Phase 3 data of BridgeBio Pharma’s heart disease drug have gone from “baffling” to elating, as new results extinguished a persistent flame of doubt encircling the biotech’s larger clinical development plans.
The company reported Monday that acoramidis had a “highly statistically significant” improvement on the primary endpoint, a hierarchy of assessments that included all-cause mortality, cardiovascular-related hospitalization and a six-minute walk test, among others. That grouping of endpoints was measured by a win-ratio of 1.8, better than the 1.7 figure representing an improvement in mortality and morbidity. When broken down by each individual assessment, all-cause mortality change was not statistically significant, with a p-value of 0.057.
On a call to discuss the results, BridgeBio’s head of cardiorenal Jonathan Fox, Ph.D., said it’s “too early to say” whether the lack of statistical significance specifically in all-cause mortality could hinder approval potential. CEO Neil Kumar, Ph.D., added that the primary endpoint was not powered to focus on each individual data point in the hierarchy informing the win ratio.
“It wasn’t an expectation that this would be [statistically significant] across everything,” Kumar said.
Generally speaking, the company and investors appeared bullish on the likelihood of approval. Shareholders seemed to agree, with the company’s shares beginning the day 60% up at $29.17 from a Friday closing price of $18.22.
Transthyretin amyloid cardiomyopathy is a rare heart muscle condition spurred by clumps of transthyretin protein buildup that is normally seen in older patients. More than four out of five patients treated with the drug lived at least 30 months, which BridgeBio noted was close to the survival rate for age-matched patients without the disease. There was a 50% relative risk reduction for the cumulative frequency of cardiovascular-related hospitalization.
The company did not provide exact figures on how acoramidis-treated patients faired on a six-minute walk test compared to placebo, the clinical arrow that punctured the company at an earlier interim readout. Previous results showing that placebo patients outperformed treated patients on the walk test were described by Kumar as “baffling.”
The number of side effects was high across the board, for both acoramidis and placebo, but there were more for the latter. BridgeBio found that 37.3% of treated patients had a severe treatment-emergent side effect, compared to 45.5% for placebo. Half of treatment-emergent side effects in patients given acoramidis led to hospitalization, compared to 60.7% for placebo.
Patients had the option to tack on Pfizer’s approved med Vyndaqel after a year into the trial, but there wasn’t a bevy of comparison data available. What the company did report hinted at potentially more upside, with acoramidis alone boasting higher serum TTR levels than placebo patients and Vyndaqel as well as lower levels of median NT-proBNP.
There was a palpable sense of relief on BridgeBio’s investor call, as the company can now plot commercial plans for its first cardiorenal drug. The biotech expects to submit an approval application to the FDA before the end of the year and additional filings including in Europe in the first half of 2024. Chief Commercial Officer Matt Outten called the drug a “commercial launch dream” on the investor call.
But the expectation, as said explicitly by one investor on the call, is that BridgeBio saddles up with a partner for at least some portion of the commercial launch. Kumar wouldn’t wholly commit to the prospect yet.
“With more potential launches over the course of the next 28 months here with our late-stage pipeline, and the work that we have done already in Europe … we’d be excited to launch the product there as well,” he said. But he noted that partnerships were one avenue the company could take to corral additional financing. Earlier this year, Bloomberg reported that the budding pharmaceutical company was drawing takeover interest.
Moving forward, BridgeBio is pressing ahead with phase 4, testing the drug as a primary prevention therapy. Kumar also teased the potential for a double-blind, head-to-head study against Vyndaqel in the future.