BridgeBio Pharma has been on the road to redemption ever since its treatment for a rare and fatal heart condition, acoramidis, flopped in an early readout of phase 3 data.
Three years since tripping over that hurdle, the Bay Area company is now revealing that at the end of that trial, acoramidis had reduced combined all-cause mortality and recurrent cardiovascular (CV)-related hospitalizations compared to placebo in patients with transthyretin amyloid cardiomyopathy (ATTR-CM).
“We are proud to share the results of this post-hoc analysis demonstrating a highly significant reduction in all-cause mortality and the sum of recurrent CV-related hospitalizations in patients with ATTR-CM at 30 months in the ATTRibute-CM trial,” Jonathan Fox, M.D., Ph.D., chief medical officer of BridgeBio's cardiorenal business, said in a Sept. 28 release.
The results were meant to be presented at the Heart Failure Society of America’s annual meeting in Atlanta, but the conference was canceled due to Hurricane Helene.
The ATTRibute-CM phase 3 trial began in 2019, enrolling 632 patients and testing 800 mg of acoramidis given orally twice daily. One of the primary endpoints of the study was the change in the distance that patients could walk in six minutes after a year of treatment. In December 2021, BridgeBio reported the surprising result that patients given placebo had bested patients in the treatment arm on this critical measure. The stunning outcome sent the company’s share price spiraling and led to two rounds of layoffs.
A 2022 oncology licensing deal with BMS put some wind back in BridgeBio’s sails, and further analyses of the ATTRibute-CM data began to paint a different picture of acoramidis. At the 30-month mark, patients given the drug were able to walk significantly farther in the six-minute walk test, survived longer and had a reduced risk of hospitalization. Data presented at the European Society of Cardiology meeting in August 2023 showed that nearly 15% of patients given treatment had a CV-related death, compared to 21.3% in the placebo group.
The crown jewel that eluded BridgeBio was a positive showing in all-cause mortality, with the earlier analyses not showing a significant effect on this measure. The overall relative risk reduction in all-cause mortality was 25% among patients given acoramidis compared to placebo, the company told investors in 2023, but the finding was not statistically significant.
In the canceled presentation, BridgeBio was set to announce a post hoc analysis revealing that acoramidis reduced the total number of all-cause deaths and recurrent cardiovascular hospitalizations by 42% compared to placebo in the ATTRibute-CM trial, according to the release.
In a Japanese trial run by Alexion, AstraZeneca Rare Disease, which has rights to commercialize the drug in Japan, acoramidis showed similar results, with improvements in survival, six-minute walk test and quality of life, BridgeBio said in the release.
“The reduction of hospitalizations and all-cause mortality seen in ATTRibute-CM heightens the case for acoramidis as a first-line therapy given its potential to improve the overall quality of life for patients,” Daniel Judge, M.D., a cardiologist at the Medical University of South Carolina who was set to present the results at the conference, said in the release.
BridgeBio has submitted acoramidis for approval with the FDA and the EMA, the company said. The FDA is slated to respond on Nov. 29, more than a year after the agency rejected acoramidis’ former competitor from Alnylam, Onpattro. Alnylam has since pivoted to another ATTR-CM candidate, Amvuttra (vutrisiran), which it is set to file for FDA approval after hitting all 10 of its primary and secondary endpoints in a phase 3 trial.
After BridgeBio's release, analysts at Evercore ISI wrote that there is not yet a "clear winner" between the two ATTR-CM prospects and Pfizer's approved tafamidis drugs. Treatment decisions "will likely be made by patient preference, route of administration and dosing frequency, patient out-of-pocket cost and economics to practice," the analysts concluded.