The European Aesthetic Guide Autumn 2009 : Page 1

In 2009 and 2010 pharmaceutical com- pany Merz GmbH & Co. KGaA (Frankfurt, Germany) is planning a major push deeper into the worldwide aesthetic market. The com- pany has a history of compassion for patient needs, as well as innovation in healthcare that spans more than 100 years. Among other long range efforts, Merz plans to strengthen the international aesthetic pipeline with the creation of its own brand of neuro- modulators (botulinum toxin), dermal fillers and standardized, validated scales to grade aging skin. continued on page 3

Merz Expands Aesthetic Product Offerings

Kevin A. Wilson

In 2009 and 2010 pharmaceutical company Merz GmbH & Co. KgaA (Frankfurt, Germany) is planning a major push deeper into the worldwide aesthetic market. The company has a history of compassion for patient needs, as well as innovation in healthcare that spans more than 100 years. Among other long range efforts, Merz plans to strengthen the international aesthetic pipeline with the creation of its own brand of neuromodulators (botulinum toxin), dermal fillers and standardized, validated scales to grade aging skin. Merz Continues Legacy of Innovation and Science in Global Aesthetic Market The Merz legacy began in Germany with founder Friedrich Merz, who in 1911 patented his first invention: a grease-free, water-soluble, pH-neutral base for topical therapies. “In the early years Merz was dedicated to the field of dermatology,” said company CEO Martin Zügel, Ph.D. “We started with skin therapy cream similar to gel technology. We moved on to beauty products in the 1950s and we had one of the first creams on the market, Placentubex, which was considered a sensation.” The Merz beauty heritage was further ensconced as their offerings became household names in Germany by the 1970s. From there, Merz moved into the pharmaceutical business with highly-respected scar treatment products, a blockbuster neurological franchise, more recent dermal fillers and the neuromodulator Xeomin. “We respond to consumer needs, and are constantly researching products that better serve the end user,” he noted. Participation in the aesthetic market is one of the key strategic business segments the company is investing in, according to Dr. Zügel. “Merz has a strong general dermatology business globally, with both over-the-counter and prescription products. We are strategically reinvesting our profits into the growing aesthetic arena with the objective of becoming a leading player,” he said. “Neurotoxin and quality dermal fillers are the key to growth in global aesthetics. With this in mind, Xeomin has recently gained marketing authorization for the treatment of glabellar lines in Germany (under the brand Name Bocouture). This is an entry level product that patients will use as a minimally invasive and possibly preventative measure. The market demographic for this product is getting younger and younger around the globe.” According to Jürgen Frevert, M.D., of Potsdam, Germany, inventor of Xeomin (Bocouture), this neuromodulator consists of only pure active ingredients, with no complexing proteins, which reduces the risk of antibody formation and drug resistance that may complicate future treatment. “Xeomin is clearly a next-generation neuromodulator. It has a very high grade of purity which we believe has the lowest immunogenic potential right now,” he explained. “This becomes even more important if higher or repetitive doses are used. It requires no refrigeration, which makes handling and storage easier.” A major advantage of Xeomin is its similarity to BOTOX Cosmetic from Allergan, Inc. (Irvine, California, U.S.). Both use the same active ingredient, advised Alastair Carruthers, M.D., clinical professor of dermatology at the University of British Columbia (Vancouver, British Columbia, Canada), who, along with his wife, Jean Carruthers, M.D., are probably best known for their pioneering work with neuromodulators in aesthetic medicine. “Preliminary clinical studies show Xeomin and BOTOX are injected similarly, they produce similar effects, and similar unit doses produce clinically equivalent results. Diffusion in the tissue, as well as, adverse events are similar. It must be noted that even a difference of, say, 20% in unit equivalence may not be noticeable by the user, so I’m not saying Xeomin is better than BOTOX or vice versa, only that clinical studies have shown similarity. If I have a 100 unit vial of one product in my hand, it will perform similarly to a 100 unit vial of the other.” Physicians have been using BOTOX Cosmetic worldwide for many years and there is a huge amount of knowledge about its dosing and applications, according to Dr. Jean Carruthers, clinical professor of ophthalmology at the University of British Columbia. With Xeomin, the unit comparison to BOTOX in all published clinical work to date is 1:1. Belotero, Merz’s highly successful range of hyaluronic acid (HA) dermal fillers, is available in several European markets with plans for broader global distribution. Pending FDA clearance, the company expects Belotero to be marketed in the U.S. in 2010. “Belotero is a best-in-class dermal filler product line which, in its different concentrations, can service all relevant tissue targets,” noted Rainer Pooth, M.D., head of clinical dermatology research and development at Merz. “Competing dermal fillers such as Restylane from Medicis (Scottsdale, Arizona, U.S.) are biphasic gels. Belotero is a homogeneous, monophasic gel, with unique density zones. This makes it very safe and tolerable with ideal tissue integration for natural looking results. Pain during implantation is quite low.” There are three products in the line: Belotero Soft, Belotero Basic and Belotero Intense, which is the newest of the three. Basic is for frown lines, forehead lines and perioral lines. Areas such as the décolletage or hands are best served by Belotero Soft, while Belotero Intense works for moderate-todeep lines and general volumization, including lip augmentation. Merz’s newest dermal filler, Novabel, is in a class by itself, according to Berthold Rzany, M.D., Sc.M., of the Klinik für Dermatologie, Allergologie und Venerologie, Charité - Universitätsmedizin Berlin (Berlin, Germany). “This is totally different from existing dermal filler lines,” he said. “Since it’s not a hyaluronic acid based filler there is generally much less swelling, which makes it easier to see results.” The patented, plant-based composition of Novabel is part of the product’s competitive advantage, according to Dr. Pooth. “Novabel is highly purified to minimize foreign body reactions,” he stated. “Research has shown excellent safety in an 18 month study. Novabel provides a natural-feeling result with good tissue integration. There is no downtime so Novabel is truly a lunch time treatment.” Dr. Rzany agreed that Novabel results should persist for 12 months or more. “We do not have the clinical trial results yet, but based on what I have seen, Novabel should last as long as HA or even longer. We’re committed to the science – evidence-based medicine is most important,” he said. Perhaps there is no better example of Merz’s commitment to the science of medicine than the Merz Scales. As part of their kickoff into aesthetic medicine in the U.S. earlier this year, Merz sponsored the development of a series of standardized, validated five point photonumeric scales for grading the process of skin aging. The Merz Scales address the scientific need for standardization, validation and consistency of measurement that contributes to intellectual communication, education and growth of the research community. “Merz took an interest in the greater scientific community and put their weight behind a purely scientific endeavor. That was a phenomenal step for them to take and we are very impressed with Merz for doing this,” said Dr. Alastair Carruthers, who was a lead author of research on these scales, along with Dr. Jean Carruthers. Developed by an international team of top aesthetic physicians, headed by Drs. Jean and Alastair Carruthers – both world renowned luminaries – the Merz Scales are a first-of-its-kind system in aesthetic medicine. “Recent surveys have shown that the popularity of cosmetic procedures in the U.S. has increased phenomenally, well over 400% over the past decade or so, with about two-thirds being less invasive non-surgical procedures,” said Dr. Alastair Carruthers. “This has driven the industry to new heights, and companies are constantly developing new, exciting treatments that are safer and more effective than ever before. However, there is a clear need for standardized scales to measure the aesthetic aging process – statistical measurement tools that are clear, validated and easy-to-use will be useful To researchers and practitioners across the globe.” The first Merz Scales were published in the November 2008 supplement of Dermatologic Surgery (Dermatol Surg 2008 Nov; 34(S2)). In addition to Drs. Alistair and Jean Carruthers, the team of physicians who worked on the scales was drawn from dermatology and plastic surgery. This group included Derek Jones, M.D., board certified dermatologist in Beverly Hills, California, U.S.; Dr. Rzany; Joel Cohen, M.D., board certified dermatologist in Englewood, Colorado, U.S.; Martina Kerscher, M.D., dermatologist in Germany; Timothy Flynn, M.D., board certified dermatologist in Cary, North Carolina, U.S.; Corey Maas, M. D., board certified facial plastic surgeon in San Francisco, California, U. S.; and Gerhard Sattler, M.D., dermatologist in Darmstadt, Germany – all recognized experts in their fields. This team met in August 2007 for the Scale Summit in Montreal, Canada to discuss the development of these scales with members of the Merz research and development team. “We examined the lack of standardized methods to quantify and define the aging process that would transcend global differences in ethnicity,” said Dr. Pooth. “Statistical validation was also necessary to enhance consistency.” In an effort to provide a reasonable scientific basis for standardization, the exhaustive validation process required these nine experts to repeatedly grade carefully selected sets of photographs and statistically compare the grades. Photographs included a variety of ethnic and skin types. Rater comparison was recorded by bubble graph. “These grading tests took several days to complete. We didn’t grade each group of photos once, we tested everyone again the next day to check consistency,” explained Dr. Jean Carruthers. “With our group of experts hailing from around the world and coming from different fields within aesthetic medicine, we feel a certain assurance that physicians worldwide will be able to adequately understand and successfully use the Merz Scales consistently, whatever their specialty or experience level.” This endeavor resulted in a series of five point grading scales. Although each scale is a bit different, experts chose to use five points, going from zero to four, based on a mutually agreed upon set of standards for usefulness. “The scales are stratified with five points, each easily differentiated and well described,” reported Dr. Pooth. The number five was chosen because in addition to including a low point, a midpoint and an endpoint, there isn’t too much room for confusing variability. Also, the scales are limited to covering the span of aging that physicians would most commonly observe in a clinical setting, so skin at an extremely young or old age is not represented. “Many of these scales work for both the at-rest and dynamic phases, or have two components because the upper and lower lips, for example, age differently,” explained Dr. Jean Carruthers. “This system is flexible enough to deal with those issues.” According to Dr. Jean Carruthers, a grading system such as the Merz Scales offers the scientific community a standardized method of intelligently describing and discussing aging skin, which is essential. “The Fitzpatrick Skin Type scale is incredibly useful. It’s an excellent standard for talking about skin color that’s been successfully used for many years now,” she said. “When you consider the enormous Increase in the number of physicians performing aesthetic procedures, it becomes more imperative that we have a standardized method of communication about a subject as large and important to the field of aesthetic medicine as the appearance of aging skin at different areas of the body. The Merz Scales represent a leap forward by facilitating the productive intellectual interpretation and discussion of the subject. They may also become an excellent teaching tool.” “Eventually, the Merz Scales will also help us communicate with patients in every phase of the process, from pure description to management of expectations,” added Dr. Alastair Carruthers. “Our perception of what their lips look like at a given point in time, for example, may be very different from theirs.We will be able to show them pictures of other people for comparison. It will also allow us to describe more accurately what is possible to achieve through various methods. Managing expectations is a major component of successful aesthetic medicine.” Currently, Merz Scales have been developed for the consistent aesthetic grading of brow positioning, crow’s feet, forehead lines, hands, lip fullness and marionette lines. “We actually worked on about a dozen different scales but excluded those we weren’t able to validate. Clearly, more work is needed and we hope to be involved in that,” said Dr. Jean Carruthers. Development of scales for more indications using the same criteria is ongoing and recognition of the Merz Scales by the aesthetic community is growing. “I have received many phone calls about the scales,” said Dr. Alastair Carruthers. “Many are researchers who want advice about using the scales in their projects. Another group is trying to use the scales to create something patients can use on their own. This is truly exciting and there’s no end in sight.” Further work on scales for ethnic minorities and broader areas of the face are also in the works, led by Dr. Pooth. “The goal is to create a set of scales that not only address single-case deficiencies but move into the scope of the full face and even body contouring in the future,” he explained. “That’s why we assembled a best-in-class international panel that includes key opinion leaders from around the world to reflect a truly global perspective on aesthetic medicine as a whole. This is our commitment to the science, research and education, as well as treatment of patients. In the end the patient benefits most.” Although Germany is the home market where all things from Merz begin, the company’s global aspirations are a priority. “We’ve moved these aesthetic products into other German speaking companies first, then globally to Russia, Mexico, the U.K. and Italy. Soon we will have all the major European markets and the U.S. market next year,” Dr. Zügel advised. “Xeomin is already approved in Argentina, Mexico and Canada, for example. “Simply put, these are the three pillars of Merz’s vision: history and heritage, innovative products rooted in science and commitment to service,” Dr. Zügel concluded.

Publication List