CymaBay Therapeutics, a biopharmaceutical company based in Newark, CA, develops and provides access to novel therapies with a recent focus on primary biliary cholangitis (PBC).
The company is currently developing seladelpar which is a selective, potent PPARδ agonist against PBC. PPARδ is a nuclear hormone receptor (a protein in cells) that regulates many biological processes.
PBC is a disease wherein the bile ducts are destroyed over time. Bile fluid, which is created in the liver, rids the body of toxins and aging red blood cells. Any damage to the bile ducts causes a back-up in the liver and could result in scarring of liver tissue (cirrhosis).
PBC mostly affects females and generally appears around middle age. It is considered to be a chronic autoimmune disease, but the cause of the disease has still not been established.
Inflammation in the liver begins when T cells (white blood cells) collect there. Normally T cells will defend against bacteria, but in PBC they destroy normal cells that line the liver’s small bile ducts.
If left untreated, the inflammation spreads to other parts of the liver. As the cells die they leave scar tissue that eventually leads to cirrhosis (scarring of liver tissue). Cirrhosis impedes the liver’s normal functions.
Perhaps the most common symptoms of early-onset PBC are pruritus (itching) and fatigue. A secondary endpoint of the ENHANCE trial is an evaluation of the effect of seladelpar on pruritus.
Progression of PBC may lead to liver cancer.
Seladelpar (MBX-8025) is being developed by CymaBay for patients with PBC. It is a selective, potent, and orally active peroxisome proliferator-activated receptor δ (PPARδ).
The drug was granted the Orphan Drug designation by the FDA and the EMA. Seladepar also received the Breakthrough Therapy designation from the FDA. The EMA granted the drug Priority Medicine status.
Results of the ENHANCE International Phase 3 Trial
CymaBay reported top-line results from the ENHANCE trial that evaluated the efficacy and safety of seladelpar to treat PBC. The drug reached its primary endpoint which was safety and efficacy. Seladelpar was found to be generally well tolerated.
The trial (NCT03602560 ) consisted of 240 PBC patients randomized to either a placebo, seladelpar 5mg, or 10mg once each day. Some of the patients enrolled in the trial received seladelpar 5mg for six months. The dosage was then increased to 10mg depending on tolerability for the rest of the (double-blind) period.
Upon completing the one-year period, participants may enter a longer-term safety study. This study is an “open label” study whereby the drug and dosage are made known to the participants and the doctors, unlike the double-blind studies.
CymaBay is committed to PBC patients and their families and its administration expressed appreciation for their participation in the ENHANCE study.