Oracea May Become First Oral Rosacea Treatment

CollaGenex Pharmaceuticals, Inc. (NASDAQ:CGPI) announced February 27 that a Marketing Authorization Application (MAA) for Oracea(TM), has been filed with the United Kingdom's Medicines & Healthcare Products Regulatory Agency (MHRA). The UK will act as reference member state in this decentralized procedure. The MAA for Oracea was submitted to the MHRA on February 24, 2006. A New Drug Application for Oracea was filed with the U.S. Food and Drug Administration in August 2005 and has been given a PDUFA date of May 31, 2006. If approved, Oracea will be the first orally administered, systemically delivered drug developed to treat rosacea.

The MAA was based primarily upon the safety and efficacy results of two Phase 3, double-blinded, placebo-controlled clinical trials for Oracea(R). These studies enrolled a total of 537 patients in 28 centers across the U.S. In the two studies, patients receiving Oracea experienced a 61% and 46% mean reduction in inflammatory lesions compared to 29% and 20%, respectively, in patients receiving placebo. The differences were clinically and statistically highly significant (p = less than 0.001 in each study). Side effects of the drug were similar to placebo.

"This is an important step towards maximizing the worldwide opportunity for Oracea," said Colin Stewart, president and chief executive officer of CollaGenex. "If approved by the MHRA, we intend to seek registration for Oracea in other countries of the European Union."

Ocular Rosacea Picture May Worsen In Winter

If you're bothered by irritation, burning or a gritty feeling and redness in your eyes, you're not alone. Winter can bring a host of special challenges for rosacea patients, and the effects of dry eye head the list for many.

"Millions of people suffer from dry eye, and it accounts for 17 percent of all ophthalmologic visits," said Dr. Marian Macsai, chairman of ophthalmology at Northwestern University. "We definitely see more of it during the winter months because of the dryness of the environment, and it often accompanies rosacea."

Dr. Macsai explained that dry eye is either an inability to produce natural tears, or occurs because the oily (lipid) layer in the tear film is unhealthy or incomplete. A dry and windy environment can also cause more rapid evaporation of the aqueous layer of tears. In patients with eye (ocular) manifestations of rosacea, this condition is frequently made worse by blockage of the meibomian glands at the base of the eyelashes, which produce the lipids that hold the moisture on the surface of the eye.

In a recent National Rosacea Society survey of 1,780 rosacea patients reporting ocular symptoms, 95 percent said their eyes had felt dry, gritty or irritated, yet only 28 percent said they had been diagnosed with ocular rosacea.

"If the symptoms of ocular rosacea persist, it's a good idea to make an appointment with an ophthalmologist," said Dr. Macsai. Left untreated, patients with severe ocular rosacea could endure potentially serious consequences, such as scarring within the eyelid or corneal damage that could lead to decreased vision.

For mild symptoms, Dr. Macsai advises patients to use a humidifier or other means to raise the humidity at home or in work environments. She also noted that artificial tears are available at drugstores to moisturize the surface of the eye.

For her rosacea patients with dry eye problems, Dr. Macsai also emphasizes good eyelash hygiene to minimize blockage of the meibomian glands. She suggests a daily eyelash shampooing that can be performed at the end of a morning shower. Place a drop of baby shampoo on a wet washcloth and carefully rub it onto a closed eye to create a slight lather. Rub the washcloth gently back and forth in a horizontal motion over the upper and lower eyelashes. After shampooing the eyelashes on one eye, shampoo the eyelashes on the other eye.

Then, keeping the eyes closed, put your face under the shower water and rinse off all of the soap until the eyelashes feel squeaky-clean. Gently towel dry. This procedure may also be used in the bath or in front of the sink.

"Your doctor may also prescribe an ointment to rub into your lashes twice a day," Dr. Macsai said. "If any eye symptoms persist or worsen at any time of the year, make an appointment with an ophthalmologist."

Derm Claims Tap Water Dangerous To Skin

Dr. Dennis Gross, a clinical professor at New York University Medical Center, says tap water contains heavy metals that breakdown collagen and lead to wrinkles.

Never fear: Gross has just the answer to those scary heavy metals. He has developed a product that contains chelators, which are an organic solution to the buildup of heavy radicals on the skin.

There are great variations in the content of heavy metals, calcium, and sulfates from one city's water to the next. Gross claims that these elements build up on the skin's surface and cause dermatologic problems such as acne, rosacea, and aging.

"While the water is clearly drinkable, if you are unlucky enough to be exposed to bad water on a regular basis your skin can suffer the same kind of damage, although to a lesser degree, as sitting in the sun with suboptimal protection," says Dr. Gross, associate.

The Physical Discomfort Rosacea

While the effects of rosacea on facial appearance are widely known, the majority of patients also experience physical discomfort, according to a recent survey by the National Rosacea Society.

In the survey of 605 rosacea patients, 93 percent said they experienced at least some physical discomfort due to their rosacea. Among those who experienced discomfort, the most common complaints were burning (72 percent), itching (61 percent), stinging (52 percent) and swelling (41 percent).

Forty percent reported tenderness, while 36 percent said they experienced tightness in their skin. Thirty-one percent had experienced tingling, and 24 percent felt a prickling sensation.

Physical discomfort was experienced most often in the facial regions where rosacea is most commonly found: the cheeks (80 percent), nose (53 percent), eyes (48 percent), chin (40 percent) and forehead (36 percent). Interestingly, a number of rosacea patients reported discomfort in areas beyond the central face, including the ears (18 percent), scalp (20 percent), neck (16 percent) and behind the ears (11 percent).

Seventy-two percent of those surveyed said the discomfort occurred at the same time as the physical signs of rosacea, and an additional 21 percent said there was some correlation. Fortunately, 84 percent reported that medical therapy helped relieve the discomfort associated with their condition.

"The physical pain experienced by many rosacea patients is often under appreciated by others," said Dr. John Wolf, chairman of dermatology at Baylor College of Medicine. "Rosacea patients need to take special care to avoid substances that irritate their skin, along with other triggers that might cause irritation and lead to a flare-up."

IPL Claims To Do It All But Is It Too Good To Be True?

Patients seek treatment that offers a return to a more youthful appearance through restoration of even color and smoothness, relief from pigmentary sun damage, and the redness and flushing associated with rosacea. In addition, this patient group requires treatments that are short and pain-free, and allow immediate return to all activities.

Following more than 20 years of treatment of vascular lesions using the pulsed dye laser, a new laser-like intense pulsed light (IPL) device was developed that treats these conditions with success and answers the essential lifestyle criteria when used in a carefully administered program. This new IPL skin rejuvenation technique called Photofacial now has a clinical history of many treatments with excellent patient success.

IPL differs from laser light in that, rather than monochromatic single wavelength, IPL emits a non coherent, broad spectrum light. The Luxury or Supreme device made Coslux (www.coslux.com) used in the Photofacial procedure emits a spectrum extending from 530nm to 1200nm. To customize the light energy delivery for a given procedure, the operator employs a light guide, of designated wavelength, below which the spectrum is selectively eliminated.

The IPL system, as used in the Photofacial procedure, conforms to the principle of selective photothermolysis. For dilated vessels, as seen in patients with sun damage and rosacea, the light energy with high absorption by hemoglobin and oxyhemaglobin reaches the dermal capillary bed and selectively destroys the abnormal vessels.

The operator controls all aspects of the light pulse, including cutoff wavelength (nm), energy level (Joules/cm2), pulse duration (milliseconds), pulse pattern (single, double, or triple), and delay time between pulses (milliseconds). This allows for precise control of light energy, which in this procedure is utilized for customization for skin type, procedure progress, and other variables. All controls are computer driven, and the system houses a patient database that automatically records the parameters of the treatment and treatment history for each patient.

Rosacea is a chromic skin disorder affecting the face, characterized by redness and telangiectasias, and is punctuated by episodes of inflammation with papules, pustules, and swelling. The underlying causes of rosacea have not been elucidated yet. There are four basic stages through which rosacea sufferers may progress: pre-rosacea, mild, moderate, and severe forms. Pre rosacea refers to the stage where a person flushes or blushes to a stimulus, but returns immediately to normal when the stimulus is removed. The progression of pre-rosacea to bouts of flushing and blushing that do not dissipate for hours or days is now considered to be directly related to micro vascular dysfunction or damage. In support of this, leading dermatologists Dr Neumann and Dr Frithz recently reported that biopsies of vascular lesions from rosacea patients demonstrated moderate to severe damage of endothelial and smooth muscle cells. In addition, these same biopsies showed evidence of abnormal fusion of capillaries and angiogenesis. Taken together, rosacea-related alterations in endothelial cells, vascular smooth muscle, formation of new inflammatory shunt vessels, and angiogenesis could explain why the rosacea-related red face, flushing, and blushing worsens over time. In effect, it is plausible that alterations in micro vascular structure and function allow for more intense bouts of blood flow and inflammation, resulting in even more micro vascular damage — a vicious and progressive cycle. Therefore, therapy should be centered around the removal of damaged and dysfunctional micro vessels such that new thicker walled micro vessels with normal plump endothelial cells are laid down. Previous treatment of the acute inflammatory episodes have consisted of avoidance of heat, cold, sunlight, alcohol, and stress. Physicians have used tetracycline’s, dapsone, erythromycin, chloramphenicol, metridonazole, clonidine and Accutane with limited success. Topical treatments with antibiotics, sulfa preparations, and topical steroids have also been used. Indeed, steroid use ultimately compounds the problem by causing more reddening, flaring, and atrophy. None of these treatments remove the abnormal vessels. Electrocautery treats only those larger visible vessels, and not without pain, bleeding, and frustration of both practitioner and patient.

It is extremely rare for an IPL patient to experience purpura. Following treatment, the patient may have mild redness and swelling overnight, but daily activities are not affected, and many patients can return to work within a few hours.

IPL has demonstrated an improvement in fine lines and wrinkles, as well as reduction in pore size, possibly due to new collagen deposition in the dermis. This technique is not effective for treatment of sagging skin which is normally treated surgical techniques. IPL has also been used effectively to treat psoriasis of the face, to reduce erythematic following laser skin resurfacing, and to treat acne scarring.

The Photofacial technique is a proprietary treatment protocol. It consists of a series of IPL treatments, usually five to six treatments over a period of 4 months. The IPL is performed on the full face.

Two-hundred patients with rosacea were chosen randomly by Coslux and evaluated to determine the overall success with the IPL. Patient satisfaction was high with dramatic improvements. The results of this treatment have been truly remarkable. The most difficult patients to treat were those with Fitzpatrick skin type I who have a long history of sun exposure. In these patients, connective tissue is so fragile that IPL parameters selected for optimal relief of redness may damage the skin, with higher incidence of purpura, swelling, and blistering. In such cases, sub optimal parameters must be used early in treatment until the connective tissue supporting the dermal architecture is strengthened and the target tissue is reduced in size. The standard five treatment program is usually extended in this patient group.

Working with the constraints of the lifestyles of active working patients requiring brief, relatively pain-free facial treatments with little downtime, the IPL skin rejuvenation technique provides superior cosmetic results. Specifically, the treatment offers relief from the redness and flushing symptoms of rosacea, improved smoothness and texture of facial skin, remove age spots, restoration of even color, and a dramatic reduction of fine and wrinkles.

The Role Of Sulfur In The Rosacea Picture

For over two decades, sulfur has been used for the treatment of rosacea, and clinical studies have demonstrated that it is extremely effective in the treatment of rosacea-related papules and pustules. Many dermatologists tailor rosacea treatments to the individual by varying the concentration of sulfur in a given preparation (from 2 percent to 15 percent sulfur). Because rosacea is a chronic disease, treatment must usually be continued for a long period of time. For this reason there was interest in a topically administered treatment that would be as effective as orally administered drugs such as antibiotics. To date, many medical physicians use topical sulfur as their primary anti-rosacea treatment. In a double-blind clinical study of 40 rosacea patients, these physicians found that rosacea-related papules and pustules responded much better to topical 10 percent sulfur than to oral antibiotics. More specifically, they found that with four weeks of topical sulfur treatment, the average number of papules and pustules dropped significantly (from 213 pimples before treatment to 17 pimples after treatment), that this clearing was much better than that attained by treatment with oral tetracycline. In a separate series of clinical studies, similar results were found by Dr. Strauss and colleagues.

How to Recognise Rosacea

Pimples of rosacea appear on the face as small, red bumps, some of which may contain pus.
These may be accompanied by the development of many tiny blood vessels on the surface of the skin and persistent redness of the face.

In more advanced cases of rosacea, a condition called rhinophyma may develop. The oil glands enlarge causing a bulbous, enlarged red nose and puffy cheeks. Thick bumps can develop on the lower half of the nose and nearby cheeks. Rhinophyma occurs less commonly in women.

About 50% of people with rosacea have eye involvement. Some rosacea patients experience burning and grittiness of the eyes - a condition known as conjunctivitis. If this condition is not treated, it can lead to even more serious complications for the eyes.