Cosmo’s therapeutic focus is on the treatment and/or prevention of gastrointestinal diseases (including IBD, colonic infections and colorectal cancer – CRC), on increasing the effectiveness of endoscopic examinations and to treat persistent skin conditions, like acne, that have a long-term physical and emotional impact on lives and self-esteem.
The blend of our knowledge of the colon and the unique characteristics of the MMX® technology gives us a strong competitive edge in developing new applications for the colon without having to primarily resort to the expensive and risky pure research process for new chemical entities.
Inflammatory bowel diseases (IBD)
Inflammatory Bowel Diseases (IBD) are a group of chronic, progressive, recurring and debilitating disorders characterized by severe damage of the gastro-intestinal tract. The main forms of IBD are Ulcerative Colitis and Crohn’s Disease. These diseases are clinically similar and may be described as a faulty regulation of the immune response in the gut.
The causes of the Inflammatory Bowel Diseases are not known, but it is widely believed that they could be ascribed to a combination of environmental, immune, and bacterial factors in genetically susceptible individuals. Diet is also believed to play an important role in the pathogenesis, and high-fat or high-protein diets are believed to be risk factors for these diseases.
Inflammatory Bowel Diseases currently affects approximately 11.2%[1] of the world’s population. According to the U.S. Crohn’s and Colitis Foundation, the Ulcerative Colitis and Crohn’s Disease U.S. population size is estimated to be in excess of 3[2] million patients.
In terms of severity, both Crohn’s disease and UC patients are generally categorized in three different categories (mild, moderate and severe); the therapeutic approach depends on the extent and severity of the disease.
Cosmo is addressing these needs with commercial products (e.g., Lialda®, Uceris®) in certain regions.
Colonic infections
Colon infections are a group of diseases which range from short infections such as travelers’ diarrhea and to hepatic encephalopathy (HE), clostridium difficile infection and acute diverticulitis.
Travelers’ diarrhea (TD) primarily strikes people traveling to developing countries after ingesting food or drinks that are contaminated by bacteria. It is estimated that at least 46 million US people travel to every year to countries at medium or high risk of TD and that around 40% of these will get TD[3].
HE is caused by cirrhosis of the liver when the liver can no longer perform all its bacteria cleaning functions. The toxins can then travel to the brain and cause severe brain damage.
Diverticulosis happens when pouches (diverticula) form in the walls of the colon. It is presumed that about 60% of the 60-year-old have diverticula, 70% of the 70 years old etc. It is also presumed that the peristaltic muscle structure becomes more brittle as persons age and that pressure from within the colon then causes the pouches to form. If these pouches get inflamed or infected, it is called acute diverticulitis. This happens in approximately 10-20% of all cases. Diverticulitis can be very painful.
Cosmo is addressing these needs with commercial products (e.g., Aemcolo®) in certain regions.
Colorectal cancer (CRC)
CRC is the third leading cause of cancer-related deaths in men and women. Epidemiologists estimate that, at birth, every person has a 4.49% (men) 4.15% (women)[4] chance of contracting CRC during its lifetime with the disease primarily striking people that are older than 45 years.
Survival rates vary significantly depending on the stage at which CRC is diagnosed; the 5-year survival rate is 65%[5] in the USA and 56%[6] in Europe. However, since practically all CRC develop from adenomas, CRC is the only cancer that theoretically could be eradicated by developing means of detecting the adenomas as early as possible and by extracting them without major surgery.
In Europe it is a standard procedure in many countries that each subject, upon its 50th birthday, is screened for CRC with a prescreening test, for instance the FOBT test. If this test proves positive, the subject is then referred to a colonoscopy. In the USA, the use of FOBT tests is less frequent with subjects in the great majority opting for a direct colonoscopy.
The increased frequency of preventive measures has had a strong impact on CRC incidence. In 2000 it was estimated that by 2015 approximately 200’000 subjects would be diagnosed with colon cancer. The most recent estimates made by the US authorities now project cancer diagnoses to be down to 101’420[7] cases annually, a substantial decrease largely due to increased number of colonoscopies. In Europe it is estimated that 447’000 people are diagnosed with CRC in 2016.
In order to identify polyps, endoscopists perform colonoscopies which allow a visual inspection of the colon via endoscope. During colonoscopy, endoscopists strive to identify all polyps and remove those potentially dangerous. Removal of polyps can be challenging, especially if the polyp is flat or positioned in difficult areas.
In clinical practice, adenoma detection rate (‘ADR’) is the percentage of patients undergoing a first-time screening colonoscopy who have one or more conventional adenomas detected and removed. ADR is a key quality indicator for colonoscopy; a high ADR is associated with a low post colonoscopy CRC, therefore increasing ADR is key to reducing the incidence of CRC.
Cosmo is addressing these needs with commercial products (e.g., Methylene Blue MMX®, Eleview® and GI Genius™) in certain regions.
Acne
Acne is the eighth most prevalent disease in the world, affecting more than 640 million people. Although acne often coincides with puberty affecting c. 85% of adolescents, it also impacts young adults (aged 12–25 years) and may persist into, or develop during, adulthood.
Acne is a multifactorial inflammatory condition characterised by excess skin oil (sebum) production, a build-up of dead skin cells that clog the pores and growth of bacteria that further enhance inflammation, redness and pore blockage. These events lead to acne’s characteristic lesions.
Treatment of acne usually involves combinations of oral and/or topical treatments. Antibiotic resistance in acne is a concern.
Androgen hormones are a key driver of acne in both males and females with acne. Androgen receptors (‘ARs’) are expressed throughout the skin and found in the sebum producing glands. Circulating and locally (skin)-synthesized androgens such as testosterone and dihydrotestosterone (‘DHT’) bind to the AR and stimulate sebum production in both males and females. Androgen inhibition is an effective strategy for the treatment of female acne. Certain COCs (norgestimate, norethindrone) are FDA-approved to treat acne in females; these drugs suppress androgen production, thereby reducing circulating androgens.
Cosmo is addressing these needs with commercial products (e.g., Winlevi® (clascoterone cream 1%)) in certain regions.
Androgenetic Alopecia (AGA)
Androgen induced alopecia, also known as Androgenetic Alopecia or patterned hair loss, is the most common type of hair loss affecting an estimated 50 million men and an estimated 30 million women in the U.S.
Of these, only 25-30 million men and 15-20 million women have been diagnosed, and only 2.7 million men and 2 million women or 5-10% of the total are actually being treated. A vast majority of patients have not sought treatment for their condition, likely due to the limitations of current treatments and the lack of available options. In AGA, high local concentrations of DHT bind to androgen receptors within the scalp hair follicles, resulting in shortening of the hair cycle and gradual miniaturisation of scalp follicles in men and women with a genetic predisposition. Over time, these progressively smaller, thinner hair follicles are unable to produce new hair, thus resulting in AGA’s characteristic patterned baldness. DHT-dependent effects are considered, in most cases, reversible, yet a topical treatment that can be used in both males and females with AGA remains elusive.
Cosmo is addressing these needs by developing an investigational product (clascoterone 5% solution, tradename: Breezula® (Clascoterone solution)) in certain regions.
[1] Hewings-Martin, Yella. “IBS: Five facts you need to know”. www.medicalnewstoday.com. MedicalNewsToday, November 29, 2017. Web. November 21, 2019.
[2] National Center for Chronic Disease Prevention and Health Promotion, Centers for Disease Control and Prevention. “Inflammatory Bowel Disease Prevalence (IBD) in the United States”. www.cdc.gov. March 21, 2019. Web. November 21, 2019.
[3] Connor, Bradley A. “Travelers’ Diarrhea”, Yellow book. www.cdc.gov. June 24, 2019. Web. November 21, 2019.
[4] The American Cancer Society medical and editorial content team. “Key Statistics for Colorectal Cancer”. www.cancer.org. February 21, 2018. Web. November 21, 2019.
[5] Cancer.Net Editorial Board. “Colorectal Cancer: Statistics”. www.cancer.net. November, 2018. Web. November 21, 2019.
[6] Cancer Research UK. “Bowel cancer survival statistics”. www.cancerresearchuk.org. February 6, 2017. Web. November 21, 2019.
[7] Finlay A Macrae. “Colorectal cancer: Epidemiology, risk factors, and protective factors”. www.uptodate.com. September 20, 2019. Web. November 21, 2019.