Shares of Sionna Therapeutics dropped sharply Monday morning after the company announced its cystic fibrosis drug candidate failed a Phase 2a clinical trial as an add-on to Vertex Pharmaceuticals’ Trikafta. The PreciSION trial, which evaluated the nucleotide binding domain 1 stabilizer SION-719 in combination with Trikafta, did not meet its proof-of-concept goals, according to an Aug. 10 announcement from Sionna.
The company said it would discontinue development of SION-719 following the results. In pre-market trading, Sionna’s stock fell more than 90%. In the 15-patient study, SION-719 showed a -1.0mmol/L change in sweat chloride levels—a biomarker for cystic fibrosis—which was not statistically significant and well below the targeted reduction of 10mmol/L for patients already on Trikafta.
“We are disappointed in the unexpected results from the Phase 2a trial,” said Mike Cloonan, CEO of Sionna Therapeutics. Last week during a second-quarter earnings call, Cloonan described the PreciSION trial as validation for using NBD1 stabilizers to treat cystic fibrosis.
Analysts at BMO Capital Markets said that while this outcome is disappointing for Sionna, it may benefit Vertex by reinforcing “durability of Vertex’s CF franchise.” Shares of Vertex rose by 6% as of Monday morning. BMO analysts wrote, “Removal of Sionna as key competitor represents a meaningful positive for Vertex, reaffirming the company’s dominance in cystic fibrosis,” and added that failure of SION-719 removes a major obstacle for investors considering future growth prospects for Vertex’s key products Alyftrek and Trikafta.
Truist Securities analysts also commented that Vertex stands to gain from this result and that failure to show any improvement in sweat chloride levels highlights “the difficulty of demonstrating incremental benefit on top of Vertex’s highly effective CFTR modulators.” Stifel analysts expressed surprise at what they called “the unequivocal failure” and suggested that potential competitors will face challenges similar to those encountered by Sionna.
Sionna identified possible confounding factors such as variability in individual sweat chloride measurements and differences in exposure levels to Trikafta but acknowledged these remain under evaluation. The company plans to continue developing its earlier-stage candidates—SION-451 combined with another investigational drug called SION-2222—in an ongoing Phase 1 trial where no serious adverse events were reported.
