Acoramidis

iStock, Matthew Malczewski The failure of AstraZeneca and Ionis’ Wainua in a late-stage study of ATTR-CM casts doubt on Alnylam’s next-generation candidate but is good news for others in the space, including BridgeBio and Intellia Therapeutics. The surprising late-stage failure of AstraZeneca and Ionis’ antisense oligonucleotide Wainua in transthyretin amyloidosis cardiomyopathy this week has shaken the field, sowing doubt in certain therapies while building investor confidence in others. “The study here was expected to work since we know TTR [transthyretin] silencers are effective,” Stifel told investors in a Thursday note, referring to Wainua’s mechanism of suppressing the expression of the TTR protein, which is misfolded in ATTR-CM, leading to pathologic clumps in the heart. “This is absolutely the most complicated possible outcome” for Alnylam, Stifel analysts wrote, referring to the biotech’s FDA-approved Amvuttra that’s indicated for both hereditary ATTR-CM and polyneuropathy in transthyretin amyloidosis (ATTR). Alnylam is also advancing its RNAi candidate nucresiran for these conditions. Both programs work similarly to Wainua by silencing TTR. AstraZeneca and Ionis’ setback on Thursday “represents a near-term ‘win’ for ALNY by leaving Amvuttra as the only approved TTR silencer for ATTR-CM,” Truist Securities explained in a Thursday note. But the failure “raises questions about outlook for ALNY’s next-generation silencer, nucresiran, and its ability to demonstrate incremental clinical benefit in a treatment landscape increasingly dominated by background stabilizer therapy.” Earnings ‘Very Impressive’ Amvuttra ATTR-CM Sales Send Alnylam Soaring In its first commercial quarter for ATTR-cardiomyopathy, Alnylam’s Amvuttra reached roughly 1,400 patients and made more than $490 million. August 1, 2025 · 2 min read · Tristan Manalac Read more Alnylam is studying nucresiran in the Phase 3 TRITON-CM study , which is currently recruiting patients and expected to readout in 2030. The biotech “remains very confident” in nucresiran and TRITON, Oppenheimer wrote Thursday after a Q&A session with the company. In particular, the firm pointed to three key advantages emphasized by Alnylam: nucresiran is a better molecule than Wainua in potency, durability and onset; TRITON-CM is a larger trial than AstraZeneca and Ionis’ study; and Alnylam has a leadership team with proven experience. “We remain positive on ALNY ahead of TRITON,” Oppenheimer said. Alnylam ended Thursday’s trading session down 3.3%, while BridgeBio, on the other hand, swelled 15%. Tailwind for some AstraZeneca and Ionis’ failure “simplifies the ATTR-CM landscape,” Mizuho Securities wrote in a Thursday note focused on BridgeBio. The biotech owns the TTR stabilizer Attruby, approved in November 2024 for ATTR-CM. Unlike Wainua and Amvuttra, which reduce the expression of TTR, Attruby instead binds to the protein and prevents a crucial step in the formation of the disease-causing clumps. Earlier this month, BridgeBio presented a post-hoc analysis of Phase 2 and Phase 3 data for Attruby, pointing to the drug’s potential to preserve kidney function in ATTR-CM—a key renal benefit that could set it apart from other therapies in this space. Another drug that works similarly to Attruby is Pfizer’s Vyndaqel/Vyndamax, which was approved in 2019 and made $1.7 billion worldwide last year. But Phase 3 data in May suggest that Attruby has a survival edge in ATTR-CM. Cardiovascular disease BridgeBio stands up to Pfizer in ATTR-CM as late-stage data hint at better survival Indirect comparisons between BridgeBio’s Attruby and Pfizer’s tafamidis products showed a numerical survival benefit with the biotech’s drug. May 12, 2026 · 2 min read · Tristan Manalac Read more There has been no direct head-to-head comparison between the two medicines, but Mizuho nevertheless noted that Attruby is a better option in the hospital. “Because ATTR-CM is still a fatal disease, physicians should opt for the more potent stabilizer, BBIO’s Attruby.” “Peak sales estimates for Attruby may edge higher” with Wainua out of the picture, the group added. The drug brought in $362.4 million in 2025. Also in the ATTR-CM arena is Intellia Therapeutics, a biotech advancing the CRISPR-based gene therapy nexiguran ziclumeran (nex-z). Two Phase 3 studies of nex-z were subject to an FDA hold last October after a patient in one of the trials developed life-threatening liver enzyme elevations. The agency has since fully lifted the pause. Nex-z works by deactivating the TTR gene and reducing the overall expression of the protein—much like Wainua and other silencer therapies. What sets Intellia’s candidate apart, however, is that it’s designed to be a one-time therapy. The biotech is advancing nex-z in collaboration with Regeneron. The Wainua fail delivers an incremental positive to nex-z, Jefferies wrote in a Thursday note, reinforcing the analysts’ view “that achieving deep+consistent TTR knockdown is needed to drive benefit on outcomes.” “Beyond stabilizer progression, we still expect ATTR [patients] to look for the next best option,” the analysts said.

iStock, Phira Phonruewiangphing BridgeBio’s Attruby preserves kidney function in patients with transthyretin amyloidosis cardiomyopathy, an effect that is “distinct” from other drugs in this space, according to Jefferies. BridgeBio’s protein stabilizing therapy Attruby appears to protect kidney function in patients with transthyretin amyloidosis cardiomyopathy—a key clinical benefit that analysts say could help the drug stand out in a crowded market for this indication. The findings come from a posthoc analysis released Thursday that drew data from a Phase 2 study of Attruby, as well as the Phase 3 ATTRibute-CM trial, results from which led to the drug’s approval in November 2024 . The posthoc evaluation found that patients on Attruby saw an initial but reversible decrease in estimated glomerular filtration rate (eGFR), a common measure used to quantify kidney function, with decreasing values suggesting worse filtering. At 30 months of follow-up, however, the slope of eGFR changes showed sustained and significant placebo-adjusted improvements, according to BridgeBio, suggesting “direct kidney-protective effects” in patients. “The acute dip in eGFR following initiation of [Attruby] may represent a beneficial kidney effect,” the biotech said on Thursday. Alongside these eGFR changes, BridgeBio documented significant and sustained reductions in urinary albumin-to-creatinine ratio, an indicator of kidney damage, though 30 months. Jefferies was positive on the news, telling investors in a Thursday note that the posthoc assessments “point to cardiorenal protective benefits” for Attruby. “The degree of kidney function protection”—as measured by the positive changes in eGFR slope—“looks competitive to kidney-targeted therapies,” the analysts added. “Ultimately, slowing down kidney progression could improve hospitalization/mortality outcomes.” More broadly, the posthoc analysis “adds differentiation” to Attruby in transthyretin amyloidosis cardiomyopathy (ATTR-CM), Jefferies said, noting that the “cardiorenal protective effects seem distinct from other therapies” in this space. In particular, the firm pointed to Pfizer’s Vyndaqel/Vyndamax , which was approved in 2019 and last year grew 16% to $6.4 billion in worldwide sales . Also looking to compete in ATTR-CM are AstraZeneca and Ionis, which are testing their antisense oligonucleotide Wainua, currently approved to treat polyneuropathy caused by hereditary transthyretin-mediated amyloidosis (hATTR-PN), for a possible expansion into ATTR-CM. The partners are expected to release Phase 3 data for the asset in late August, Jefferies said Thursday. For BridgeBio, the posthoc data come after a late-stage win in achondroplasia last week. The company’s oral drug infigratinib not only boosted growth in children but also significantly improved body proportionality. As in the case of Attruby, analysts see this achondroplasia outcome as a key differentiator for BridgeBio in the space. “Other players do not seem to hit stat-sig” in body proportionality, Jefferies told investors in a June 28 note. “We think proportionality drives meaningful outcomes in daily activities and mobility,” the analysts wrote. “We are optimistic proportionality will be included in the label.” Rare diseases BridgeBio’s achondroplasia pill shows ‘compelling’ growth and body proportionality benefit BridgeBio Pharma plans to approval in the third quarter. If granted, the oral drug could present a “highly differentiated” option over current achondroplasia therapies, according to Jefferies. June 29, 2026 · 2 min read · Tristan Manalac Read more