From the Guidelines
Chemomab Therapeutics is developing CM-101, a first-in-class monoclonal antibody targeting CCL24 (eotaxin-2), as a potential treatment for Primary Sclerosing Cholangitis (PSC), which has shown promising results with a favorable safety profile and potential anti-fibrotic and anti-inflammatory effects in clinical trials 1. PSC is a chronic liver disease characterized by inflammation and fibrosis of bile ducts, for which there are currently no FDA-approved therapies.
Key Points
- CM-101 works by blocking CCL24, a chemokine that promotes inflammation and fibrosis in the liver.
- The drug received Fast Track designation from the FDA for PSC treatment and is currently in Phase 2 clinical trials.
- If successful, CM-101 could address a significant unmet need for PSC patients who currently rely on symptomatic management and ultimately liver transplantation as the disease progresses.
- The mechanism of targeting CCL24 represents a novel approach to addressing the underlying inflammatory and fibrotic processes in PSC rather than just managing symptoms.
- Patients with PSC should discuss with their hepatologists about potential eligibility for clinical trials involving CM-101 or other emerging therapies, as standard treatment options remain limited.
Emerging Therapies
- Other emerging therapies for PSC include bezafibrate, which has been shown to have antipruritic and anticholestatic effects in clinical trials 1.
- Rifampicin is also recommended for the treatment of moderate to severe pruritus in sclerosing cholangitis 1.
- Novel medical antipruritic strategies include the application of non-absorbable inhibitors of the ileal apical sodium bile salt transporter (ASBT encoded by SLC10A2) and selective PPARα or PPARδ agonists 1.
Current Guidelines
- The current guidelines for the treatment of PSC recommend against the use of corticosteroids or immunosuppressive therapies in people with PSC with mildly elevated serum IgG4 (<2x ULN) 1.
- Long-term use of antibiotics is not recommended for treatment of PSC in the absence of recurrent bacterial cholangitis 1.
- Pharmacological treatment of moderate to severe pruritus in sclerosing cholangitis with bezafibrate or rifampicin is recommended 1.
From the Research
Emerging Therapies for Primary Sclerosing Cholangitis (PSC)
There are several emerging therapies for the treatment of Primary Sclerosing Cholangitis (PSC), including:
- Modulation of bile composition
- Immunomodulation
- Targeting the gut microbiome
- Targeting fibrosis 2
- Novel pharmacological agents such as norursodeoxycholic acid, nuclear receptor agonists, anti-fibrotics, antibiotics, and anti-inflammatory drugs 3
Chemokine Antibody (Chemomab) Therapies
However, there is no direct evidence of the use of Chemokine Antibody (Chemomab) therapies for the treatment of PSC in the provided studies.
Current Treatment Options
Currently, liver transplantation is the only treatment modality shown to prolong survival in PSC patients 4, 3, 5, 6. Endoscopic therapy is indicated for symptomatic dominant strictures and in the work-up of malignancies 3, 5. Ursodeoxycholic acid (UDCA) has been extensively studied in PSC but failed to show a positive impact on the natural course of the disease 5, 6.
Future Directions
Successful PSC therapy will likely be a personalized combination of different drugs plus endoscopic treatment 2. Several investigator-initiated studies and innovative clinical trial programs are underway to develop effective medical treatments for PSC 4.