Chemomab Therapeutics announced new plans yesterday, following positive results from their Phase 2 SPRING Study testing a drug called CM-101, recently assigned the name nebokitug. The plans for a Phase 3 trial of nebokitug in PSC were developed in collaboration with experts and the U.S. FDA.

Primary sclerosing cholangitis is a long-term liver disease that can affect people of any age. People with PSC have a faulty immune system that mistakenly ‘attacks’ the bile ducts (small tubes that drain bile out of the liver). This leads to inflammation and fibrosis (scarring) in the bile ducts and liver and can eventually lead to liver failure.

Chemomab’s drug, nebokitug, blocks the activity of CCL24, a protein involved in the development of inflammation and fibrosis in the bile ducts in PSC. Participants in the SPRING trial treated with nebokitug, especially those with moderate/advanced disease, showed improvements on a wide range of PSC-related disease markers including inflammation and fibrosis markers (such as routine liver blood test results, Fibroscan measurements and Enhanced Liver Fibrosis (ELF) scores).

Chemomab is now planning a larger study to more fully understand how nebokitug helps people with PSC.

Pivotal Phase 3 Study in PSC

Phase 3 trials are studies that typically involve more participants and are used to confirm the Phase 2 trial results and potentially to advance to regulatory agency review and approval. Chemomab’s Phase 3 study will be what is known as a ‘pivotal study’.

This means that it will be designed to provide the necessary data that the US regulatory agency, the FDA, needs to decide if nebokitug is safe and effective enough to be prescribed to people with PSC.  As with other such agencies around the world, the FDA has strict standards and requirements about the evidence they need to approve new drugs, and this can take many years and additional studies.

New Trial Design

The Phase 3 study will focus on how nebokitug impacts complications associated with PSC progression. Because of the positive results seen in the Phase 2 SPRING study, it is hoped that the nebokitug will delay PSC complications for people who take it. The Phase 3 trial will be designed to assess this.

The Phase 3 study will focus on how nebokitug impacts complications (also known as clinical events) associated with PSC progression. Because of the positive results seen in the Phase 2 SPRING study, it is hoped that the nebokitug will delay and even reduce occurrence of PSC complications for people who take it. The Phase 3 trial is designed to assess this.

In the past, Phase 2 studies looking at drugs to treat PSC have assessed how effective drugs are by looking at changes in surrogate markers. These are markers that can be measured now that are thought to predict future outcomes. They help speed up trials which could take decades if they waited to see if the treatment actually improved outcomes. In PSC, examples include alkaline phosphatase (ALP) in liver blood test results and liver biopsy results. The problem in PSC is that we are not certain that these surrogate markers really do predict outcomes for people with PSC. This makes clinical trials in PSC challenging.

The Phase 3 trial for nebokitug in PSC is looking at its actual impact on patients’ lives: measuring the length of time it takes for certain complications to occur. These complications include:

• acute cholangitis
• portal hypertension (increased blood pressure in the large vein that brings the blood and absorbed nutrients from the intestine to the liver)
• hepatic decompensation (when the damaged liver is no longer able to function properly)
• increased MELD score (a measure associated with the need for liver transplant in some countries)
• liver transplantation
• some cancers
• death.

The study will also record liver blood tests, scan results and quality of life/ symptom changes.

Enrolled participants will remain in the trial until they experience a complication, and the whole trial will continue until a pre-specified number of events has been recorded (about two years).

What's next?

The new trial is not recruiting yet. Planning is now underway and enrollment could start as early as the end of 2025 in the USA. Look out for PSC Support announcements for updates on nebokitug.