Oral Rosacea Treatment May Be Available Soon

CollaGenex Pharmaceuticals, Inc. (NASDAQ:CGPI) announced today 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."
Approximately 25 million adults in the EU suffer from rosacea. Rosacea affects primarily the face and is characterized by the appearance of inflammatory lesions (papules, pustules and nodules), erythema (skin redness) and telangiectasia (spider veins). If allowed to progress to a moderate to severe condition, rosacea can cause itching, pain and thickening of the skin.
CollaGenex Pharmaceuticals, Inc. is a specialty pharmaceutical company currently focused on developing and marketing proprietary, innovative medical therapies to the dermatology market. CollaGenex's professional dermatology sales force markets Pandel(R), a prescription topical corticosteroid licensed from Altana, Inc., Alcortin(TM) (1% iodoquinol and 2% hydrocortisone), a prescription topical antifungal steroid combination, and Novacort(TM) (2% hydrocortisone acetate and 1% pramoxine HCl), a prescription topical steroid and anesthetic. Alcortin and Novacort are marketed by the Company under a Promotion and Cooperation agreement with Primus Pharmaceuticals, Inc. In addition, CollaGenex has filed an NDA for Oracea(TM), the first systemic compound for the treatment of rosacea, which is currently under evaluation by the FDA, and is conducting a 300-patient, Phase II dose-finding study to evaluate its second dermatology candidate, incyclinide, for the treatment of acne. CollaGenex also currently sells Periostat(R), which the Company developed as the first pharmaceutical to treat periodontal disease by inhibiting the enzymes that destroy periodontal support tissues and by enhancing bone protein synthesis, and Atridox(R), Atrisorb FreeFlow(R) and Atrisorb-D FreeFlow(R), which are products of QLT Inc., the successor to Atrix Laboratories, Inc., for the treatment of adult periodontitis.
Research has shown that certain tetracyclines can be chemically modified to retain non-antibiotic properties that may make them effective in treating diseases involving inflammation and/or destruction of the body's connective tissues. CollaGenex is evaluating various chemically modified tetracyclines (so called "IMPACS" compounds because they are Inhibitors of Multiple Proteases And CytokineS") to assess whether they are safe and effective in these applications. The Company has a pipeline of innovative product candidates with possible applications in dermatology and other disease states. In addition, CollaGenex has acquired the Restoraderm(R) technology, a unique, proprietary dermal drug delivery system, and plans to develop a range of topical dermatological products with enhanced pharmacologic and cosmetic properties.
To receive additional information on the Company, please visit our Web site at www.collagenex.com, which does not form part of this press release.
Statements in this press release, including statements regarding future revenues, gross profits, margins, operating expenses and any other statements about management's expectations, beliefs, goals, plans or prospects, may constitute forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. CollaGenex' actual results could differ materially from those stated or implied in forward-looking statements due to a number of factors, including those factors contained in CollaGenex' most recent Annual Report on Form 10-K for the year ended December 31, 2004 and the most recent Form 10-Q for the Quarter ended September 30, 2005 under the sections "Additional Factors That May Affect Future Results" and "Additional Risks That May Affect Results" as well as other documents that may be filed by CollaGenex from time to time with the Securities and Exchange Commission. Forward-looking statements include statements regarding CollaGenex' expectations, beliefs, intentions or strategies regarding the future and can be identified by forward-looking words such as "anticipate", "believe", "could", "estimate", "expect", "intend", "may", "should", "will", and "would" or similar words. CollaGenex assumes no obligations to update the information included in this press release or revise any forward-looking statements, whether as a result of new information, future events or otherwise.

Topical Therapies For Rosacea

Medical treatment of rosacea with emphasis on topical therapies.Del Rosso JQ.Department of Dermatology, University of Nevada School of Medicine, Las Vegas, Nevada, USA.Due to the development and release of newer topical rosacea formulations, the diagnosis and treatment of rosacea has received renewed attention over the past 3-5 years both in the literature and at medical symposia.
Rosacea is a very common facial dermatosis. In the US, rosacea is estimated to affect 14 million people, predominantly adults with approximately 60% of cases diagnosed before the age of 50. A frustrating aspect of rosacea is it's inherent chronicity punctuated with periods of exacerbation and relative remission.
 A variety of rosacea subtypes have been identified which correlate with the patients rosacea clinical presentation. Although the pathogenesis of rosacea is poorly understood, multiple topical rosacea agents are available. The efficacy of topical therapy for rosacea relates primarily to reduction in inflammatory lesions (papules, pustules), decreased intensity of rosacea erythema, a reduction in the number and intensity of flares and amelioration of rosacea symptoms, which may include stinging, pruritus and burning.
The list of main topical rosacea treatments utilised for the treatment of rosacea include metronidazole, sulfacetamide-sulfur, azelaic acid and topical antibiotics (clindamycin, erythromycin). Depending on the severity at initial presentation, topical therapy may be combined with systemic antibiotic rosacea therapy (e.g., oral tetracycline derivative). Newer choices primarily involve improved vehicle formulations, which demonstrate favourable skin tolerability and cosmetic elegance

Getting FDA Approval For New Treatments

Although the cause of rosacea is unclear and is still under scientific investigation, there has been an explosion of new products -- many available without a prescription -- that imply they may help rosacea. How can rosacea patients know whether such claims have merit?
"In the case of prescription drugs, it is required by law that they undergo clinical studies to demonstrate safety and effectiveness, and the results must be reviewed and approved by the Food and Drug Administration (FDA)," said Dr. Jonathan Wilkin, former director of the FDA's Division of Dental and Dermatologic Products. Advertising for these products -- unlike others -- can be readily identified because it must include extensive clinical information, usually shown in small type, about what the drug is used for, potential side effects and other information.
"While the FDA also monitors nonprescription drugs, I know of none that has been approved as a new drug to specifically treat rosacea," Dr. Wilkin said.
On the other hand, he noted that certain skin-care products may be used for cleansing or to potentially calm inflammation, and that green or yellow makeup can reduce the appearance of redness. "When it comes to products for skin care and cosmetic use, a patient's best bet may be to ask their physician for a recommendation best suited to their individual condition," Dr. Wilkin said.

Grants For Rosacea Research

On the 11th of January 2006, the NRS announced that it has awarded 5 more grants for Rosacea Research."We are very pleased that a growing number of high-quality research proposals are now being received," said Dr. Jonathan Wilkin, chairman of the society's medical advisory board, which reviews each grant application and selects for funding those believed most likely to yield important results. "As this program continues to expand, we are optimistic that it will lead to significant advances in the management of this poorly understood disorder and its potential prevention or cure."
Martin Steinhoff, M.D., and colleagues, of the University of Muenster in Germany, received a $25,000 grant to pursue their theory that the protein endothelin-converting enzyme-1 (ECE-1) may regulate vascular function and nerve-caused inflammation in the skin, and thus be involved in the pathophysiology of rosacea. Their study will attempt to define the expression and distribution of the four ECE-1 isoforms in both normal and rosacea tissue, which may lead to new treatments for rosacea.
Richard Granstein, M.D., chairman of dermatology at Cornell University, and colleagues received a $25,000 grant to further their previous research, which found that substances that activate endothelial cells through P2 cell receptors cause the release of factors that promote inflammation. Their new study will focus on which P2 receptors are affected, and whether inhibiting these substances in vitro may facilitate the discovery of new rosacea treatments.
Richard Gallo, M.D., chief of the division of dermatology at the University of California, San Diego, and Kenshi Yamasaki, M.D., of the Veterans Medical Research Foundation, received a $25,000 grant to continue previous research, which found that individuals with rosacea have an overabundance of a natural antibiotic called cathelicidins. Additional research may show that abnormal regulation of cathelicidin production leads to rosacea, which in turn could lead to new therapeutic approaches.
Yaxian Zhen, M.D., and Albert Kligman, M.D., of the University of Pennsylvania's department of dermatology, will use their $25,000 grant to develop objective, quantitative assessments of rosacea using a variety of equipment. They note that these non-invasive methods would provide a means by which to measure the presence and severity of rosacea's symptoms, perhaps identify new ones, and gauge their presence and severity after treatment.The instrumentation includes scanning laser Doppler imaging, optical coherence tomography, confocal microscopy, specialized digital photography, colorimetry by chromometer and surface (nonsurgical) biopsy. Skin hydration would be measured via an electrical conductance device and a capacitance measuring device, and the skin's topography studied by a fringe projection device.
Payam Tristani-Firouzi, M.D., assistant professor, and Nancy Samolitis, M.D., visiting professor, of the University of Utah's department of dermatology, were awarded $23,600 to examine the effect of pulsed dye laser (PDL) and intense pulsed light (IPL) treatment of rosacea to determine whether, in addition to reducing the amount of blood vessels, these procedures produce structural and biologic changes in the skin.
The Rosacea Research Foundation donated $16,065 to the NRS toward the funding of this study.
"Because the etiology of rosacea is unknown, a high priority in awarding grants is given to studies relating to its pathogenesis, progression, mechanism of action, cell biology and potential genetic factors. Proposals relating to epidemiology, predisposition, quality of life and relationships with environmental and lifestyle factors may also be considered."

Theory of Rosacea

Rosacea could be defined as a genetic abnormality within the vascular structure, could it not? Under pressure it results in the vascular damage that leads to rosacea symptoms. It seems that many are interested in discovering what this genetic flaw is all about and how to correct it (ie with gene therapy).

But I began to wonder more about what causes this 'pressure'. For some it can bought on drugs, others by environmental factors, and it seems that many develop rosacea as a result of some underlying exaggeration of thermo-regulation. This last one is me all over. I have been getting Chilblaines all winter on my fingers and toes, yet my face flushes red hot to the slightest increase in heat. It seems that my body is totally over reacting to thermal stimuli, and I speak to MANY people who consider themselves in the same boat.

Hormonal maybe? A result of an allergy? Imo, if we could correct this then we would rid ourselves also of the superficial symptoms. Take this for example: I read a while back about a particular disorder (I forget which) which resulted in heavy duty facial flushing. Apparently non rosaceans were showing signs of rosacea before too long - their healthly facial blood vessels were buckling under the pressure.

Consider another example, menopausal women - I know women who've shown no sign of rosacea right up until menopausal hot flashes started. Then within a few short years they we well in mild rosacea (sometimes worse). Is it the because the EVERYONE has a breaking point? But most people never reach that point. For us, some other issues combine with our low 'breaking point' and cause us to develop the rosacea vascular damage.