On a Zoom call last month from California, BridgeBio CEO Neil Kumar needled a colleague about the remote possibility of the New York Yankees rallying to win the World Series as they trailed the Los Angeles Dodgers three games to one.
After describing his own company’s improbable comeback from a disastrous interim trial result in 2021 to advance the drug to the verge of an FDA approval, Kumar zinged his New Jersey-based associate.
“This will be a good story,” Kumar said of BridgeBio’s revival. “Unlike the Yankees.”
Kumar was correct, both about the Yankees—who lost the series that night—and about his company’s comeback story, which came complete on Friday when the FDA signed off on Attruby (acoramidis), a potential blockbuster to treat patients with the rare heart disease transthyretin amyloid cardiomyopathy (ATTR-CM).
With the nod, BridgeBio will challenge Pfizer’s powerhouse Vyndaqel (tafamidis) franchise, which dominates the indication, generating (PDF) worldwide sales in the first three quarters of this year of $3.9 billion.
BridgeBio will take on Pfizer with an advantageous label explaining that the pill reduces the risk of both death and hospitalization. Analysts from Evercore ISI and Mizuho Securities called the label a “best-case” outcome for the company.
The label is “effectively identical” to Pfizer's tafamidis, according to Mizuho’s Salim Syed.
“As the PDUFA date was nearing, this became debate item No. 1 for investors, hence, having this should provide relief to investors and the stock,” Syed added. By mid-morning on Monday, BridgeBio's stock price was up 27%.
The approval comes for a company that saw its share price plummet by more than 80% when highly touted acoramidis came up short in an interim report from a phase 3 study as patients on placebo bested those who received the treatment in a six-minute walk test.
But after executing two rounds of layoffs, BridgeBio retooled and recovered. In July of last year, the company revealed trial data that showed acoramidis’s ability to keep patients alive longer and reduce their trips to the hospital.
Last week, BridgeBio released results of an open-label extension study of the trial which showed that acoramidis provided reductions of 36% and 34% in all-cause mortality (ACM) at months 36 and 42, respectively, versus placebo. In the composite endpoint of ACM and recurrent cardiovascular-related hospitalizations, acoramidis delivered reductions of 46% and 48% at months 36 and 42, respectively.
The trial also eventually showed a positive affect in the distance patients could cover in their six-minute walk test.
“What happened over the course of a decade since Pfizer ran their trials and when we ran our trial was that—absent pharmacologic intervention—people just got better at caring for these individuals,” Kumar said on last month's call. “It’s not that our drug failed at 12 months, it’s just that no one got sick. We needed to go out longer to have the placebo arm decline so that we could show the effects of our drug.”
BridgeBio has placed a $18,759 price tag on Attruby for a 28-day supply, which works out to roughly $244,000 annually. Pfizer charges approximately $268,000 for Vyndaqel and Vyndamax before discounts per year, a price that drew criticism last month from the Institute for Clinical and Economic Review.
“We were expecting (Attruby) to be priced at parity,” Evercore ISI analyst Cory Kasimov wrote in a note to clients. “Management acknowledged that their extensive market research suggested they make it easy for prescribers and ‘do the right thing.’ A lower price won’t impact patient out of pocket costs (will be very low), but it can impact prescriber perception.”
BridgeBio and Pfizer’s products are transthyretin (TTR) stabilizers, which reduce the misfolding of TTR monomers that clump together and can build up in the left ventricle, causing heart failure. BridgeBio contends that Attruby stabilizes TTR more completely.
“You can turn the faucet off halfway—and that’s what tafamidis does—or you can turn it off fully, or 95% of the way, and that’s effectively what we’re doing,” Kumar explained. “What you can see from the genetics is, the more you turn that faucet off, the better it is for patients and obviously we’ve demonstrated that clinically.”
Pfizer takes issue with Kumar’s portrayal of tafamidis, pointing to a 2023 in vivo study, published in Amyloid, which said that the approved dose of Vyndamax/Vyndaqel was “estimated to reduce unbound TTR tetramer by 92%.”
BridgeBio said that the findings from the paper “describe a tafamidis binding model based on plasma samples from healthy volunteers, but do not represent stabilization in patients.”
The company also cited experiments by independent laboratories from the phase 3 ATTRibute-CM trial comparing the extent of TTR stabilization between acoramidis and tafamidis, which concluded that “stabilization was significantly greater for acoramidis than for tafamidis even at its peak clinical concentration.”
When Pfizer’s products were developed, there were concerns that “super-stabilization might cause its own problems,” Kumar added. But several years ago, a cardiologist in Portugal, Teresa Coelho, made key discoveries through genetic sequencing of a “rescue mutation,” which showed the value of complete stabilization.
“We dropped in on the opportunity at the exact right time,” said Kumar, who founded BridgeBio in 2015. “We were fortunate in that respect.”