In a news release from August 10, 2021, biotechnology company CohBar, Inc. shared that positive topline results were available from a Phase 1a/1b clinical trial evaluating CB4211 for patients with nonalcoholic steatohepatitis (NASH) and obesity. CohBar, which develops unique treatment solutions using mitochondria, believes that CB4211 shows promise for reducing serums ALT and AST, and improving patient outcomes, for those with NASH.
To begin, what exactly is CB4211? According to CohBar, CB4211 is:
a novel peptide initially developed from a MOTS-c mitochondrial derived peptide [MDP].
In short, this analog was first discovered by CohBar around 9 years ago and has been in development to improve the lives of those with NASH. This is especially important as there are no FDA-approved treatments available for patients. Thus, CB4211 has the potential to fill a huge unmet need. Additionally, CB4211 is the first-ever mitochondria-based therapy to ever reach the stage of clinical testing!
Within the Phase 1a/1b clinical trial, researchers evaluated the safety, efficacy, tolerability, and pharmacokinetic profile of CB4211. Altogether, 65 healthy volunteers enrolled. During the first portion of the trial, researchers worked to determine an appropriate CB4211 dosage for further testing. Ultimately, this was determined to be 25mg CB4211 administered subcutaneously 1x daily for a 4-week period. During the second portion of the trial, 20 patients with nonalcoholic fatty liver disease (NAFLD), who were also obese, enrolled. To participate, patients must have had 10% or more liver fat. Findings from the study included:
- CB4211 was relatively safe and well-tolerated. Although some adverse reactions did occur, the most common adverse reactions were injection site reactions.
- Altogether, there were significant reductions in both serum ALT (-21%) and serum AST (-28%), as well as glucose (-6%). Since this occurred over a 4-week period, this highlights the potential of both fast and effective liver support for patients.
- Through evaluating the pharmacodynamics, researchers highlighted biomarkers which showed reductions in liver damage. Liver fat was also reduced in both patients receiving CB4211 (-5.03%) and the placebo (-4.88%). Approximately 36% of patients taking CB4211 saw over a 30% relative reduction of liver fat content.
- Finally, CB4211 helped patients move towards a lower body weight, showing efficacy for treating both NASH and obesity.
Nonalcoholic Steatohepatitis (NASH)
Unlike liver disease that affects heavy drinkers, nonalcoholic steatohepatitis (NASH) occurs in patients who do not drink – or drink very little. However, NASH mimics the symptoms of alcoholic liver disease, including the over-accumulation of fat in the liver. As this fat builds up, it causes inflammation and, in some cases, scarring (fibrosis). As a result, NASH may cause reduced liver function or a host of other health issues. Doctors believe that risk factors for NASH include having high cholesterol, being obese, or having type 2 diabetes or a metabolic syndrome. Altogether, an estimated 25% of Americans have NASH. If symptoms appear, these include:
- Nausea and vomiting
- Appetite loss
- Jaundice (yellowing of the skin and eyes)
- Pruritus (intense itching)
- General malaise and bodily weakness
- Confusion or cognitive impairment
- Unintended weight loss
- Abdominal pain or swelling