AMSTERDAM –
The drug, acoramidis (BridgeBio Pharma), showed a significant reduction, compared with placebo, in the primary endpoint, a hierarchical analysis of all-cause mortality, cumulative frequency of cardiovascular hospitalizations, and change from baseline in N-terminal of the prohormone brain natriuretic peptide (NT-proBNP) and 6-minute walking distance, in the ATTRibute-CM trial.
The combination of all-cause mortality/cardiovascular hospitalization was also significantly reduced.
The trial was presented at the annual congress of the European Society of Cardiology by Julian Gillmore, MD, head of the University College London Centre for Amyloidosis.
“ATTRibute-CM was a robustly positive trial, showing benefits across the board for acoramidis, and suggest the tantalizing possibility of genuine clinical improvements,” Dr. Gillmore concluded.
ATTR-CM is a debilitating and progressive condition that increases mortality and reduces quality of life. Although this form of cardiomyopathy was considered to be very rare not long ago, improvements in imaging techniques and treatment developments have resulted in an upsurge in diagnosis throughout the world, and the disease is being diagnosed at an earlier stage, Dr. Gillmore noted.
ATTR-CM results from aggregation and deposition of transthyretin amyloid fibrils in the heart and various tissues. Acoramidis stabilizes the TTR tetramer and avoids the production of the fibrils.
Another similar drug, tafamidis (Vyndaqel, Vyndamax, Pfizer), was approved by the Food and Drug Administration in 2019 for ATTR-CM and is now available in several counties, including Japan and Europe.
BridgeBio Pharma is planning to file for FDA approval for acoramidis toward the end of 2023 and in other countries in 2024, Dr. Gillmore reported.
“It will be a huge benefit to patients to have another effective drug available,” he said.
Tafamidis also showed impressive results with its pivotal trial – ATTR-ACT – including a significant reduction in all-cause mortality, which was not seen in the ATTRibute-CM trial with acoramidis.
Asked about this, Dr. Gillmore replied: “It is difficult to comment on comparison with tafamidis as there isn’t a head-to-head trial. All I can say is that these results with acoramidis are fantastically encouraging, and I think we are going to have two effective drugs to treat this progressive and fatal condition.”
He elaborated that the difference in all-cause mortality results between the trials was “entirely consistent” with differences in the trial populations, with the ATTRibute-CM trial recruiting much lower-risk patients, in line with the earlier diagnosis of the condition that is now occurring.
“The survival in the placebo group in the ATTRibute study was greater than that in the treatment group in the ATTR-ACT study. So, it’s not all that surprising, given the reduced number of events, that mortality alone was not statistically significant in ATTRibute. What is important is that the trend in mortality was in the right direction, with an impressive risk reduction,” Dr. Gillmore noted.
“Incredibly, survival at 30 months and hospitalization rates among patients receiving acoramidis approached that of age-matched individuals who do not have ATTR,” he added.
Noting that more patients in the placebo group started taking tafamidis during the trial, Dr. Gillmore suggested that this would be expected to dilute the treatment effect of acoramidis.
“To have such a strongly positive study despite the change in the patient population and drop-in use of tafamidis is incredibly powerful,” he concluded.