Recently, clinical stage biopharmaceutical company Immunic, Inc. (“Immunic”) has been working to develop potential treatment options for patients with primary sclerosing cholangitis (PSC), a rare condition for which no current treatments exist. In a press release, Immunic shared positive data from a Phase 2 proof-of-concept study evaluating the company’s drug candidate IMU-838 for PSC. Although only 11 patients fulfilled the entire treatment course over a 24-week (5.5 month) period, researchers believe that the treatment shows promise moving forward.
IMU-838
During the Phase 2 clinical trial, researchers evaluated IMU-838, an orally administered dihydroorotate dehydrogenase (DHODH) inhibitor and immune modulator. When DHODH is blocked, activated T and B cells, which play a role in immune function, are also inhibited. Many consider PSC to be somewhat of an autoimmune condition. However, IMU-838 only blocks certain cells, allowing the immune system to still function properly, fight infections, and contribute to overall health. In prior studies, IMU-838 did not increase infection rate and also worked as an antiviral. In addition to PSC, researchers are also exploring IMU-838 as a potential treatment for multiple sclerosis (MS), COVID-19, and ulcerative colitis (UC).
In this particular study, whose enrollment was compromised by the COVID-19 pandemic, 18 patients were ultimately dosed; 11 finished the dosing. Patients received 30mg IMU-838 daily. The primary study outcome was to reduce ALP levels by 25% or more, while AST levels increased by no more than 33%. The secondary study outcomes were the analyze changes in AST, ALT, bilirubin, pro-inflammatory cytokines, and liver biochemistry parameters.
Ultimately, IMU-838 was shown to reduce ALP levels without significantly raising any other levels to a dangerous point. Additionally, the therapy seemed to reduce the burden of UC or IBD on patients, allowing for better outcomes and health improvement. The treatment was safe, effective, and well-tolerated. Researchers recognize that the patient sample size was small. Thus, more testing is needed. However, considering the potential benefits shown by IMU-838, researchers believe that it could offer a new and more effective treatment option for patients with PSC.
Primary Sclerosing Cholangitis (PSC)
Primary sclerosing cholangitis (PSC) is a chronic disease which causes bile duct damage. Normally, bile, a digestive fluid, moves from the liver to the gallbladder and small intestine. Through this process, bile plays a role in digestion. However, patients with PSC develop bile duct inflammation and scarring, which blocks the bile from moving and causes liver damage.
Though the exact cause of PSC is unknown, many believe that autoimmune dysfunction, toxin exposure, or viral or bacterial infections can cause this condition. Additionally, an estimated 75% of all patients with PSC have some form of inflammatory bowel disease (IBD). As the damage from PSC continues, patients may develop liver fibrosis, cirrhosis, and even liver failure. A majority of patients with PSC are male. There are no cures or treatments aside from surgery. Symptoms include:
- Extreme fatigue
- Severe itching (pruritus)
- Jaundice (yellowing of the skin and eyes)
- Abdominal pain, specifically in the upper right portion of the abdomen
- Fever and chills
- Unintended weight loss
- Liver and spleen enlargement
- Bile duct infection
- Liver failure
