BridgeBio Receives FDA Green Light for ATTR-CM Medication, Igniting Rivalry with Pfizer

BridgeBio, along with patients suffering from transthyretin amyloid cardiomyopathy (ATTR-CM), has received good news following the FDA’s approval of acoramidis, which was announced on Friday evening, ahead of its scheduled Nov. 29 PDUFA date.

The launch of Attruby—a name assigned to the drug—initiates what could be a competitive landscape within the ATTR-CM market involving Pfizer’s tafamidis (Vyndaqel and Vyndamax) and Alnylam’s Amvuttra. Alnylam recently sought an expansion of its label for ATTR-CM in October.

Approval was backed by favorable outcomes from the Phase III ATTRibute-CM trial, in which the transthyretin stabilizer led to a notable decrease in cardiovascular-related hospitalizations and fatalities, along with an enhancement in patients’ quality of life.

Attruby is recognized as the “first and only approved therapy with a label indicating near-complete TTR stabilization,” as declared in a press release published by BridgeBio. Its labeling also emphasizes a decrease in the risk of hospitalization and death, a significant point with analysts highlighting the need for all-cause mortality benefits—which Attruby did not achieve in the ATTRibute-CM study.

This aspect is crucial, given that both tafamidis and Amvuttra have shown a statistically significant impact on all-cause mortality.

BMO Capital Markets analyst Kostas Biliouris noted, “The approval of Acoramidis with a CV mortality label positions it similarly to Tafamidis, representing a favorable scenario for investors.”

BridgeBio has set the price of Attruby at ,759.12 for a 28-day supply, translating to around 4,500 annually, as reported by Endpoints News. Furthermore, the company has pledged to provide Attruby at no cost for life to participants in its U.S. clinical trials.

Original article published Nov. 19:

ATTR-CM Approval for BridgeBio Could Trigger Tight Race With Pfizer

As the sole targeted treatment for transthyretin amyloid cardiomyopathy, Pfizer’s tafamidis—presented as Vyndaqel and Vyndamax—faces potential competition from BridgeBio’s acoramidis, pending FDA approval next week.

Acoramidis is a stabilizer of the transthyretin (TTR) tetramer and has a decision date set for Nov. 29. BridgeBio’s CEO, Neil Kumar, expressed optimism about the drug’s approval during an interview with BioSpace, stating, “This will represent our third approval, but notably our largest drug to date.”

The market for ATTR-CM, recognized as a rare but impactful cardiovascular condition, reached a valuation of .2 billion in 2023 and is projected to grow to .4 billion by 2031, according to InsightAce Analytic.

BridgeBio’s fate rests heavily on the success of acoramidis and its market entry, as noted by Kostas Biliouris, director of biotech equity research at BMO Capital Markets. The product is a focal point for BridgeBio alongside their targeted cancer treatment, infigratinib, still under development for achondroplasia.

Biliouris mentioned that acoramidis would be going up against Pfizer’s well-established tafamidis, presenting a challenging scenario for the smaller company.

A survey conducted among 30 physicians by BMO Capital Markets suggests a competitive field between the two treatments, with 50% rating acoramidis and tafamidis as “similar” in efficacy, and 40% believing acoramidis is “incrementally better.” A minority deemed acoramidis significantly superior, according to Biliouris.

If BridgeBio secures acoramidis’ approval, Biliouris estimated that the company would need to surpass U.S. sales expectations of around 5 million for 2025. “Exceeding this sales target would be beneficial for the company’s stock and narrative; failing could create challenges,” he stated.

A Decade of Progress

ATTR-CM is a serious condition that largely plagues the elderly, characterized by the misfolding of the TTR protein and resulting amyloid deposits that accumulate in heart muscle tissue, leading to rigidity in heart walls and impaired blood circulation.

Kumar likened ATTR-CM to “the Alzheimer’s of the heart” but highlighted that over the past 30 years, advancements have been made in addressing the disease before excessive TTR is deposited in the heart.

Previously, a decade ago, ATTR-CM often signified a dire prognosis. Now, Kumar pointed out, “Survival rates for patients on acoramidis closely resemble those of individuals without the condition, which is exceptional.”

In BridgeBio’s Phase III ATTRibute-CM study, acoramidis exhibited an 81% survival rate among participants, compared to 74% in the placebo group. The treatment also significantly halved the relative risk of cardiovascular hospitalizations, a finding reported in July 2023. Additional analyses shared in May during the 2024 International Symposium on Amyloidosis revealed a notable association between TTR reduction and increased survival rates.

While tafamidis achieves a 50% stabilization of TTR, Kumar indicated that acoramidis stabilizes it by around 96%. “We believe that our capacity to maximize the reduction of TTR deposits in the heart will lead to greater efficacy in treatment.”

However, a Pfizer representative countered, stating that tafamidis produces effects exceeding 90% on both TTR stabilization and relevant disease measures for its class.

Mortality Benefit Is Key

Biliouris acknowledged that acoramidis might be “incrementally better” than tafamidis, yet he cautioned that acoramidis presents challenges such as a need for more frequent dosing compared to tafamidis and the absence of a proven mortality reduction in trials—notably, tafamidis was approved in May 2019 due to its demonstrable enhancement in survival rates.

The ongoing discourse surrounding the data highlights concerns about the lack of a statistically significant all-cause mortality benefit in acoramidis’ ATTRibute-CM trial findings, as observed by Biliouris in a Nov. 11 investor note. While the primary endpoint of the trial was met, the significant secondary endpoint around all-cause mortality was not achieved. In contrast, tafamidis and Amvuttra have shown significant benefits in this aspect.

Nonetheless, BridgeBio presented updated findings from the open-label portion of ATTRibute-CM during the American Heart Association’s 2024 Scientific Sessions, indicating a statistically significant all-cause mortality advantage with acoramidis.

Drawing on insights from a previous clinical reviewer at the FDA, Biliouris expressed skepticism about acoramidis’ label reflecting a cardiovascular mortality benefit, projecting a potential 20%-30% downturn for the company.

In a Tuesday investor note, analysts from William Blair underscored the critical nature of a cardiovascular mortality benefit, insisting that a reduction in all-cause mortality is essential for gaining market share against tafamidis, which already carries mortality claims on its label.

Emerging Competition

The competitive environment for ATTR-CM could be expanding.

RNA therapies have exhibited noteworthy potential in treating the condition. Alnylam revealed promising data from its Phase III HELIOS-B trial of the RNAi therapy Amuvttra (vutrisiran) in June, demonstrating reduced risks of mortality and cardiovascular events in ATTR-CM. Leveraging this data, Alnylam submitted regulatory requests to both the FDA and the European Medicines Agency in October. Although Amvuttra is already authorized to treat hATTR amyloidosis, they aim to provide a viable alternative.

Mathew Maurer, a cardiology professor at Columbia University Irving Medical Center, noted that while Vyndaqel and Vyndamax can help slow disease progression, they do not offer reversibility. RNA therapies target the RNA to stop the production of mutated TTR proteins.

Alongside Amvuttra, Wainua (eplontersen), pioneered by AstraZeneca and Ionis, is being examined for ATTR-CM treatment in the Phase III CARDIO-TTRansform study.

Meanwhile, Intellia Therapeutics piqued analysts’ interests over the weekend at AHA by presenting Phase I data on the gene editor nexiguran ziclumeran (nex-z), indicating “rapid, deep and durable” reductions in TTR serum levels. A single dose of nex-z achieved a 90% mean reduction at 12 months, with observable signs indicating stabilization or improvement, even in patients with severe disease.

In a note, Biliouris described Intellia’s results as “robust,” suggesting favorable prospects for a successful PhIII outcome.

Analyst Joon Lee from Truist Securities lauded the data as “impressive,” pointing out that nex-z achieved a more considerable reduction in serum TTR levels compared to Amvuttra, along with a quicker onset of action.

Editor’s note (Nov. 20): This story has been updated with comments from Pfizer concerning tafamidis’ effectiveness.