New PBC therapy found to reduce liver scarring after 1 year in US trial
CNP-104 shows promise for improving liver health in primary biliary cholangitis
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Use of the experimental immune-modulating therapy CNP-104 in adults with primary biliary cholangitis (PBC) participating in a U.S. clinical trial led to greater reductions in markers of liver damage and scarring, or fibrosis, compared with a placebo after one year.
That’s according to new data from the Phase 2a trial, which is testing Cour Pharmaceuticals‘ therapy candidate in a small number of people with PBC, an immune disease that affects the liver.
“These results spanning both … fibrotic and [liver damage] biomarkers support the potential of CNP-104 as a novel therapeutic option of PBC and inform our ongoing evaluation of the program’s development strategy, including potential collaboration with a strategic partner,” Dannielle Appelhans, CEO of Cour, said in a company press release announcing the positive results.
Cour’s announcement did not include many specifics; the company expects to present full one-year data at a future scientific meeting.
PBC is an autoimmune disease marked by inflammation of the bile ducts, a series of tubes that carry bile, a digestive fluid, from the liver to the intestines. Inflammation of these tubes leads to cholestasis, in which bile flow is stalled or stopped. This causes bile to build up in the liver, which can lead to liver fibrosis that interferes with the organ’s function.
CNP-104 designed to retrain body’s immune system
Essentially, the body’s immune system sees the world in black and white: Anything that’s a healthy part of the body should be left alone, and everything else is assumed to be a threat and is attacked. The immune system’s ability to distinguish self from non-self is known as immune tolerance, and a breakdown of this tolerance is what basically drives autoimmune diseases.
In PBC, this means that the immune system begins to attack healthy bile duct cells as if they were foreign invaders. In almost all patients, this autoimmune attack is driven by self-reactive antimitochondrial antibodies, which target a complex of proteins called the pyruvate dehydrogenase complex. Specifically, these antibodies bind to the E2 subunit of this protein complex.
CNP-104 uses tiny, protein-filled particles designed to retrain the immune system. These particles are taken up by immune cells, which are then trained to view the E2 subunit as a normal part of the body rather than a foreign threat, effectively restoring tolerance.
The therapy has received orphan drug and fast track designations in the U.S. for the treatment of PBC. These statuses are meant to accelerate a treatment’s clinical development and regulatory review, with the goal of getting new medicines to patients more quickly.
1-year trial data confirm stabilization of liver stiffness
The proof-of-concept Phase 2a trial (NCT05104853) enrolled 42 adults with PBC who were not responsive to the first-line therapy ursodeoxycholic acid (UDCA, sold as Urso, Actigall, and generics) and/or Ocaliva (obeticholic acid). Ocaliva is a second-line PBC therapy that was withdrawn from the U.S. market last year due to safety concerns.
Trial participants were randomly assigned to receive two infusions of either CNP-104 or a placebo, administered one week apart. All participants are being followed for up to two years.
Cour previously announced top-line four-month data showing that treatment with CNP-104 altered the activity of immune cells toward immune tolerance and in an antigen-dependent manner. Antigens are proteins targeted for immune attack.
The infusion therapy was also associated with a significantly greater reduction in liver stiffness, used as a proxy of liver fibrosis, relative to the placebo.
The company now reports that, after one year, CNP-104-treated patients continued to show significantly less liver stiffness than those given the placebo. A greater proportion of patients given the therapy also achieved a composite biochemical response, which is based on levels of certain liver damage markers in the blood.
Participants given the medication also showed an improvement in the UK-PBC prognostic risk score, a validated tool that predicts the risk of liver failure or death in PBC patients, according to Cour.
“CNP-104 demonstrated robust antigen-specific immune modulation consistent with restoration of immune tolerance in PBC, as shown in the previously announced day 120 analysis,” Appelhans said. “The one-year data confirms continued stabilization in liver stiffness measurements and validated prognostic risk scores, while newly demonstrating achievement of established composite biochemical response criteria at twelve months.”
According to Cour, the “one-year findings show durable clinical effects.”
Further, safety data showed CNP-104 was generally well tolerated, with no reports of serious side effects related to the therapy.
