Today, BioPharma Dive is highlighting some notable clinical trial updates presented at the annual meeting of the European Society of Cardiology. Over the weekend, several large pharmaceutical and biotechnology companies released detailed study data on medicines for an array of different heart conditions.

Below are three notable datasets and a look at how they’re being interpreted by investors and analysts.

Cytokinetics’ stock sell-off

Cytokinetics claimed one of the bigger clinical trial victories in biotech this year when, in June, it disclosed that its drug Myqorzo succeeded in a Phase 3 trial in people with the “non-obstructive” form of the heart condition hypertrophic cardiomyopathy. That study made Myqorzo the first drug of its kind to prove beneficial against both forms of the condition, and separated it from Bristol Myers Squibb’s market leading medicine Camzyos.

On Friday, detailed data from that study were published in The New England Journal of Medicine and presented at ESC. Multiple Wall Street analysts claimed those findings reinforced Myqorzo’s potential — despite the disclosure of a possible safety concern that sank Cytokinetics’ stock price.

According to the NEJM paper, patients randomized to receive Myqorzo had an average 11.4-point improvement on a questionnaire assessing heart health after 36 weeks, compared to an 8.4-point change for placebo recipients. Peak oxygen consumption also improved for those treated with Myqorzo and slightly declined for those in the placebo group.

Overall, Myqorzo’s effects were “consistent” across all study groups analyzed, “reiterating” Cytokinetics’ initial results, wrote Leerink Partners analyst Roanna Ruiz. And, importantly, the drug’s impact on assessment scores appeared to grow over time, added Stifel’s James Condulis.

“The efficacy data are robust,” Condulis wrote in his own note.

Still, Cytokinetics shares fell more than 7% on Friday, as the paper also revealed 10 patients receiving Myqorzo experienced a specific kind of heart failure, versus three patients on placebo. That disclosure will likely add to an already “lingering debate” about the safety of Myqorzo and other drugs like it for people with non-obstructive disease, according to Condulis. (About one-third of patients have this form of HCM, which doesn’t impede blood flow to the heart but can still put people at risk of poor health outcomes.)

Yet Condulis and others argued the overall evidence should still support a new approval for Myqorzo and lead to broader uptake. Mizuho Securities analyst Salim Syed, for example, noted how there were no deaths among Myqorzo-treated patients, compared to three in the placebo arm. And patients with that form of the condition have “essentially zero options currently.”

The stock sell-off is “like missing [the] forest for trees,” Syed added.

Arrowhead’s edge

Arrowhead Pharmaceuticals and Ionis Pharmaceuticals are already dueling for market supremacy in a rare disease that leads to extremely high triglycerides. That battle is soon to extend to a more common condition, with potentially billions of dollars at stake — and where some analysts believe Arrowhead might have an advantage.

Arrowhead in July said its drug plozasiran met the objectives of two late-stage studies in adults with severe hypertriglyceridemia, or sHTG. Those findings positioned Arrowhead to expand plozasiran’s use and directly challenge Ionis, which nabbed an approval in sHTG for its drug Tryngolza in June.

At ESC, Arrowhead provided fuller details from those two studies and, to multiple analysts, described a drug with comparable efficacy to Tryngolza but potentially better safety. Prakhar Agrawal, of Cantor Fitzgerald, argued that plozasiran appears safer “across several metrics,” among them side effects leading to study discontinuations and liver enzyme or fat increases — the latter of which has been a key focus for investors.

The two drugs haven’t been tested against one another. But among patients who underwent a specialized imaging test in Arrowhead’s trials, plozasiran recipients had a roughly 1.5% placebo-adjusted increase in liver fat, compared to a 2% or 4% increase for Tryngolza recipients in Ionis’ studies, Agrawal noted.

While specialists Agrawal spoke with suggested the liver fat increases Ionis reported “may not be clinically meaningful,” his team nonetheless expects it to be a factor in Arrowhead’s drug becoming the preferred option.

Plozasiran’s results “arguably support a best-in-class profile,” wrote Condulis, from Stifel, in a separate note.

Arrowhead intends to file for approval by the end of the year, setting up a potential launch in 2027. Agrawal expects plozasiran to claim 60% of a market opportunity that could reach $6 billion by 2035.

A heart drug autopsy

In July, AstraZeneca and Ionis stunned industry watchers when they revealed eplontersen, a medicine they’ve been developing, missed the central objective of a Phase 3 study in transthyretin amyloidosis-mediated cardiomyopathy, a progressive and deadly heart condition. At ESC, study investigators presented a detailed autopsy of those results, and Wall Street analysts began assessing the fallout for others with rival medicines.

Alnylam already markets one drug called Amvuttra that, like eplontersen, interferes with the production of a protein implicated in the condition. It also has another, next-generation medication known as nucresiran that’s in late-stage testing. Eplontersen’s failure raised doubts about Amvuttra’s impact on the disease, and heightened skepticism about nucresiran’s chances of success.

William Blair analyst Myles Minter noted how AstraZeneca and Ionis’ findings call into question the benefits of combination therapy in TTR cardiomyopathy, where these “silencer” drugs might be used alongside the protein “stabilizers” patients typically receive. The results also fuel debate around the positioning of available therapies, which include Amvuttra and two branded stabilizers, Pfizer’s Vyndamax and BridgeBio Pharma’s Attruby, according to Minter.

In a separate note, Mizuho’s Syed wrote that AstraZeneca and Ionis’ data “increases [the] gap” between stabilizers and silencers and effectively boosted the case for Attruby. In the placebo group in the failed eplontersen trial, a majority of the patients were on Vyndamax and the level of protein stabilization observed was well short of what was seen in testing of Attruby. Syed argued that the results show “why a practitioner would choose Attruby” over Vyndamax — which will lose market exclusivity in 2031 — and suggests investors may be “modeling Attruby too conservatively” once generics are available, he wrote.

Analysts at Oppenheimer, meanwhile, rallied to Alnylam’s defense, noting that new analyses the company presented Sunday suggest Amvuttra may be more potent than eplontersen and that nucresiran might perform even better in Phase 3 testing. The reason, Oppenheimer’s Kostas Biliouris contended, is “modality differences” between Alnylam and Ionis’ drugs. Both medicines use different approaches — RNA interference for Alnylam’s drugs and antisense oligonucleotide therapy for Ionis’ — to achieve their intended effects.