An experimental medicine benefited patients with a deadly heart condition in a closely watched Phase 3 trial, lifting the fortunes of its developer, BridgeBio Pharma, and clearing the way for the biotechnology company to seek U.S. approval.
Trial results showed that more study participants with the condition, transthyretin amyloidosis cardiomyopathy, and treated with BridgeBio’s drug instead of a placebo were alive and out of the hospital after two-and-a-half years.
Treatment with the medicine, called acoramidis, also improved patients’ quality of life and heart health, according to data released by BridgeBio Monday. No new safety signals of “potential clinical concern” were observed, the company said.
Specifically, 81% of patients who received BridgeBio’s drug were alive at 30 months, compared to 74% of those on placebo — a reduction in the risk of death by about 6% in absolute terms and by 25% comparatively.
Acoramidis treatment had a stronger effect on hospitalization from heart problems, reducing the relative risk of that event by 50% versus placebo.
Daniel Judge, co-chair of the study's steering committee and a professor of medicine and cardiology at the Medical University of South Carolina, described acoramidis' benefits as "consistent and clinically meaningful” in BridgeBio’s statement.
The company intends to submit an approval application to U.S. regulators later this year.
The positive results help BridgeBio rebound from an earlier setback in the same trial. In December 2021, the company said acoramidis appeared to improve several surrogate measures of heart function after one year of treatment. But patients who received a placebo performed better on a walking test than past results had suggested, surprising the company and causing the study to miss one of its main goals. BridgeBio shares lost much of their value in the aftermath.
The biotech attributed the disappointing data to the better all-around care patients with TTR cardiomyopathy now receive. Caused by the toxic buildup of a protein that corrodes heart tissue, the disease is now identified earlier, when patients are less sick.
There is also an available treatment — a Pfizer medicine called Vyndamax — so patients are aware that drugs like acoramidis can help. In an interview in 2021, CEO Neil Kumar told BioPharma Dive “probably both factors” contributed to the study’s initial failure.
Pfizer’s drug, which generated more than $2 billion in sales last year, was approved on results showing it could reduce the risk of death and hospital stays.
Like Vyndamax, acoramidis is designed to stop the key protein involved in the disease — transthyretin or TTR — from misfolding. In preclinical testing, it did so more effectively than Vyndamax, raising expectations it might have a stronger effect on the disease.
While BridgeBio’s study missed its first goal, it continued to track patient outcomes on a composite measure of death from all causes, heart-related hospitalizations and several other markers of disease progression. Researchers calculated the result as a “win ratio,” a statistical method by which patients on a drug or placebo are compared on a variety of measures in a hierarchical fashion. When the outcome is the same in each patient pair — a “tie” — the comparison advances to the next measure.
BridgeBio said results showed a highly statistically significant result, with treatment associated with a win ratio of 1.8. That result is a “best-case scenario” and numerically superior to what was reported with Pfizer’s drug, wrote TD Cowen analyst Tyler Van Buren, in a Monday note to clients. Acoramidis is “a likely multi-billion-dollar drug,” he added.
Analyses of the different outcomes individually were also statistically significant, except for all-cause mortality, which narrowly missed that criteria.
BridgeBio hasn’t formally tested its drug against Pfizer’s, making it harder to compare across study results. Still, the company cited data from an exploratory analysis in a smaller number of patients in the study who later took Vyndamax. They suggested a stronger relative effect for BridgeBio’s drug on key disease markers, although that finding isn’t conclusive.
More detailed study results will be presented at a medical meeting next month. BridgeBio shares surged 86% higher in trading Monday, approaching levels last reached in late 2021.
The results are significant for other developers of TTR cardiomyopathy medicines, too. Alnylam Pharmaceuticals has two drugs in Phase 3 testing that are meant to “silence” the gene that produces the misfolded protein, rather than stabilize TTR.
One, an infused medicine called Onpattro, is currently being reviewed by regulators after proving beneficial on a walking test in a late-stage trial. It hasn’t yet been proven to extend lives, though testing is ongoing.
Ionis Pharmaceuticals and Intellia Therapeutics are also testing drugs in clinical trials.