While the per protocol analysis should strengthen the conviction in obeticholic acid benefit in reversing histologic features of NASH in patients adhering to longer term treatment, the intent to treat analysis
provides a better integrated perspective on expected real-world benefit, accounting for missed doses, non-adherence, drug discontinuations and other contributors to the "significant" number of patients in Regenerate that didn't meet per protocol requirements, Birchenough tells investors in a research note.
The highest proportion of subjects achieving PGA Success in the Intent to Treat analysis
occurred at Day 42 with 26% of subjects in the AN2728 arm (n=46) achieving PGA Success compared to 18% in the vehicle arm (n=22).
Observed cases analysis using data on completers-a cherry-picked population-will almost inevitably have more positive results than an intent to treat analysis
of all patients, including scores of dropouts at the time of attrition (last observation carried forward, or LOCF).
By intent to treat analysis
at 48 weeks, 47% of patients in group C (quadruple therapy) had viral loads less than 50 copies/mL compared to 42%, 38% and 26% for groups A, B and D, respectively.
The study achieved its efficacy endpoints and other key measures at 12 weeks, including: On-treatment LDL-C lowering of an additional 18%, and in the intent to treat analysis
, LDL-C lowering of an additional 17%; Reduction of 19% in high-sensitivity C-reactive protein, an important marker of the underlying inflammation associated with cardiovascular disease; Reduction in hemoglobin A1c of 0.21% vs.
Blood samples that were taken every 2 weeks showed that the supplement significantly slowed the rate of PSA increase in both an intent to treat analysis
of 46 patients who had at least two serum PSA readings per treatment and an analysis of 42 patients who had five PSA readings per treatment as called for in the protocol.
The Program achieved its efficacy endpoints and other key measures at 12 weeks for bempedoic acid, including: on-treatment LDL-C lowering of an additional 18% to 31%, and in the intent to treat analysis
, LDL-C lowering of an additional 17% to 28%; reductions of 19% to 33% in high-sensitivity C-reactive protein, an important marker of the underlying inflammation associated with cardiovascular disease; reductions in hemoglobin A1c of 0.19% to 0.31% versus placebo in the subset of 1002 patients with diabetes.
In the intent to treat analysis
, LDL-C lowering was 32% for the combination pill compared to 3% for placebo, 21% for EZE and 18% for BA.
A modified intent to treat analysis
of 87 patients, which includes any patient who enrolled in the study and received at least one dose of study drug, was performed to evaluate the efficacy endpoints.