AstraZeneca $AZN reported Thursday that its drug Wainua failed to meet the primary goal of a late-stage clinical trial for a rare heart condition, sending the company's stock down as much as 9.9% in London trading and erasing roughly $27 billion in market value.
The Phase III CARDIO-TTRansform trial tested Wainua, a once-monthly gene silencer developed with Ionis Pharmaceuticals, in patients with transthyretin-mediated amyloid cardiomyopathy — a condition in which misfolded proteins accumulate in the heart muscle, making it harder to pump blood. Over the 140-week study period, adding Wainua to patients' existing care regimens failed to deliver a statistically significant improvement in cardiovascular mortality or recurring heart-related events relative to placebo, AstraZeneca said.
Shares of Ionis Pharmaceuticals fell as much as 15% in premarket trading. Shares of Alnylam $ALNY Pharmaceuticals, which already has a competing treatment for the condition on the market, rose 16% in premarket trading.
One key factor that complicated the trial's outcome was how many enrolled patients were already being treated with a stabilizer drug designed to stop the protein from misfolding. That prior treatment appears to have blunted Wainua's measurable impact, since layering a gene silencer onto an already-active therapy left little room to demonstrate additional benefit, according to CNBC. Among the subset of participants who had not been receiving stabilizer therapy when they enrolled, the data pointed to a nominally significant drop in mortality and cardiac events versus placebo, AstraZeneca noted.
The negative readout leaves intact Wainua's regulatory approval in a separate indication — a nerve-damaging disease driven by the same protein misfolding process. Complete trial results are scheduled to be shared at the European Society of Cardiology meeting this August.
"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," AstraZeneca Executive Vice President of BioPharmaceuticals R&D Sharon Barr said in a statement.
The result is a setback for AstraZeneca's ambitions beyond its core oncology business. The trial's failure follows a separate challenge the company faced earlier this year, when an FDA advisory panel voted against recommending approval of its experimental breast cancer drug camizestrant, citing concerns about the trial design and whether the drug showed a meaningful benefit.
Jefferies analyst Michael Leuchten told clients the miss leaves AstraZeneca's 2030 goal of $80 billion in revenue intact but raised questions about how confidently management had previewed the trial's prospects in the lead-up to Thursday's announcement, according to Bloomberg. "The bigger issue is probably a degree of credibility loss," Leuchten wrote in a note.