Such affiliations can backfire, though, as happened when Cosmedicine teamed up with Johns Hopkins University. The brand recruited Johns Hopkins Medicine to consult on clinical trials and quantitatively measure product benefits; the university felt that some media stories overstated the relationship between the two, though, and publicly rebuked the brand. 

The ranks of biotechnology companies stepping up to the cosmeceutical plate are swelling as well. The Canadian company VitalScience Corp. has struck a deal with Genesis Genomics, which studies mitochondria, to develop DermaDNA, a line that customizes formulas to consumers’ DNA and is scheduled for a spring launch. GeneLink teamed up with Arch Chemicals to produce Dermagenetics, its line of DNA-customized skin care. DermaPlus, whose founder Burt Ensley spent 10 years at drug giant Amgen, is marketing DermaLastyl, while Helix BioMedix, which produces bioactive peptides, joined with DermaVentures to create P.A.C. Perfect (Peptide-powered Acne Control) late last year. Applied DNA Sciences, which specializes in DNA-based technologies, has begun providing cosmetics firms with an ingredient called DermalRX for products slated to hit shelves later this year.

Pharmaceutical companies, too, are jumping on the bandwagon—just not in the prescription market. Stiefel Laboratories, which markets prescription products for eczema, psoriasis and other skin conditions, launched Revaléskin last year; Valeant Pharmaceuticals markets Kinerase, and Allergan, the producer of Botox, partnered with Elizabeth Arden on Prevage and in January revealed a partnership with Clinique for a new line of physician-dispensed products. AGI Dermatics, Thiax Pharmaceuticals and Skin Medica all peddle beauty products, too.

And why not? Drug companies have quickly discovered that retail skin care is very profitable indeed. “The production of a drug can cost $10 million to $50 million or more,” says Christopher Zachary, chair of dermatology at the University of California, Irvine, “whereas the investment in the development of a cosmeceutical is likely to start in the tens of thousands [of dollars].”

At Skin Medica, the opening price for a drug is $15 million versus less than half a million dollars for a cosmeceutical; a drug takes three to five years to produce versus six to nine months for a cosmeceutical, according to ceo Rex Bright. Matthew Swanson, Stiefel’s executive director of aesthetic marketing, says it might take the company a decade to develop a drug. Revaléskin’s time in the pipeline was under a year.

The payoff is immediate. Consumers are shelling out an average of $53 per cosmeceutical product, according to The NPD Group. NPD projects that sales of prestige cosmeceutical products grew from $235 million in 2006 to $250 million in 2007, accounting for 11 percent of the total prestige skin care segment. The medical channel is also growing at a rate faster than the overall market, posting a 16 percent jump in 2007, according to Kline & Company.

Explosive growth is also coming from luxury-priced skin care, a category into which many of these products fit. In 2002, the ceiling price for a skin care product sold in department stores was $300. By 2005, it had reached $570 and by 2007, items priced at $1,200 were being sold on department store shelves.

The price of skin care may have no limits, but the level of efficacy does. The 1938 Food, Drug and Cosmetic Act instructs the U.S. Food and Drug Administration that a cosmetic is a substance people apply to make themselves pretty or clean. A drug has disease-related purposes and affects “the structure or any function of the body of man.”

As the science has become more advanced, however, the distinction between the two today is often not so tidy. “People sometimes look for bright lines that separate one category from another. Those bright lines don’t really exist,” says John Bailey, executive vice president for science at the Personal Care Products Council. “Science does march on. There may be a better understanding of ingredient activity. At the end of the day, the FDA bases [judgments] on the intended uses based on the claims associated with a product.”

The relative lack of FDA scrutiny has stoked a Wild West atmosphere in the cosmeceutical market. Companies are angling for payouts even if they may have fool’s gold in their pockets.

Amid marketing distortions, it is difficult to pin down exactly how powerful skin care products are becoming and their proximity to drug performance remains an open debate. The gold standard in antiaging pharmaceutical skin care remains retinoids. Physician Albert Kligman invented Retin-A, the first retinoid, in 1967 to treat acne.

In the Eighties and Nineties, OTC retinol products and exfoliating alpha hydroxy acids inundated the market, undeniably more efficacious than the comparatively inert moisturizers that came before. Progress would dictate that the current antiaging skin care crop pushes ahead.

“AHAs and retinols really started the skin care revolution,” says Daniel Yarosh, president and chairman of AGI Dermatics, which markets the skin care line Remergent. “They provided immediate benefits and set the bar. What you’re starting to see now are products that are reprogramming the skin and having a longer-term effect.”

Newer, Faster, Better

As the skin care wars have escalated, so has the race to identify and market the latest wonder molecule or ingredient. Antioxidants, combatants of skin-damaging free radicals, have some of beauty’s brainiest scientists working overtime.

One chief antioxidant warrior is Joseph A. Lewis 2nd. A pioneer of glycolic acid and co-founder of skin care brand Priori, Lewis’ most recent feat is idebenone, a bioengineered form of the naturally occurring coenzyme Q10 that’s meant to target mitochondria. Originally introduced in 2005, it’s the lead ingredient in the Allergan-Elizabeth Arden line Prevage. Priori products with idebenone showed a 44 percent decrease in fine lines and wrinkles in a double-blind, three-week study with 21 subjects.

Ergothioneine is another highly touted antioxidant, patented by AGI Dermatics. Typically harvested from mushrooms, it’s a key ingredient in Remergent products and is contained in select Kinerase and Cellex-C items, too.

Resveratrol, a polyphenol with antioxidant properties, continues to make headlines. Found in the skin of grapes, resveratrol is said to trigger enzymes called sirtuins by replicating calorie restriction to prolong cell life span and accelerate cellular repair. Most companies draw upon studies conducted at Harvard and MIT on sirtuin enzymes’ influence on cell longevity. “The benefits now that we are discovering is that it will slow the aging process by optimizing metabolizing in the skin,” says Clinique’s Mammone. Caudalie, Davi and Dior also market products with resveratrol. 

This spring, Estée Lauder is launching Re-Nutriv Ultimate Youth Cream with resveratrate, described as a stronger and more stable take on resveratrol. “It is a very serious advance for us because for the first time we are entering in the area of genetic aging,” says Daniel Maes, vice president of global research and development at Lauder. “What we have is a molecule that activates longevity genes and makes the genes more sturdy and resistant to UV damage.”

Rounding out the headline-grabbing antioxidants is coffeeberry, the star of Stiefel Pharmaceutical’s Revaléskin. Stiefel touts coffeeberry’s antioxidant strength by citing its ORAX score, or Oxygen Radical Absorbance Capacity, a standard used by the U.S. Department of Agriculture to evaluate the levels of oxygen radical absorbance in food. Coffeeberry’s score is 15,000 compared with green tea’s 10,000 to 11,000. In addition, Stiefel commissioned two studies, including one by Dermatology Consulting Services that demonstrated statistically significant improved skin tone and brightness after six weeks in 50 females from 30 to 50 years old.

Peptides and human growth factors share billing with antioxidants in the latest wave of cosmeceuticals. The two come from the biotech and medical fields, where their function is to heal wounds. Growth factors are proteins that play a role in cell proliferation. Still in their scientific infancy, no one has conclusively put a finger on exactly how they work.

Plastic surgeon Gregory Bays Brown introduced a bioengineered version of epidermal growth factor to skin care when he launched RéVive in 1997. Since then, their numbers have risen steadily.

“As you age, think of the new cells as a Xerox copy,” explains Bryan Johns, ceo of Innovative Skincare, which launched a line called Youth Complex last year. “The stem cells are the original cell. Then, they copy and copy. By the time you get to thousands of them, it is not nearly as clear or efficient as the original,” he continues. “A growth factor brings back to the copy the formula that makes it behave in the optimum state.”

A number of different growth factors are now used in skin care: RéVive has added insulin-like growth factor and keratinocyte growth factor. There’s also vascular endothelial growth factor and TGF-beta, which Richard Fitzpatrick, a San Diego-based dermatologist, calls the “most powerful growth factor to stimulate collagen” currently known. One or the other is found in TNS, Azure Cosmeceuticals, DDF and NeoCutis products.

Peptides are akin to mini growth factors, according to Fitzpatrick. They are chains of amino acids intended to enhance skin thickness. Peptides made a splash with pal-KTTS, also known as palmitoyl pentapeptide-3 or matrixyl, the backbone of StriVectin and Olay’s Regenerist line. Pal-KTTS has been vetted with several double-blind studies providing evidence that it decreases wrinkles and roughness at certain concentrations.

The next generation of peptides has not withstood the same level of review yet. One called argirilene, otherwise known as acetyl hexapeptide-3, has been compared to injectables because it can reportedly relax muscles and plump the face. “There are nerve signals in the skin, and they send messages from one synapse to another synapse. These peptides block certain receptor sites from getting to their destination, which relaxes muscle,” says April Zangl, ceo of Azure Cosmeceuticals, which uses argirilene.

Cytokinins, a class of plant-derived hormones that promote cell division and were first identified in the Fifties at the University of Wisconsin, have had staying power in the cosmeceutical field. Valeant Pharmaceuticals’ Kinerase products are driven by kinetin and zeatin, both in the cytokinin family. This month, pharmaceutical company Triax is launching Lumeris, a brand with pyratine-6, a second-generation cytokinin.

Enzymes, too, are increasingly popular, and are drawn from a variety of sources, including plant, animal or synthetic. Telomerase enzymes that protect telomeres—stretches of DNA at the end of chromosomes that safeguard genetic information and are thought to be a factor in aging—have sparked recent interest. Jan Marini Skin Research’s Age Intervention Regeneration Booster incorporates a telomerase enzyme, and Canadian skin care brand Isomers’ Renovage products feature teprenone, an enzyme from yeast thought to act on telomeres. “It helps to reset the cells’ aging clock,” says Manuela Marcheggiani, co-founder of Isomers. “That’s an area that is emerging because they’re doing an intense amount of study on telomeres.”

Marine enzymes are also starting to gain momentum. Last year, London skin care brand Dr. Bragi’s marine-based products launched in the U.S. The brand’s founder, Jón Bragi, extols his patented marine enzyme, called penzyme, for its ability to penetrate the epidermis deeper than rival enzymes, and withstand heat and activity.

Turning to the structure of the skin, many companies are backing ingredients that encourage the production of glycosoaminoglycans or GAGs. GAGs aid the skin in water retention to keep it moisturized. L’Oréal’s Skin Genesis and Lancôme’s Absôlue range both claim to jump-start GAGs with pro-xylane, a patented plant-derived sugar molecule. Next on the GAG frontier could be N-acetyl glucosamine if NeoStrata, a leading AHA developer, is to be believed. N-acetyl glucosamine is a sugar molecule that’s one of the building blocks of GAGs. “It’s something that we’ll be advancing for antiaging as well as for acne,” says Barbara Green, NeoStrata’s vice president of technology and licensing. “We’ve shown that the use of it topically helps increase skin thickness.”

Under the Microscope

While the new generation of advanced products and ingredients all share lofty claims, they also share another trait: None has been subjected to the rigorous level of testing that drugs go through to win market approval. Without FDA-style protocols, many cosmeceutical tests commissioned by companies are viewed as marketing ploys. They rarely utilize double-blind controlled methods with human subjects and can’t be judged equivalently because they rely on different evaluation techniques.

“The advertising hype is always exaggerated, and the expectations are always higher than they should be,” says Patricia Farris, a dermatologist in New Orleans and a clinical assistant professor at Tulane University. “Because [cosmeceuticals] are not pharmaceuticals, they’re not tested like pharmaceuticals....There’s not a lot of science behind these products.”

Some retailers, particularly electronic retailers, have begun asking companies for proof of claims. “QVC requires a series of testing including dermatological, microbiological assay, microbiological challenge, efficacy, elevated temperature stability and freeze/thaw stability testing as well as testing to confirm percentage claims that may be made on-air and online,” says Eric Christopher, vice president of quality assurance. “We evaluate packaging, labeling and ancillary literature to ensure that it conforms with FDA guidelines and QVC internal quality.”

Some cosmetics companies actually are lobbying for a higher level of regulatory scrutiny. “A number of the smaller, very high quality companies don’t have an appetite for risk, and they’re trying to figure out what they can say and can’t say,” says Jill Alvarez, who heads up the FDA practice at law firm Nixon Peabody in Washington. “The industry would like some clarity. Maybe we need to rethink that line between cosmetics and pharmaceuticals and give the cosmetics companies a little more room.”   

Executives at RéVive, Jan Marini Skin Care, Dr. Jessicu Wu Cosmeceuticals and Innovative Skincare, among others, all consider the possibility of additional regulatory scrutiny a positive. “At this point, it is definitely within the realm of the current cosmeceutical market to produce products that can effect a physiological change in the skin,” says Johns. “We hope in the future that the FDA will have enough manpower to regulate the cosmeceutical industry a bit more than now.

“They need to do more to protect consumers from false claims [and] they need to protect the consumer against ingredients that could be harmful or toxic,” he continues.

Such a standard does exist in Japan, a so-called third regulatory avenue of quasi-drugs for products that mildly impact the body. Writing in the text “Cosmeceuticals and Active Cosmetics,” Kligman indicates that a Japanese classification of products that are “neither pure drugs nor pure cosmetics” as quasi-drugs is reasonable. “They allow cosmetics to include pharmacologically active ingredients, provided that the effects are modest and the products have demonstrated to be safe,” he writes.

Companies have to apply to Japan’s equivalent of the FDA for quasi-drug status, which involves a review period after initial data analysis. Once given the go-ahead to market quasi-drugs, they can label them “medicated” and make specified results claims.

Priori’s Lewis argues that a lot of the cosmeceuticals available in the U.S. might fit into the Japanese quasi-drug category. “You know they’re doing more than cover up, fill in and hide. But do they really require the scrutiny of a drug to be launched in the marketplace?”

Lewis has also attempted a move to standardize ingredient evaluations, proposing EPF, which would measure the free-radical scavenging ability of antioxidants on a scale of 0 to 100. He published an article on EPF in the Journal of Cosmetic Dermatology and has expounded on the subject to the American Academy of Dermatology. “You can’t argue about the need,” says Lewis, who likens EPF to SPF. “It might take 30 years to catch on, but I’m hoping it won’t take that long.”

Of course, many are happy to maintain the status quo. “The right way for the cosmetics industry to be regulated is to allow consumers to have the best cosmetics products under the best timing,” says Lauren Thaman, global director, P&G Beauty Science. “These are not pharmaceuticals. We are changing the appearance of the skin. We are not looking at disease-state skin.”

An act of Congress would be necessary to substantially revise the legal definitions of cosmetics and drugs that inform the FDA. Under the current administration, the FDA, which didn’t respond to a request for comment, has given no signs that it will give cosmeceuticals additional oversight.

It has made decisions, however, that can be instructive to cosmeceutical firms, reproving companies with claims that stretch the cosmetics boundaries. Jan Marini Skin Research found itself in the FDA’s crosshairs with a product called Age Intervention Eyelash Conditioner. The product contained bimatoprost, an active ingredient in the glaucoma drug Lumigan, which is sold in the U.S. by Allergan. But it was Marini’s claim that the product caused eyelashes to grow—and not the inclusion of the ingredient itself—that provoked FDA action.

Marini says the claim was incorporated in the term “eyelash growth factor,” which she used to describe the ingredient. “They [FDA] wrote that it was a drug claim and therefore we were a new, unapproved drug.”

The product was taken off the market in January, following an FDA seizure last year of thousands of units with a retail value of around $2 million. Marini was left confused. “The public might think, ‘This company is trying to be an outlaw.’ That’s not the case,” she says. “It is an area that’s so incredibly murky. If you look at [many cosmetics] ads, they talk about collagen stimulation, collagen bundles. It’s all one big drug claim. Who’s going after them?”

Over the last three years, the FDA has gone after a handful of companies that have made analogous claims. The agency alerted Freedom Plus Corp., which markets Nano Copper Facial Spray, and BioForm Medical, responsible for Cutanix skin care, that their products were being promoted with therapeutic rationale that would designate them as drugs, pointing out several phrases, including “facilitates the increased growth of collagen” and “anti-inflammatory benefits which reduce redness and irritation” that crossed the divide. Fusion Brands and StriVectin’s Basic Research have both been chastised for a variety of claims, notably those that advertised their products as improvements on Botox. After the FDA’s warning, StiVectin’s “Better than Botox” slogan was punctuated with a question mark.

The gray area between cosmetics and drugs is not likely to turn black and white soon, with products becoming more sophisticated, not less. And there’s little doubt that at least some are a cut above their inert ancestors. But it is consumers, not labs, who make the ultimate decision on that effectiveness. Opening their wallets ever wider, they’ve given cosmeceuticals the green light. “We are pretty vain,” concludes Bright. “We will pay anything to look better. It is true.” And it appears to be true even if the scientific proof falters.

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