Vol. 5 • Issue 3 • Page 24
If, as the ancient proverb states, the eyes are the "windows to the soul," then it only follows that people would want to beautify them.
Now, science is developing ways for people to create more beautiful drapes.
With the FDA-approval of Latisse® in December, physicians have a prescription that can elongate and thicken patients' eyelashes, providing yet another complement to Botox and other cosmetic approaches.
Sharing the popularity of this product, a number of other eyelash products purport to lengthen and thicken eyelashes and brows. Some of these companies use similar ingredients as Allergan-a move that has the company pursuing patent infringement lawsuits.
Despite the litigious backdrop of eyelash enhancement product development, physicians who promise the pearls of long
lashes have everything to gain. In a celebrity culture where women spend hundreds of dollars for eyelash extensions, a product that can actually grow eyelashes promises immense value-to both the patient and physician.
Accidental Discovery
To appreciate where the field is now, we must first understand its humble and somewhat unexpected beginnings. Like many medical breakthroughs, eyelash enhancement had its beginnings as an accidental discovery. In the late 1990s and early 2000s, several glaucoma medications
that reduced intra-ocular pressure had an unforeseen benefit. Patients using the drops noted eyelashes that grew in longer, thicker and darker. Of course, there was a catch that prevented this discovery from becoming a slam-dunk cosmetic drug right away: The drug also darkened the iris in some patients.
Researchers learned that prostaglandin analogs, ingredients within the glaucoma medication, were spurring eyelash growth. Prostaglandin analogs are a type of molecule found in several medications in this class of drugs, including latanoprost (Pfizer Inc.'s Xalatan), unoprostone isopropyl (not currently available as a prescription in the U.S.), bimatoprost (Allergan Inc.'s Lumigan), and travopost (Alcon Laborotories' Travatan).
Scientists theorized that alterations could be made to these glaucoma medications to make them suitable for cosmetic use. A new formulation might lengthen lashes without lowering eye pressure or darkening the iris if the compound was applied only to the base of the lashes.
After several years of development, Allergan formulated an application method to deliver the formula to the eyelashes, while safely keeping it out of the eye. The company conducted new clinical trials on the prostaglandin analog bimatoprost. In December, the company received FDA approval for the new indication of treatment for hypotrichosis of the eyelashes. The results of the study were "striking," according to Dee Anna Glaser, MD, who was a principal investigator in the trial.
Study Findings
Two hundred seventy eight healthy adult patients with baseline minimal or moderate eyelash prominence were randomized to apply either bimatoprost or a placebo vehicle once daily for 16 weeks.1Participants were instructed to carefully apply one drop of study medication to a disposable single-use-per-eye applicator and brush along the upper eyelid margin once daily in the evening.
The study used a number of measures of efficacy, including digital image analysis software to evaluate change in eyelash length, thickness/fullness and darkness.
At the end of 16 weeks, participants using bimatoprost experienced a mean increase in eyelash length of 1.4 mm, while those using the vehicle experienced a mean 0.1 mm growth. Those using bimatoprost had a mean change in progressive eyelash thickness/fullness of 0.71 mm, while those in the vehicle group had a mean increase of 0.06 mm. The bimatoprost group showed an average 18 percent increase in darkness, while the vehicle group had an average 3 percent increase.
The study also showed that bimatoprost was well tolerated, with no serious negative side effects reported. The most common adverse events observed in the trial included eye redness (3.6 percent), itchy eyes (3.6 percent) and skin hyperpigmentation (2.9 percent).
This positive safety profile was crucial for the drug to be approved for cosmetic reasons. A patient's safety must always supersede her desire for beauty; the study showed that the designated application method successfully met this criteria. When a small amount of bimatoprost is applied to the eyelids only, it does not have the same lowering effects on eye pressure as when it is applied in drop form to the eye directly.
The reduced concentration combined with the new application method of bimatoprost also avoided another unwanted side effect-iris hyperpigmentation. No study participants had the darkening eye color that some glaucoma patients experienced when applying bimatoprost directly to the eye.
Dr. Glaser points out that even among patients who do use bimatoprost drops, the percentage that experience increased iris pigmentation is low-between 1 and 3 percent. "But with that being said, I do warn my patients that (darkening of the iris) hasn't been reported, but it could happen with this chemical," she says.
Ellen Marmur, MD, chief of the division of dermatologic and cosmetic surgery and assistant clinical professor at the Mount Sinai Medical Center New York, investigated the issue of increased iris pigmentation in a small percentage of patients from the original study on Lumigan.
"Increased pigmentation implies melanocytic stimulation in the iris. My no. 1 concern was whether this led to increased melanoma of the eye, since the uvea of the eye is the primary source of metastatic melanoma when skin is not the source. So far there have been no reports of bimatoprost leading to melanoma," she says.
Richard G. Glogau, MD, another investigator for the Allergan trial, called increased iris pigmentation with Latisse "not statistically impossible but theoretically improbable." The clinical professor of dermatology at the University of California San Francisco said that one patient has experienced a side effect since he began offering Latisse in his private practice in February-but she found it useful.
"One patient had a darkening of the skin at the base of her eyelash, but she didn't find it objectionable because that's were she puts her eyeliner," he says.
Patents & lawsuits
Currently, bimatoprost is the only prostaglandin analog approved by the FDA to induce eyelash growth. However, Allergan was not the first company to develop an eyelash enhancement product containing bimatoprost. In 2005, Jan Marini Skin Research Inc. debuted the first eyelash enhancement formula, available through physicians and med-spa professionals.
Although the exact ingredients of Jan Marini Eyelash were classified as proprietary information, the company acknowledged that the formulation contained bimatoprost. Skeptics questioned how a cosmetic could produce such dramatic physical changes. Before long, the FDA echoed these sentiments, and raised regulatory concerns with the product, calling it an "unapproved and misbranded drug."
Jan Marini immediately stopped sales of Eyelash and embargoed the remaining supplies in a warehouse. The company released a new formulation that did not contain bimatoprost, called "Eyelash Conditioner." Marini also softened claims about the new product so that it only promised to make eyelashes "appear fuller," thus avoiding wording that would classify it as a drug. Despite the new formulation, the FDA seized the remaining Eyelash products from Marini's warehouse.
In Nov. 2007, Allergan filed a patent infringement lawsuit against Jan Marini and several competitors that were using prostaglandin analogs in their products.
Some criticized Allergan for trying to clear the market of competition before repackaging Lumigan and launching it for its own eyelash enhancement product.
However, at the International Master Course on Aging Skin in January of this year, Allergan's CEO, David Pyott, issued this warning: "We own every prostaglandin analog that exists through 2022," he said. "We'd rather sell you the product. We don't want to be in litigation."
Susan Lin, MD, creator of MD Lash Factor, one of the products included in the suit, said that she understood the reason for Allergan's legal action against products containing bimatoprost, but not against products containing any type of prostaglandin analog.
"Who can possibly claim to own an entire class of molecules in the past, present and future? We created a brand new prostaglandin molecule, a novel prostaglandin analog that the FDA reviewed," she says.
Although MD Lash Factor was the only product in the suit to have a double-blind clinical study published in a peer-reviewed journal,2Lin says she had to make the business decision to reformulate the product in the United States, Canada and the EU without prostaglandin analogs because she could not afford to fight a $3 billion corporation.
Allergan dismissed legal actions against Jan Marini Skin Research Inc., MD Lash Factor, and other companies after they agreed to cease distribution of their products containing prostaglandin analogs, but still has patent infringement litigation pending against several manufacturers.
In July, Athena Cosmetics Inc. maker of RevitaLash Eyelash Conditioner, filed a countersuit against Allergan, alleging violations of federal antitrust law, federal trademark law and federal unfair competitiong law.3The intensity of these legal battles implies good news for physicians and patients-the products work.
An ironic consequence of the lawsuits is that they may actually contribute to the growth of competing companies. Rob Trow, CEO of Rocasuba, which distributes the eyelash enhancement product RapidLash, said that all of the litigation and media speculation has created a buzz.
"The desire for beautiful eyes has been at the forefront of the cosmetic industry since the days of Cleapatra," says Rob Trow, CEO of Rocasuba, which distributes an eyelash enhancement product, known as RapidLash. "And Allergan's advertising campaign and even their litigation has created an increased sense of interest [in our product]."
The Future
Since the FDA granted Latisse approval in December, patient response has been positive. Physicians report that all age groups are using the product, with women ages 35 and up comprising the largest patient demographic.
"I have rarely seen any topical medication embraced so enthusiastically," said Dr. Glogau. He said he was surprised to learn how passionate women are about their eyelashes. He believes that women will begin to incorporate eyelash enhancement into their regular beauty regime."The first feature people look at is eyes," says Dr. Glaser, "So having them look great is one of the most important aspects of appearance."
Dr. Marmur said that although she doesn't market Latisse, patients have been calling her to ask for it.
Although there are more than 20 products that claim to enhance eyelashes on the market, Dr. Glaser says that most of them are just glorified mascaras or conditioners. Others claim to be "all natural" but may actually contain some type of prostaglandin analog.
Although Allergan now owns the patent for all prostaglandin analogs for the purpose of inducing eyelash growth, these products may remain on the market throughout the duration of their patent infringement lawsuit-and beyond depending on what the courts find.
Pursuing Other Avenues
Dr. Lin also sees plenty of room for improvement on the currently approved product. For example, Dr. Lin said that when creating a new formula for MD Lash, she discovered that certain peptides could induce the hair follicle into anaphase in the same way as prostaglandins.
"Because we don't completely understand the way that prostaglandin analogs function, I tested other peptides that function similarly and we discovered certain naturally found chemicals that also induce hair growth," she says.
Her new formula is part of the "second generation" of non-prostaglandin eyelash enhancement, and it performed similarly in a small clinical study without posing the risk of eyelid pigmentation, she says. Jan Marini also released a prostaglandin-free formula that uses a proprietary peptide, which the company says has shown impressive results.
Until Allergan's patent infringement lawsuit is settled, Latisse remains the only FDA-approved eyelash enhancement product on the market. Since it is available by prescription only, physicians looking to boost their bottom line can easily do so with Latisse. Although its price point (about $120 for a month's supply) may keep its patient demographic in the above-30 range, Dr. Marmur says her usual patients think nothing of it. "They don't bat an eye," she says.
It remains to be seen if either first- or second-generation eyelash enhancement products will generate yet another serendipitous product-one to induce scalp hair growth. Dr. Lin said that she has already patented a technology that uses both prostaglandins and peptides to do so and is currently working on launching the product.
Dr. Glaser believes that prostaglandin analogs will be studied for inducing scalp growth in the future, but she said that the depth of the hair bulb in the scalp poses difficulties for a topical medication to penetrate. Dr. Glaser said that eyebrow hair growth is a current off-label use that has been successful in many patients.
Currently, more studies are being conducted to evaluate the efficacy of prostaglandin analogs in chemotherapy and alopecia areata patients.
At press time, the FDA sent a letter to Allergan warning the company about misleading information in promotional materials and the Latisse Web site. The FDA has asked Allergan to discontinue use of those materials.
One thing is true: The future looks lush for eyelashes.
References
1. Accessed via http://www.fda.gov/ohrms/dockets/ac/08/briefing/2008-4397b1-03-FDA.pdf
2. Eyelash enhancement properties of topical dechloro ethylcloprostenolamide, Isaac Choy, Susan Lin. Journal of Cosmetic and Laser Therapy: formerly Journal of Cutaneous Laser Therapy, 1476-4180, Vol. 10, Issue 2, pgs. 110 - 11.
3. U.S. District Court, Central Division of California (1) SACV 07-1316 (2) SACV 09 0328.
Nicole Woods is a freelance writer based in Brigantine, N.J.
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