At the General Session of the International Association for Dental Research (IADR), which took place from March 13 to 16, 2024, in New Orleans, LA, USA, Dr. Wolff’s research provided several important scientific insights for oral care, particularly regarding the effects of hydroxyapatite (HAP). The scientific symposium focusing on the biomimetic active ingredient and several oral and poster presentations gained significant attention.
Prof. Dr. Bennett T. Amaechi, Dr. Pascal Fandrich, Prof. Dr. Elżbieta Paszynska, Dr. Frederic Meyer, Carlo Cortez, Prof. Dr. Bernhard Ganss and Dr. Joachim Enax at the General Session of the IADR 2024 (from left).
The scientific symposium “Emerging Technologies for Caries Management: The Case for Hydroxyapatite” was a particular highlight with the internationally renowned cariologist Prof. Dr. Bennett T. Amaechi (Department of Comprehensive Dentistry, University of Texas Health, San Antonio, USA) holding the scientific chair. The session offered an in-depth look at the physicochemical properties of HAP, presented by Dr. Joachim Enax (Senior Scientist Oral Care, Dr. Wolff Research), and highlighted the biomimetic mode of action, the ability to remineralize even deeper layers of enamel caries and teeth affected by Molar Incisor Hypomineralization (MIH), as well as the protective effect against acid attacks through the release of calcium ions. Prof. Dr. Elżbieta Paszynska (Department of Integrated Dentistry, Poznan University of Medical Sciences, Poland) presented various clinical studies confirming the caries-preventive properties of HAP. Her remarks sparked great interest and led to a lively discussion about the benefits of HAP as a safe and effective alternative to fluoride-containing toothpastes. To conclude the symposium, Prof. Dr. Bennett T. Amaechi discussed further modes of action of HAP in caries and other dental defects based on various in situ studies.
Presentation of the Latest Findings on HAP
Dr. Frederic Meyer presented data in a lecture showing that HAP toothpaste is significantly more effective in remineralizing teeth with Molar Incisor Hypomineralization (MIH, or chalky teeth) than an adult toothpaste with fluoride. The results point out the potential of HAP to help patients suffering from chalky teeth.
Furthermore, Dr. Joachim Enax and Dr. Pascal Fandrich presented research findings on the properties of various calcium phosphates, especially HAP, and their application in dental care. The comprehensive examination of various calcium phosphates confirms HAP as the best-studied active ingredient, whose effectiveness has been demonstrated in numerous studies for different applications.
Growing Importance of HAP in Dentistry
The presentations and discussions at IADR 2024 clearly reflected the increasing international relevance of HAP in dental research. It was once again evident that alternative active ingredients are needed for caries prevention. The intense scientific discussions and the high interest of the scientific community confirm that HAP is an effective and safe active ingredient in oral care which is already being used in products and benefiting patients.
Research results, studies and papers from the past 40 years on the active ingredient hydroxyapatite can be found in our study database. The study results are accessible without registration.
Dr. Wolff Research presents scientific contributions at the Annual Meeting of the International Association for Dental Research (IADR) from March 13 to 16, 2024, in New Orleans, USA
Special highlight: Scientific symposium on Dr. Wolff Research entitled “Emerging Technologies for Caries Management: the Case for Hydroxyapatite”
At the IADR General Session & Exhibition 2024 in New Orleans, Dr. Wolff will present several scientific contributions focusing on hydroxyapatite as active ingredient in oral care.
One main focus is the scientific symposium with its title “Emerging Technologies for Caries Management: the Case for Hydroxyapatite” which will be conducted in collaboration with the internationally recognized dentist and cariologist Prof. Bennett T. Amaechi (Department of Comprehensive Dentistry, University of Texas Health, San Antonio, USA). The symposium will focus on the properties and applications of hydroxyapatite (HAP) in caries prevention. The speakers Prof. Dr. Elżbieta Paszynska (Department of Integrated Dentistry, Poznan University of Medical Sciences, Poland), Dr. Joachim Enax, Dr. Frederic Meyer (both Senior Scientists at Dr. Wolff Group, Germany) and Prof. Bennett T. Amaechi will present and discuss the chemical and biological properties of HAP and focus on the results of various studies demonstrating the effectiveness and safety of HAP compared to traditional active ingredients in dental care, such as fluoride.
These topics will be further presented in the following agenda items:
Oral Presentation by Dr. Frederic Meyer: Study on the remineralization of molar incisor hypomineralization (MIH) with HAP
Poster Presentation by Dr. Joachim Enax: Calcium phosphates in dental care products with a focus on HAP
Poster Presentation by Dr. Pascal Fandrich: Research findings of Dr. Wolff regarding the abrasiveness of toothpastes and methods for roughness measurement
Personal expert discussions with the speakers at the IADR annual meeting in New Orleans are possible by arrangement and availability. Please direct your inquiries to pr@drwolffgroup.com.
Further long-term clinical study confirms: Hydroxyapatite (HAP) and fluoride are equally effective in cavity prevention [1].
Safe and effective: HAP as a multifunctional active ingredient also suitable as an alternative in cavity prevention
Modern dental care products are demanded to be safe and effective while providing a good feeling in the mouth as well as having a scientifically proven effect. One of the most important tasks of toothpaste and its ingredients includes the prevention of cavities, also known as dental caries. Hydroxyapatite is one such active ingredient that fulfils these criteria [2, 3]. The efficacy of hydroxyapatite has been researched and confirmed in vitro and in situ for a long time [2]. A recently published long-term clinical study shows again that hydroxyapatite is as effective as fluoride in cavity prevention [1].
Clinically proven that hydroxyapatite is safe and effective in cavity prevention
It has been known for some time that hydroxyapatite is effectively preventing dental caries. High-impact clinical randomized double-blind studies confirm the efficacy of hydroxyapatite in cavity prevention, for example in high-risk patients with orthodontic appliances [4] as well as in children [5]. A meta-analysis published in a high-ranking international journal also shows that hydroxyapatite is effective in the prophylaxis of caries [6].
A recently published long-term study conducted according to the highest scientific standards, in which adult subjects brushed their teeth for 18 months with either hydroxyapatite toothpaste or fluoride toothpaste, provides renewed evidence of the effectiveness of this nature-inspired active ingredient [1]. The study was set up with identical compositions of both toothpastes differing only in the main active ingredients hydroxyapatite (proportion comparable to Karex toothpaste) or fluoride (1450 ppm; maximum permissible concentration for adults: 1500 ppm). The results of the study show that toothpaste without fluoride but with hydroxyapatite instead is just as effective and tends to be even better at protecting against caries than conventional dental care. Caries was detected with well-established methods. On the one hand, the tooth surfaces were visually observed for caries detection. On the other hand, the results were verified using an objective caries diagnostic method.
The evidence is thus very clear: hydroxyapatite provides clinically proven cavity prevention, is safe to use for all ages, and does not require warnings or strict regulation unlike fluoride [7]. Canadian health authorities for example have officially recognized fluoride-free toothpaste containing hydroxyapatite as an anti-caries toothpaste based on scientific data and the results of clinical studies.
Hydroxyapatite is safe in dental care
Hydroxyapatite is a biomimetic active ingredient that occurs naturally in bones and teeth (dentin and enamel). As an endogenous substance, it is safe for use in cosmetic products and has a multifunctional effect, not only as a caries protector [2, 3]. Thus, hydroxyapatite improves gum health and has been shown to be the best agent to prevent pain-sensitive teeth and reduce pain according to meta-analyses [8, 9]. In addition, hydroxyapatite is safe if swallowed and is not subject to quantity limits like fluoride.
Other research results from the past 40 years on hydroxyapatite as active ingredient in dental care can be found in our free study database. The study results can be accessed without registration.
Resources [1] May, B. Amaechi, H. Limeback, A. Hernik, J. Otulakowska-Skrzynska, A. Krahel, I. Kaminska, J. Lapinska-Antonczuk, E. Stokowska, M. Gawriolek, Caries-preventing effect of a hydroxyapatite-toothpaste in adults: A 18 months double-blinded randomized clinical trial, Front. Public Health 11 (2023).
[2] J. Enax, H.O. Fabritius, K. Fabritius-Vilpoux, B.T. Amaechi, F. Meyer, Modes of action and clinical efficacy of particulate hydroxyapatite in preventive oral health care − state of the art, Open Dent. J. 13 (2019) 274-287.
[3] M. Epple, Review of potential health risks associated with nanoscopic calcium phosphate, Acta Biomater. 77 (2018) 1-14.
[4] U. Schlagenhauf, K.-H. Kunzelmann, C. Hannig, T.W. May, H. Hösl, M. Gratza, G. Viergutz, M. Nazet, S. Schamberger, P. Proff, Impact of a non-fluoridated microcrystalline hydroxyapatite dentifrice on enamel caries progression in highly caries-susceptible orthodontic patients: A randomized, controlled 6-month trial, J. Invest. Clin. Dent. 10 (2019) e12399.
[5] E. Paszynska, M. Pawinska, M. Gawriolek, I. Kaminska, J. Otulakowska-Skrzynska, G. Marczuk-Kolada, S. Rzatowski, K. Sokolowska, A. Olszewska, U. Schlagenhauf, T.W. May, B.T. Amaechi, E. Luczaj-Cepowicz, Impact of a toothpaste with microcrystalline hydroxyapatite on the occurrence of early childhood caries: a 1-year randomized clinical trial, Sci. Rep. 11 (2021) 2650.
[6] H. Limeback, J. Enax, F. Meyer, Biomimetic hydroxyapatite and caries prevention: a systematic review and meta-analysis, Can. J. Dent. Hyg. 55 (2021) 148-159.
[7] F. Meyer, J. Enax, B.T. Amaechi, H. Limeback, H.-O. Fabritius, B. Ganss, M. Pawinska, E. Paszynska, Hydroxyapatite as remineralization agent for children’s dental care, Front. Dent. Med. 3 (2022).
[8] H. Limeback, J. Enax, F. Meyer, Clinical Evidence of Biomimetic Hydroxyapatite in Oral Care Products for Reducing Dentin Hypersensitivity: An Updated Systematic Review and Meta-Analysis, Biomimetics 8 (2023) 23.
[9] M.L. Hu, G. Zheng, H. Lin, M. Yang, Y.D. Zhang, J.M. Han, Network meta-analysis on the effect of desensitizing toothpastes on dentine hypersensitivity, J Dent 88 (2019) 103170.
From June 14 to 16, leading scientists, dermatologists and hair research experts met at the 20th European Hair Research Society (EHRS) Meeting in Sheffield, England. Dr. Erik Schulze zur Wiesche, head of Dr. Wolff’s medical research department, presented the latest results on caffeine and dimethylglycine used for alopecia.
Caffeine is the most studied phytochemical for female and male alopecia. Over the past two decades, a large number of studies have shown that the active ingredient can prevent hair loss. New studies already submitted for publication prove that the effect of caffeine can be enhanced by the active ingredient dimethylglycine (DMG).
Dimethylglycine is a naturally occurring carboxylic acid that is often used as a dietary supplement to improve physical performance. DMG has also been shown to have positive effects on key parameters of skin biology, including promoting cell growth and supporting synthesis and release of growth factors such as VEGF.
Further clinical data demonstrate positive effects on skin parameters, if DMG is topically applied: an improvement in skin microcirculation was demonstrated after the usage of a gel containing DMG compared to a placebo formulation without any active ingredient.
Studies indicate synergies of caffeine and DMG
After the synergistic effect of caffeine and DMG had already been presented to researchers at previous congresses in Melbourne and Rome, Dr. Erik Schulze zur Wiesche presented two randomized, placebo-controlled, double-blinded studies at the EHRS meeting, which were carried out on a total of 308 male subjects (aged 18 to 65 years) with androgenetic alopecia: The subjects used either a tonic or shampoo containing caffeine and DMG or a corresponding placebo.
In both studies, hair loss rates, measured by a standardized hair picking test, were significantly lower when using the verum compared to placebo. Also noteworthy: a phototrichogram analysis of a subgroup on a smaller area on the head showed an increased hair number and hair density after six months of application of the caffeine and DMG-containing tonic or shampoo.
“These results underline the great potential of caffeine and DMG as a new treatment against male pattern hair loss,” summarized Dr. Schulze zur Wiesche.
New drug “Axhidrox®” against pathological sweating in the armpits available in Germany as of August
New studies in caries- & hairloss research
Also, in the second Corona year Bielefeld-based Dr. Wolff Group accomplished stable growth. Strong brands, innovative products, ongoing internationalisation, and further digitalisation formed the foundation in turbulent times. As in the previous year, the focus in 2021 was on the following topics: employee health, supply chain, cash management as well as research and development of new products. Thus, in 2021, Bielefeld-based Dr. Wolff Group recorded the highest turnover to date in the company’s 117-year history at 357.2 million euros (2020: 341.1 million euros), achieved a plus of almost five percent and increased turnover despite Corona in the past two years.
Expansion of international locations
Exports also continued to grow worldwide despite Corona. Finland was added as a new international location, while the teams in the USA, in Singapore and in China were further expanded. In total, the company now globally operates 12 locations for marketing and sales in the regions. “We are focusing on further very dynamic growth. To achieve this, we will continue to expand our markets, consistently defy possible crisis scenarios in the coming years and actively invest in research and in our brands,” says Eduard R. Dörrenberg, Managing Partner of Dr. Wolff Group.
Potentials of innovative products and progressive digitalisation
Due to the outbreak of war in Europe, the consequences of emerging inflation, increasing cost pressure and a still unstable Corona situation, the challenges have grown significantly. Nevertheless: “We will remain optimistic for the long term, and we will continue to globalise our successful and evidence-based products, and further expand our team, too, which today consists of 785 employees. Furthermore, we have made great progress with our digitalisation strategy, which we started back in 2014, and will continue to expand it,” Dörrenberg stated at the annual balance press conference. In general, the company is focusing on research for new innovative products. At the top of the agenda are continuing internationalisation in the cosmetics sector, and expansion in the oral care division. In the pharmaceuticals sector Dr. Wolff Group has opened another business area with the EU-wide launch of the new “Axhidrox®” drug.
Product from Bielefeld supports virus prophylaxis
From the beginning of the pandemic on Dr. Wolff’s maxim has been to complement existing Corona protection measures in the best possible way, and to make an effective contribution. In 2021, the oral care segment developed a concept to support virus prophylaxis based on an antiviral mouth and throat rinse. Most recently, a group of 13 scientists1 confirmed its effectiveness in reducing the SARS-CoV-2 viral load in the mouth and throat area. A special mention was made of the surfactant-based efficacy concept used by Dr. Wolff, while in particular antiseptic agents showed hardly any effects. “We do not replace any vaccination or any of the established hygiene measures. We complement them. It is remarkable that especially consumer protection centres publicly doubt the work of respected scientists and university clinics and sometimes even fight it legally,” describes the 54-year-old managing partner the current discussion about the antiviral mouth and throat rinse.
Research success and new therapy option: drug against excessive sweating
After about ten years of research and development, Dr. Wolff launched a new drug against excessive sweating in the armpits in 2022. Following approval, the drug named “Axhidrox®” is already available in Austria. The launch in Germany is scheduled for August. In Germany, at least four million people suffer from so-called primary hyperhidrosis, a chronic disease with a high number of unreported cases. Those affected sweat excessively without any recognisable cause. With the development of the cream containing 1% glycopyrronium bromide (GPB), the dermatology division at Dr. August Wolff has succeeded in providing patients with so-called severe primary axillary hyperhidrosis with a new treatment option.
“Our preparation is the only anticholinergic cream in Europe to date that allows for the external treatment of severe primary axillary hyperhidrosis with the active ingredient GPB. We are convinced that with this drug we can also help patients who have not achieved satisfactory results with previous treatment options so far,” says the family businessman. Data from several clinical trials provided the basis for the approval in eleven European countries. The data of the phase 3a trial relevant for approval were already published in 2021 in the highly respected “British Journal of Dermatology”.2 The publication of the phase 3b research data is expected shortly. In Germany, the preparation will be presented to dermatologists for the first time in mid-July at a scientific congress. Dr. Wolff will gradually put the preparation on the market in the eleven EU countries directly or via partners.
Forecast
“Hardly anyone could or wanted to imagine that the pandemic would be immediately followed by another crisis. We know that we need to adjust to a ‘life with crisis’ and therefore remain very flexible,” says Dörrenberg with regard to the current circumstances. Overall, the situation in the entire supply chain is tense. For Dr. Wolff as a manufacturer of high-performance products the challenges are increasing, too, but so are the opportunities. The management consultancy McKinsey, e.g., recently provided data3 on consumer attitudes and buying behaviour that confirmed the importance of developing innovative products with real benefits. In addition, further internationalisation is to ensure independence for the Bielefeld-based company. On this path, Bielefeld-based Dr. Wolff Group is planning on further growth in the current financial year. With the launch of the “Axhidrox®” drug against heavy sweating in the armpits, we want to add company locations throughout Europe and also bring this drug to Asia as quickly as possible,” Dörrenberg states. The shampoo manufacturer also takes advantage of the start of this year’s Tour de France in Denmark and the attention given to their own professional cycling team to actively enter the Danish market with Alpecin, and from there the entire Scandinavian market. In addition to strong brands and products with a great performance promise, Dr. Wolff continues to focus on digitalisation. The eWolff business unit currently employs more than 30 digital specialists and is expected to have grown to 50 employees by the end of the year. The office space of this unit got doubled within the Dr. Wolff headquarters and the internal exchange on digital topics has been significantly increased. “Overall, we are very well prepared to tackle the upcoming challenges as well as the upcoming opportunities,” says Dörrenberg.
Business areas in detail
Pharmaceutical sector
Dermatology:
One-off effects of the pandemic that occurred in 2020 and early 2021, especially due to the intensive corona-related use of hand disinfection as well as antiviral mouth and throat rinses, were not repeated due to the easing of measures in 2021. With a total of 57.5 million euros, turnover was nevertheless around 7 million above the “pre-Corona result”. In 2019, dermatics sales amounted to about 50 million euros.
Gynaecology:
There have never been more women in Germany going through menopause. Changing demographics also lead to changing communication. “We see a new openness to address things,” Dörrenberg says and identifies further potential in this division. Dr. Wolff’s gynaecological products have been making a major contribution for years, e.g., in hormone-free therapy, which is particularly important according to the guidelines of many international markets. In the past year, the Vagisan brand again grew by 4 percent in Germany and abroad. Sales amounted to 38.6 million euros. Apposite to the new openness, sexologist Ann-Marlene Henning, who openly addresses difficult issues such as vaginal dryness, continues to be the brand ambassador.
Cosmetics
Oral Care:
With sales of over 33 million euros, Dr. Wolff’s fluoride-free products in the oral care category (+16 percent) are growing many times more dynamically than the market. According to the German Cosmetic, Toiletry, Perfumery and Detergent Association (Industrieverband Körperpflege- und Waschmittel – IKW), the entire oral care sector is stagnating at around 1.6 percent. Dörrenberg also sees great future potential in the oral care segment. The company is expanding international activities with their Bioniq® brand. In addition, the Karex brand is extremely successful with children’s toothpaste and almost doubled in sales. In June 2022, the new Junior Karex toothpaste was added to the portfolio. As a consequence, investments in infrastructure and organisational structures at the Bielefeld company headquarters were made. In the oral care area, research with far-reaching studies on modern caries prophylaxis and education about European regulations on the dosage of fluoride-containing toothpaste is a focal point. For years, international scientists have been actively working on the evidence of the active ingredient complex around the ingredient hydroxyapatite. The Canadian organisation Health Canada officially listed Kinder Karex in 2022 and recommends the fluoride-free toothpaste from Germany to all Canadian dentists. In the past ten years, more intensive research on hydroxyapatite and its positive influence on dental health has been conducted worldwide than on any other oral care ingredient. Numerous studies and publications show that hydroxyapatite is a real alternative to fluoride4.
Plantur:
Due to strong one-off effects caused by the lockdown measures, especially in the field of colour effect products, the Plantur range grew again by 19 percent in the previous year. With total sales of almost 85.5 million euros, the products of the female caffeine shampoo range almost reached the level of the men’s brand Alpecin. For many women as well as men, the decisive purchase criterion still is being able to actively do something about hair loss. Caffeine is the means of choice. The Bielefeld scientists have repeatedly been acknowledged by international experts, e.g., by the conclusion of a British research group led by Dr. Gil Westgate (University of Bradford), whose publication confirms that caffeine is the best-researched active ingredient of plant origin against hair loss.
Alpecin:
About one in two men is affected by hair loss in the course of his life. The cause of hair loss is hereditary in 80 percent of cases. Alpecin Caffeine Shampoo stands for slowing down the process and providing effective prevention. Education and awareness, especially of young men, is important for the Bielefeld-based company. According to IKW, the entire market for hair care products lost 2.4 percent in 2021. Alpecin, however, is a driver in this segment. The brand grew by over 5 percent in Germany. Internationally, the caffeine shampoo from Bielefeld even gained 27 percent. The cumulative turnover thus amounts to 93.4 million euros.
Alcina:
With all in all two lockdowns, the hairdressing business was compromised by the pandemic until 2021. Alcina managed to respond to this due to company-wide digital activities. The new “diversity” collection and all corresponding seminar and workshop series were presented digitally, and the content was deepened in weekly online presentations. Nevertheless, personal engagement and advice in the B2B segment came up short. With sales of 37 million euros, Alcina did not reach the “pre-Corona level” with hair-, skin care- and decorative cosmetics. For the current year, the goal is to revive business with seasonal editions and especially with hair colours.
1Meister T. L. et al. Mouthrinses against SARS-CoV-2 – High antiviral effectivity by membrane disruption in vitro translates to mild effects in a randomized placebo-controlled clinical trial”. Elsevier, 2022 July. https://doi.org/10.1016/j.virusres.2022.198791
2Abels C, Soeberdt M, Kilic A, Reich H, Knie U, Jourdan C, Schramm K, Heimstaedt-Muskett S, Masur C, Szeimies RM. A 1% glycopyrronium bromide cream for the topical treatment of primary axillary hyperhidrosis: Efficacy and Safety Results from a Phase 3a Randomised Controlled Study. Br J Dermatol. 2021 Jan 14. doi: 10.1111/bjd.19810
3McKinsey & Company Europe Consumer Pulse Survey, 4/12-4/18/2022 n= 5.075 (France, Germany, Italy, Spain, UK) sampled to match European general population 18+ years
4among others: Meta-Analyse Limeback et al.2021: Limeback, H., Enax, J. & Meyer, F. Biomimetic hydroxyapatite and caries prevention: a systematic review and meta-analysis. Can J Dent Hyg 55, 148-159 (2021); v55n3.pdf (cdha.ca)
First anticholinergic cream against heavy underarm sweating currently approved in 11 European countries
In the future, a new therapy option will be available for patients with severe primary axillary hyperhidrosis in various European countries: After the Swedish reference authority recommended the approval of the topical medication for severe sweating in the armpits, the feedback from the individual countries is now being received.
Eleven countries have so far granted marketing authorisation for the topical cream containing 1% glycopyrronium bromide (brand name Axhidrox). The gradual market launch of the product in the respective countries is in preparation.
Glycopyrronium bromide (INN name, abbreviation GPB) or glycopyrrolate (USAN name) is a well-known anticholinergic drug substance approved in several products marketed in the EU and the USA for various diseases in children and adults. GPB blocks the action of acetylcholine at muscarinic acetylcholine receptors, which are responsible for sweat gland activation, among other things.
About hyperhidrosis
Approximately 5 % of people worldwide suffer from permanent excessive sweating without an identifiable cause, so-called “primary hyperhidrosis”. This chronic disease is a great burden for patients and severely limits their quality of life. Primary hyperhidrosis ranges in severity from mild wetness to heavy dripping and can lead to a significant impact on quality of life. This may significantly affect work, social relationships, physical and leisure activities, as well as emotional and mental health. Patients with primary axillary hyperhidrosis suffer from excessive sweat production in the armpits beyond the amount required to regulate normal body temperature.
About Dr. Wolff
Dr. Wolff – since 1905, the name has stood for research that solves people’s skin-, hair-, and dental problems with innovative active ingredients. We focus our effort on scientifically proven benefits of the products. Since the company was founded, Dr. Wolff has maintained close cooperation with renowned scientists. From the first branded product, Hämatopan, to today’s internationally available products, in-house research provides the basis for innovative active ingredients and product developments. The company is managed by the fourth generation of the family and is growing with 780 employees worldwide. Dr. Wolff operates in 62 countries. For more information, please go to: Dr. Wolff Group
Dr. August Wolff and Cantabria Labs enter into an exclusive commercialization agreement for Southern Europe for hyperhidrosis product
Promising German-Spanish partnership between Dr. August Wolff and Cantabria Labs officially sealed
Cantabria Labs acquired the exclusive right to commercialize an oil-in-water cream containing 1 % glycopyrronium bromide (GPB) in Spain, Italy and Portugal
Unique cream formulation is indicated for primary axillary hyperhidrosis and is currently nearing completion of a pivotal (phase 3b) trial in Europe.
Bielefeld/Madrid: The German pharmaceutical company Dr. August Wolff GmbH & Co. KG Arzneimittel (“Dr. Wolff”) and the Spanish pharmaceutical company Cantabria Labs (“Cantabria Labs”) concluded a strategic partnership on March 12th 2021 by entering into an exclusive licensing agreement for a newly developed medicinal product for the treatment of hyperhidrosis. Under the terms of the license agreement, Cantabria Labs will have the exclusive right to commercialize an oil-in-water cream with 1 % glycopyrronium bromide (GPB) in Spain, Italy and Portugal. In return, Dr. Wolff Group will receive upfront, milestone as well as royalty payments and will additionally be the exclusive supplier for the finished product.
“March 12th 2021 was a historic day for both companies and paves the way for a promising partnership. With Cantabria Labs’ strength in the Dermatologic Field as well as the reach of their distribution channels in Southern Europe, we couldn’t be more pleased to have Cantabria Labs as our first partner for GPB cream. Once approved, the cream will be the first topical GPB treatment for primary axillary hyperhidrosis in Europe. Given that many hyperhidrosis patients do not achieve satisfactory results with existing treatments, we believe that our product might contribute significantly to improve the outcomes for patients suffering from this disease”, said Eduard R. Dörrenberg, one of Dr Wolff’s Managing Partners.
“This deal represents the beginning of what will be a long, rewarding partnership between our two companies based on common commitment to innovation, entrepreneurship and caring. It allows our laboratories to introduce an innovative new product into a market offering few effective alternatives. GPB cream will further strengthen our position in dermatology built up over the years through close collaboration with physicians. These physicians will undoubtedly appreciate the innovation and continue to provide support for our product development”, commented Susana Rodríguez, Cantabria Labs CEO.
Despite the challenges of the COVID-19 pandemic, Dr. Wolff was able to file the Marketing Authorisation Application (MAA) – the submission of the 1st DCP in the European Union regarding GPB cream took place on Feb 26th. If approved, the Marketing Authorisation (MA) would apply to Germany and 10 other European countries. Cantabria Labs will follow with an independent Southern European DCP covering Italy, Portugal and Spain. Further Marketing Authorization Applications in additional global markets will follow. Dr. August Wolff intends to commercialize the GPB Cream directly or with experienced partners globally.
The drug is currently in the long-term open-label extension of the clinical trial (phase 3b), which will be completed beginning of Q4 2021. Positive results of the Phase 3a part of the pivotal Phase 3 study in patients with primary axillary hyperhidrosis were recently published in British Journal of Dermatology[i].
About Cantabria Labs
With its innovative products and entrepreneurial spirit, today Cantabria Labs is a leading brand in dermatological prescription in Europe (leader in Spain, Italy and Portugal) with the aim of improving people’s health and quality of life. Its presence in over 80 countries and subsidiaries in France, China, Italy, Morocco, Mexico and Portugal have earned it an excellent international reputation and support. Cantabria Lab’s production centres work in accordance with the highest quality standards for manufacturing and distributing its over 30 million product units yearly. Cantabria Labs has an entrepreneurial, nonconformist and joyful spirit, and aims to offer people products that allow them to enjoy an excellent quality of life: celebrate life. Cantabria Labs
About Dr Wolff
Ever since its establishment in 1905, Dr. Wolff, together with leading scientist in the field, develops products that solve the skin, hair and dental problems. The focus of the company are products with scientifically proven benefits. From the first branded product Haematopan to the products available internationally today, Dr. Wolff´s innovative product development provides the basis for new active ingredients and product developments.
The company is now in its fourth generation of family-run management and is on a worldwide growth course with 780 employees. Dr. Wolff operates in 62 countries. For further information please visit Dr. Wolff Group.
About Glycopyrronium bromide
Glycopyrronium bromide (INN name, abbreviation GPB) or glycopyrrolate (USAN name) is a well-known anticholinergic acting drug substance approved in several marketed products in the EU and the USA for various diseases of children and adults. GPB blocks the action of acetylcholine at cholinergic receptors responsible among others for sweat gland activation.
About Hyperhidrosis
Approximately 5% people worldwide suffer from permanent excessive sweating, so-called “primary hyperhidrosis” which is a great burden for the patients and has severe impact on the quality of life. Yet, more than 50% of all hyperhidrosis patients receive no treatment. Patients with primary axillary hyperhidrosis suffer from an excessive amount of sweat production in the armpits beyond what is needed in order to regulate normal body temperature. Primary hyperhidrosis can range in severity from mild dampness to severe dripping and can result in substantial impairment in quality of life. This may significantly affect work, social and romantic relationships, physical and leisure activities as well as emotional and mental health.
Detailed study results of the phase 3a part
The Phase 3a part of this pivotal Phase 3 study, conducted in Germany, Hungary, Poland, Sweden, Denmark and UK, evaluated a total of 171 subjects randomized 1:1 to apply 1% GPB (n=84) or vehicle cream (placebo, n=87) to the axillae for 28 days. All subjects had Hyperhidrosis Disease Severity Scale (HDSS) scores ≥ 3 and ≥ 50 mg/5 min gravimetric sweat production in each axilla at baseline. Overall favourable results for 1% GPB Cream over Placebo were shown as follows:
Mean sweat production was reduced by 197.08 mg for the 1% GPB cream and 83.49 mg for placebo. Absolute reduction in sweat production from Baseline to Day 29 in logarithmic values was statistically larger in the 1% GPB cream compared to placebo (p = 0.0038; mixed effects model). Hence, the primary endpoint of the study was met. HDSS showed a change from baseline clearly favoring 1% GPB treatment over placebo at day 15 (difference in median: -1.0; p = 0.0020) and day 29 (p = 0.0138). Response to treatment based on the HDSS (an improvement of 2 points or more), a key secondary endpoint (for day 29) nearly reached statistical significance (p = 0.0542).
Ongoing Phase 3b part is investigating the long-term safety and efficacy of 1% GPB cream up to 72 weeks. Enrollment of the Phase 3b part has been completed. In total, 517 patients have been enrolled. For the MAA dossier, long-term safety data over 6 months are available for 315 patients, and 12-month data are available for 100 patients. The study is continuing treatment for 72 weeks, to collect further long-term safety data.
[i] Abels C, Soeberdt M, Kilic A, Reich H, Knie U, Jourdan C, Schramm K, Heimstaedt-Muskett S, Masur C, Szeimies RM. A 1% glycopyrronium bromide cream for the topical treatment of primary axillary hyperhidrosis: Efficacy and Safety Results from a Phase 3a Randomised Controlled Study. Br J Dermatol. 2021 Jan 14. doi: 10.1111/bjd.19810.
Dr. August Wolff Submits Application for Marketing Authorization of 1% Glycopyrronium Bromide (GPB) Cream in the EU – Positive Phase 3a Part of Pivotal Study Results for 1% GPB Cream in Patients with Primary Axillary Hyperhidrosis
Filing of the documents for marketing authorisation application (MAA) in a decentralised procedure (DCP) on February 26th, 2021
Primary endpoint (absolute change in sweat production) was met with statistical significance
Key seconday endpoints showed about 2 times as many responders to 1% GPB treatment than to placebo
The Bielefeld-based family-owned pharmaceutical developing and manufacturing company Dr. August Wolff GmbH & Co. KG Arzneimittel (“Dr. August Wolff”) announces that the “Marketing Authorisation Application” (MAA) for 1% Glycopyrronium bromide (GPB) cream was submitted on February 26th to the Medical Products Agency (MPA, Sweden) despite the challenges of the COVID-19 pandemic. If approved, the MAA would apply to Austria, Croatia, Denmark, Estonia, Finland, Germany, Latvia, Lithuania, The Netherlands, Norway and Sweden. Dr. August Wolff will commercialize the GPB Cream directly or with experienced partners in these countries.
The application package for 1% GPB cream includes i.a. data from a combined Phase 3a/Phase 3b study in patients with primary axillary hyperhidrosis. The long-term part of the study will be completed beginning of Q4 2021. Positive results of the Phase 3a part of the pivotal Phase 3 study in patients with primary axillary hyperhidrosis were recently published in British Journal of Dermatology[1]. The primary endpoint (absolute change in sweat production assessed by gravimetric measurement from Baseline (Day 1) to Day 29 in the 1% GPB group compared with the placebo group was met with statistical significance. In addition, hyperhidrosis-related quality of life improved significantly.
“We are extremely encouraged by these positive results which together with results from planned interim analyses of the Phase 3b part are used for the filing of the marketing authorization application in EU” said Eduard R. Dörrenberg, one of the Dr Wolff´s Managing Partners. “Once approved, the cream will be the first topical GPB treatment for primary axillary hyperhidrosis in Europe. Given that many hyperhidrosis patients do not achieve satisfactory results with existing treatments, we believe that our product might contribute significantly to improve the outcomes for patients suffering from this disease.”
Detailed study results of the phase 3a part
The Phase 3a part of this pivotal Phase 3 study, conducted in Germany, Hungary, Poland, Sweden, Denmark and UK, evaluated a total of 171 subjects randomized 1:1 to apply 1% GPB (n=84) or vehicle cream (placebo, n=87) to the axillae for 28 days. All subjects had Hyperhidrosis Disease Severity Scale (HDSS) scores ≥ 3 and ≥ 50 mg/5 min gravimetric sweat production in each axilla at baseline. Overall favourable results for 1% GPB Cream over Placebo were shown as follows:
Mean sweat production was reduced by 197.08 mg for the 1% GPB cream and 83.49 mg for placebo. Absolute reduction in sweat production from Baseline to Day 29 in logarithmic values was statistically larger in the 1% GPB cream compared to placebo (p = 0.0038; mixed effects model). Hence, the primary endpoint of the study was met. HDSS showed a change from baseline clearly favoring 1% GPB treatment over placebo at day 15 (difference in median: -1.0; p = 0.0020) and day 29 (p = 0.0138). Response to treatment based on the HDSS (an improvement of 2 points or more), a key secondary endpoint (for day 29) nearly reached statistical significance (p = 0.0542).
Ongoing Phase 3b part is investigating the long-term safety and efficacy of 1% GPB cream up to 72 weeks. Enrollment of the Phase 3b part has been completed. In total, 517 patients have been enrolled. For the MAA dossier, long-term safety data over 6 months are available for 315 patients, and 12-month data are available for 100 patients. The study is continuing treatment for 72 weeks, to collect further long-term safety data.
About Glycopyrronium bromide
Glycopyrronium bromide (INN name, abbreviation GPB) or glycopyrrolate (USAN name) is a well-known anticholinergic acting drug substance approved in several marketed products in the EU and the USA for various diseases of children and adults. GPB blocks the action of acetylcholine at cholinergic receptors responsible among others for sweat gland activation.
About Hyperhidrosis
Approximately 5% people worldwide suffer from permanent excessive sweating, so-called “primary hyperhidrosis” which is a great burden for the patients and has severe impact on the quality of life. Yet, more than 50% of all hyperhidrosis patients receive no treatment. Patients with primary axillary hyperhidrosis suffer from an excessive amount of sweat production in the armpits beyond what is needed in order to regulate normal body temperature. Primary hyperhidrosis can range in severity from mild dampness to severe dripping and can result in substantial impairment in quality of life. This may significantly affect work, social and romantic relationships, physical and leisure activities as well as emotional and mental health.
About Dr Wolff
Ever since its establishment in 1905, Dr. Wolff, together with leading scientist in the field, develops products that solve the skin, hair and dental problems. The focus of the company are products with scientifically proven benefits. From the first branded product Haematopan to the products available internationally today, Dr. Wolff´s innovative product development provides the basis for new active ingredients and product developments. The company is now in its fourth generation of family-run management and is on a worldwide growth course with 780 employees. Dr. Wolff operates in 62 countries. For further information please visit Dr. Wolff Group.
[1] Abels C, Soeberdt M, Kilic A, Reich H, Knie U, Jourdan C, Schramm K, Heimstaedt-Muskett S, Masur C, Szeimies RM. A 1% glycopyrronium bromide cream for the topical treatment of primary axillary hyperhidrosis: Efficacy and Safety Results from a Phase 3a Randomised Controlled Study. Br J Dermatol. 2021 Jan 14. doi: 10.1111/bjd.19810.
