Innovation Pharmaceuticals Inc.
July 9, 2017
Ulcerative Proctitis / Ulcerative Proctosigmoiditis — Opportunity for Newer Therapies Like Brilacidin to Emerge
Brilacidin
Ulcerative Proctitis/Ulcerative Proctosigmoiditis
Ulcerative Proctitis and Ulcerative Proctosigmoiditis (UP/UPS) are two mild forms of Ulcerative Colitis (UC), an Inflammatory Bowel Disease (pdf) (IBD), involving only the rectum and distal colon.
UP/UPS can be characterized by inflammation, redness, and ulcerations of the mucosal lining. Symptoms include frequent stools and diarrhea (with or without blood), as well as abdominal urgency, such as cramping and constipation. The clinical course of the disease is highly variable, ranging from complete resolution, to maintained remission, to chronic relapses and refractory disease. Progression of UP/UPS into more extensive disease, to full UC, occurs in up to 50 percent of patients.
The cause of UP/UPS is undetermined, though evidence suggests complex interactions between the environment, the intestinal microbiome, immune dysregulation, and a genetic predisposition, may be contributing factors. Diagnosis can occur at any point in one’s life and there currently is no cure.
According to estimates provided by GlobalData, the Worldwide UC market, which includes UP/UPS, is expected to increase at a compound annual growth rate of 4.7 percent, from $4.2 billion in 2012 to approximately $6.6 billion by 2022. The larger anti-inflammatory market, comprising IBD, arthritis, respiratory disease, multiple sclerosis, psoriasis, and other inflammatory diseases, is expected to reach $106.1 billion by 2020.
Current UP/UPS Treatment Options
IBD therapy generally focuses on anti-inflammatory immunosuppression based on the severity and location of the disease. Rectally-applied treatments can be particularly effective in treating distal colitis -- e.g., suppositories for UP or enema/foam preparations for UPS. Common medications for the treatment of UP/UPS include steroids and 5-aminosalicyclic acid (5-ASA), a $1.4 billion market.
Topical steroids may be administered to patients who fail or do not tolerate 5-ASA therapy. Oral corticosteroids may also be given to patients, though their extended use can be associated with serious side-effects. Rectally-applied steroids offer advantages compared to oral drugs, providing targeted treatment (localized concentration of medication) to areas of active inflammation with less risk of adverse systemic effects.
Budesonide (marketed under the brand name Uceris) is a second-generation corticosteroid used either topically or orally in patients with more limited forms of UC. Both enema and foam formulations are available to treat patients. A six-week course of budesonide foam is recommended to help induce remission, with twice-daily dosing for the first 2 weeks, followed by once-a-day dosing for the remaining 4 weeks. The cost of budesonide foam, around $1,280 for a six-week course, makes it an attractive treatment option compared to more expensive biologic therapies, typically reserved for severe cases of UC. Uceris's patent is set to expire in 2020.
Budesonide was approved by the Food and Drug Administration (FDA) in October 2014 based on two successful Phase 3 trials (published findings) -- 38.3 percent and 44 percent of patients on budesonide foam achieved remission at 6 weeks compared to 25.8 percent and 22.4 percent on placebo. Combined results showed a remission rate of 41.2 percent with budesonide foam and 24 percent with placebo.
In March 2017, Salix Pharmaceuticals, acquired by Valeant Pharmaceuticals for $14.5 billion in 2015, published results showing extended release tablets of budesonide achieved both clinical and endoscopic remission, touting its ability to deliver "complete UC relief" in mild-to-moderate cases, and emphasizing the use of, in its clinical trials, "the stringent endpoint of endoscopic remission." In two trials, 17.9 percent and 17.4 percent of patients taking Uceris tablets achieved remission compared to 7.4 percent and 4.5 percent, respectively, on placebo.
Brilacidin as a Promising, Non-Corticosteriod, Non-Biologic Treatment for IBD
With its unique immunomodulatory profile as a defensin-mimetic -- defensins play a special role in the regulation of mucosa and the intestinal barrier -- Brilacidin is being developed as a promising, novel, non-corticosteroid, non-biologic treatment for IBD.
Innovation Pharmaceuticals completed treatments in the final cohort in its Phase 2 Proof-of-Concept (PoC) clinical trial in UP/UPS and will be presenting topline results at the Drug Discovery & Therapy World Congress in Boston, MA, on July 13, 2017.
Formulation development plans for Brilacidin in IBD include foam and/or gel for the treatment of UP/UPS, as well as tablets for oral dosing in UC and Crohn’s Disease. Newer formulations may result in added retention and a more uniform distribution of Brilacidin, potentially increasing efficacy, while being more amenable to patients.
