The curse of raised liver enzymes has struck again, with Third Harmonic the latest company to discontinue a phase 1b study of its lead asset over two reports of liver toxicity.
The news sent the biotech’s shares plummeting 75% in premarket trading to $4.96 apiece from a Wednesday closing price of $19.80.
The trial in an inflammatory skin condition called chronic inducible urticaria was designed to evaluate the safety, efficacy and pharmacokinetics of three dose levels of the drug, dubbed THB001, over 12 weeks of treatment. Five subjects were enrolled in the first cohort of two 200-mg doses a day, with the second and third participants showing raised levels of the liver enzymes alanine transaminase (ALT) and aspartate transaminase (AST) at their week eight study visits.
All other laboratory and diagnostic measures indicated no change in liver function for either individual and neither one experienced any symptoms related to the raised levels, the company pointed out. The raised enzyme levels had not been observed in a phase 1a study of THB001, and Third Harmonic said it is beginning non-clinical studies to identify the mechanism that caused them.
Raised levels of ALT and AST have plagued clinical trials this year, forcing both Centessa Pharmaceuticals and Surrozen to drop their respective alpha-1 antitrypsin deficiency and colitis studies.
With its lead asset seemingly sidelined, Third Harmonic tried to keep spirits up by promising to nominate a development candidate next year from its program of inhibitors for KIT, a cell surface receptor that serves as the master regulator of mast cell function and survival.
“While this is a deeply disappointing outcome, we are encouraged by the preliminary signs of clinical activity at this starting dose and are optimistic about the potential for a selective oral wild-type KIT inhibitor to become an important treatment modality 10for mast cell-driven inflammatory diseases,” Third Harmonic CEO Natalie Holles said in a release Thursday morning.