BridgeBio Pharma, Inc. announced the publication of new analyses in Circulation: Heart Failure, examining kidney function in individuals with transthyretin amyloid cardiomyopathy (ATTR-CM) treated with acoramidis. The publication, based on post-hoc analyses of data from randomized, double blind, placebo-controlled trials including the Phase 2 study and the Phase 3 ATTRibute-CM study, revealed that acoramidis initiation was associated with direct kidney-protective effects. The findings are significant as kidney dysfunction is an independent predictor of mortality in ATTR-CM, and these effects have not been reported with other approved ATTR-CM therapies.

The post-hoc analyses demonstrated that acoramidis was associated with an early, reversible estimated glomerular filtration rate (eGFR) dip of 8.5±0.48 mL/min/1.73 m² (95% CI: 7.57, 9.44). This dip was accompanied by a reduction in placebo-corrected urinary albumin to creatinine ratio (UACR) by 15.5% by Day 28 (P<0.05). The magnitude of the acute eGFR dip was positively associated with a reduction in early cardiovascular outcomes, whereas the opposite was observed with placebo.

Treatment with acoramidis provided a sustained, improved chronic eGFR slope of +2.47 mL/min/1.73m²/year (p<0.001) and a sustained UACR reduction of 13.7% (p=0.026) through Month 30. The profile observed was consistent with drugs that act directly on the kidney, such as ACE inhibitors, ARBs, and SGLT2 inhibitors. This supports a direct kidney mechanism that is potentially independent of TTR-stabilization.

Participants with eGFR dips larger than the overall population median experienced a 58% lower risk of death or cardiovascular hospitalization (HR: 0.42; 95% CI, 0.22–0.78; P=0.006) and a 66% lower risk of hospitalization alone (HR: 0.34; 95% CI, 0.17–0.66; P=0.002) in the first year of treatment. Within the placebo arm, eGFR dips were associated with worse outcomes. The acute, reversible eGFR dip following acoramidis initiation reflects a favorable hemodynamic renal response that may help explain the early separation in cardiovascular outcomes versus placebo.

Key Findings from Post-Hoc Analyses

Acoramidis is approved as Attruby® by the U.S. FDA and as BEYONTTRA® by the European Medicines Agency (EMA), Japanese Pharmaceuticals and Medical Devices Agency, Swissmedic, the UK Medicines and Healthcare Products Regulatory Agency, and the Brazilian Health Regulatory Agency (ANVISA). All labels specify near-complete stabilization of TTR. The most common adverse reactions reported in patients treated with Attruby versus placebo were diarrhea (11.6% vs 7.6%) and upper abdominal pain (5.5% vs 1.4%).

BridgeBio Pharma has entered into an agreement to raise up to $1 billion in newly issued convertible preferred equity from funds managed by Sixth Street and HealthCare Royalty, a business of KKR. The financing strengthens the company's balance sheet to support current and upcoming product launches, including potential U.S. approvals for three therapies over the next 12 months. These therapies include BBP-418 for LGMD2I/R9, encaleret for ADH1, and infigratinib for achondroplasia, alongside the continued growth of Attruby.

Sixth Street acted as the lead investor, funding $800 million, while HealthCare Royalty contributed $133.9 million at the close of the investment. Neil Kumar, Ph.D., Co-Founder and CEO of BridgeBio, stated that the capital ensures the company can deliver on its mission of launching medicines while maximizing economic value.

Key Investment Terms

The Series A Cumulative Convertible Participating Preferred Stock features a 7.00% initial dividend, payable in kind or in cash at BridgeBio's election. The initial conversion price is set at $137.79 per share, a premium of more than 100% to the company’s 30-day volume-weighted average price. This price increases to $153.10 per share, representing a premium of over 125%, starting from the fifth anniversary. The equity is permanent with no scheduled maturity and no redemption at the holder's option, though BridgeBio may redeem the stock for cash or convert it into common stock under specific terms.

Jeff Pootoolal, Partner at Sixth Street, highlighted the firm's support for BridgeBio during this stage of potential approvals and launches. Clarke Futch, Chairman and CEO of HealthCare Royalty, cited the management team's track record in developing life-changing therapies as a key factor in the partnership. Latham & Watkins LLP advised BridgeBio, while Sullivan & Cromwell LLP and Mintz LLP advised Sixth Street, and Gibson, Dunn & Crutcher LLP advised HealthCare Royalty.