Stock Watch: Bridgebio’s Endpoint A Bridge Too Far

The announcement of the results of the 12-month Part A component of BridgeBio Pharma, Inc.’s ATTRibute-CM study of acoramidis (formerly AG10), in 632 symptomatic transthyretin amyloid cardiomyopathy (ATTR-CM) patients, was supposed to provide a mandate for regulatory submissions. This was because the primary endpoint in the Phase III ATTRibute-CM study was a hard clinical measure – the six-minute walk distance (6MWD). This contrasted with the trial on which Biogen, Inc., gained a much contested and mostly un-reimbursed accelerated approval on the basis of a surrogate marker of disease.

The mean observed decline in 6MWD after 12 months was just over 9 meters for patients treated with acoramidis. This was worse than the average 7-meter decline in placebo-treated patients. The failure of the primary endpoint was described as “disappointing and baffling” in light of secondary surrogate endpoints which moved in favor of acoramidis, the absence of any baseline imbalances between the active and placebo arms, and the study appearing to have been conducted well, without any hindrance from the pandemic. Adding to Bridgebio’s bafflement was a similar baseline enrollment profile of the patients in the ATTRibute-CM study to those in Pfizer Inc.’s* ATTR-ACT Phase III study of Vyndaqel (tafamidis), where Vyndaqel met the primary mortality endpoint at 30 months