Shares of AstraZeneca fell as much as 9% after a late-stage clinical trial for a heart disease drug failed to meet its target, with analysts saying the bigger issue may be investors’ trust in the company rather than the loss of a few extra billion in sales.
Wainua – a medicine AstraZeneca had been testing on whether it could help patients with a rare heart condition – did not reach its main goal of reducing deaths and recurrent heart-related emergencies over 140 weeks compared to a placebo, the British drugmaker said in a press release early Thursday.
It examined how the medicine could help patients with a rare, life-threatening heart condition called transthyretin-mediated amyloid cardiomyopathy, or ATTR cardiomyopathy, when added to a patient’s current treatment plan
Jefferies analysts said the result didn’t jeopardise the company’s $80 billion sales target by 2030 but noted that AstraZeneca “had been very confident around the primary endpoint and the ability to hit in combination use.”
“The bigger issue is probably a degree of credibility loss with management being very confident in the trial’s ability to hit the primary endpoint as well as an ability to show utility on top of background therapy,” the analysts said, modeling for $2.5 billion less in risk-adjusted sales for the medicine.
Under CEO Pascal Soriot’s leadership over the past 14 years, AstraZeneca has developed a reputation as a steadfast powerhouse, especially in oncology. It rarely posts negative trial results, and Thursday’s surprise disappointment may have ripple effects beyond the medicine itself.
A rare miss
AstraZeneca confirmed that its existing license for Wainua was unaffected by these trial results. The drug is already approved for treating conditions where misfolded proteins build up, causing nerve damage. It is sold in Europe as Wainzua.
This study examined a specific type of the condition in which misfolded proteins accumulate in the heart muscle, stiffening it and making it difficult to pump blood, and eventually leading to heart failure. It’s estimated that about half a million people live with the condition.
AstraZeneca’s London-listed shares over the past 12 months.
The stock was last seen down 8.7% in London, on track for its worst day since March 2020 at the start of the Covid-19 outbreak.
It weighed heavily on the U.K’s bluechip index FTSE 100, which shed 0.5%, making it the only major European index in the red on Thursday.
AstraZeneca’s NYSE-listed shares were down 8.4% in morning trading. Shares of Ionis Pharmaceuticals, which is co-developing Wainua in the U.S., plummeted 19%.
AstraZeneca and Ionis’ failure removes one player in the increasingly competitive ATTR cardiomyopathy market.
For years, Pfizer’s Vyndamax was the only drug approved for the condition. That changed in recent years with BridgeBio introducing a new pill that stabilizes the transthyretin protein, similar to how Pfizer’s drug works, and Alnylam introducing a drug that silences the production of transthyretin, a similar approach that AstraZeneca and Ionis were pursuing.
Wainua’s failure means that Alnylam’s drug Amvuttra will be the only silencer, giving it a monopoly in the market for ATTR cardiomyopathy silencing drugs, Oppenheimer analyst Kostas Biliouris wrote in a note Thursday.
Amvuttra will likely also dominate in ATTR polyneuropathy, when misfolded proteins deposit in nerves, because it’s now the only silencer proven to benefit both manifestations of the condition. Biliouris estimates the entire market for ATTR cardiomyopathy to be between $15 billion to $20 billion but said it’s hard to know for sure since although it was once thought to be rare, it’s turning out to be more common.
Shares of Alnylam rose about 15% in morning trading, while shares of BridgeBio rose 13%.
No added benefit
In AstraZeneca’s study cohort, a majority of patients were already on a stabilizer that keeps the protein from misfolding in the first place. Because patients were already receiving treatment for this, adding Wainua on top of standard of care didn’t show a significant extra benefit to the overall group.
For patients not taking a stabilizer at baseline, Wainua showed a “nominally significant” risk reduction in deaths and heart events compared to placebo, AstraZeneca said.
AstraZeneca is meant to be able to have “exceptionally good trial design ability,” and to see the trial fail on design flaws like the percentage of patients on stabilizers, will hit the company’s credibility, Jefferies said.
AstraZeneca said that 57% of patients received a stabilizer treatment at baseline, and a further 24% initiated a stabilizer during the trial.
“We would not be surprised seeing people pause for now until the catalyst path is clearer,” Jefferies said, noting that the stock may not recover until the next big event for the stock – the AVANZAR trial for lung cancer – is out of the way.
Citi analysts said it was unlikely AstraZeneca could file for additional approvals for Wainua given the primary endpoint miss, as Alnylam‘s Amvuttra is already on the market.
“Although the trial did not meet its primary objective, we believe the results support greater scientific understanding of treatment approaches for the hundreds of thousands of patients worldwide suffering from this progressive and often fatal condition,” said AstraZeneca Executive Vice President of BioPharmaceuticals R&D Sharon Barr.
Full data will be presented at the European Society of Cardiology in August.
Correction: This story has been updated to correct Oppenheimer’s market size estimate for ATTR cardiomyopathy. The analyst estimates the market to be between $15 billion and $20 billion.
