ANX1502 tablet shows promise in proof-of-concept CAD trial
Therapy to thwart abnormal complement-mediated autoimmune responses
Annexon Biosciences’ new tablet formulation of its experimental therapy ANX1502 reduced key clinical and biomarker measures in the three cold agglutinin disease (CAD) patients so far enrolled in a proof-of-concept clinical trial.
“In patients treated with the oral small molecule ANX1502, we are encouraged by the changes in multiple measures of hemolysis [red blood cell destruction],” Douglas Love, president and CEO of Annexon, said in a company press release. “Our ongoing ANX1502 proof-of-concept (POC) trial is designed to build a robust dataset in up to seven patients with data expected mid-2025.”
No details about where the trial is being conducted were disclosed.
In CAD, self-reactive antibodies called cold agglutinins bind to red blood cells at low temperatures, activating the classical complement cascade, a group of immune proteins, that drives hemolysis and subsequent CAD symptoms.
What is ANX1502 and how does it work?
ANX1502 is a first-in-class oral therapy that suppresses the active form of the complement protein C1s, which together with the C1q complement protein triggers classical pathway activation. By blocking the pathway, the treatment should reduce or prevent the abnormal immune responses that drive CAD and other complement-mediated autoimmune diseases. In CAD, this would reflect in less or no hemolysis and a reduction in symptoms.
Annexon originally developed a liquid formulation of ANX1502, whose safety, tolerability, and pharmacological properties were evaluated in a Phase 1 trial (NCT05521269).
Single ascending doses (25 to 1,050 mg) and multiple ascending doses (200 to 525 mg twice daily for 14 days) were tested against a matching placebo in 84 healthy adult volunteers.
Data showed ANX1502 reached target levels in the blood of participants who received either single or multiple ascending doses. Higher single doses (525 to 1,025 mg) decreased blood levels of C4d, a marker for classical complement activation, in those who initially had higher than median levels.
Also, the therapy’s pharmacokinetics, or movement into, through, and out of the body, supported twice-daily dosing in future trials.
ANX1502 was generally well tolerated at all doses, with gastrointestinal problems, including nausea, vomiting, and diarrhea, being the most common side effects.
Annexon’s new tablet formulation of ANX1502 was designed to improve tolerability and patient experience, according to the company. The tablets are enteric-coated, which prevents the medication from being released until it reaches the small intestine. This allows flexible dosing to achieve blood ANX1502 levels four to five times above target concentrations.
The ongoing trial is assessing ANX1502’s tolerability, pharmacokinetics, and pharmacodynamics, or effects on the body, in up to seven patients. Clinical efficacy goals include a reduction in hemolysis, as indicated by a drop in blood levels of bilirubin, a yellowish pigment produced when red blood cells break down.
Newly announced early data from the first three participants showed ANX1502 tablets reduced clinical and biomarker measures consistent with complement suppression and less hemolysis.
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