RE GLMD: Aramchol P2b (300, 600 mg, placebo) data from ARREST in June, MRI/MRS and biopsy, 52w. Due to small MC ($80M) and with some probability for positive, (I early mentioned that, IMW, Aramchol is not well design molecule for liver targeting, it may be safe up to 600 mg dose-endogenic components), it may be speculative play. Downside is significant, sub-cash level (<$19M).
If bempedoic Acid (BA, ESPR) can generate so much false excitement (IMO) on LDLc battlefield, why would Aramchol be any different for NASH???
PS: In today CC they again did not explain ARRIVE failure. "ARRIVE was a small investigative initiative trial in a very distinct population, whose pathogenesis is slightly different from common NASH. HIV patients have advanced liver disease, which is a major cause for morbidity and mortality. All those pathology fatty liver is similar to common NASH, a pathogenesis involved in HIV lipodystrophy NAFLD is different and multi-factorial including the effect of the (inaudible) cell and the anti-HIV medication."
From the Aramcol mechanistic characterization and PD/PK ( ncbi.nlm.nih.gov ): 1) stearoyl-CoA desaturase 1 downregulation (SCD1)/ triglyceride level reduction and 2) promoting cellular redox homeostasis by enhancing GSH/GSSG ratio,
I do not see reasons why would compound act differently in HIV NAFLD relative to NASH????
Speculative maybe: due to concomitant HIV medication, liver enzymatic activity is enhanced and methabilizam/destruction of the Aramchol accelerated. Drug level in liver reduced???
IF anyone have any insight on topic, please respond. |
