A surprise flop in Phase 2a cystic fibrosis trial sent Sionna’s shares plummeting, but for Vertex, the news reinforced its standard-of-care standing with highly successful drugs like Trikafta.
Shares of Sionna Therapeutics tanked Monday morning on news that the company’s cystic fibrosis drug candidate failed a Phase 2a clinical trial as an add-on to Vertex Pharmaceuticals’ blockbuster Trikafta.
The PreciSION trial served as a proof-of-concept study for the drug candidate, a nucleotide binding domain 1 stabilizer called SION-719, to be used together with Trikafta, considered standard of care for patients with cystic fibrosis. But in its Monday announcement of the trial results, Sionna said it would discontinue development of SION-719.
Sionna’s stock fell more than 90% in pre-market trading.
In the15-patient trial, SION-719 showed a -1.0mmol/L change in sweat chloride levels, a biomarker for cystic fibrosis. The decrease was not statistically significant, falling far short of the goal to reduce levels by 10mmol/L in patients already taking Trikafta.
“We are disappointed in the unexpected results from the Phase 2a trial,” Sionna CEO Mike Cloonan said in a release. In a second-quarter earnings call last week, Cloonan pointed to the PreciSION trial as a validation of Sionna’s core belief in NBD1 stabilizers to treat cystic fibrosis.
But a disappointment for Sionna in this space is a potential advantage for Vertex, as the trial failure “reinforces durability of Vertex’s CF franchise,” according to analysts at BMO Capital Markets.
Shares of Vertex rose 6% as of 10 a.m. Monday.
“Removal of Sionna as key competitor represents a meaningful positive for Vertex, reaffirming the company’s dominance in cystic fibrosis,” BMO wrote. “Failure of SION-719 removes a key overhang for Vertex shares, allowing for investors to look to future continued growth of the company’s key CF products (e.g., Alyftrek and Trikafta) unfettered by meaningful competition in the near term.”
Truist Securities analysts agreed not only that Vertex stands to benefit from the failure but that Sionna’s failure to show any evidence of activity in sweat chloride levels “underscores the difficulty of demonstrating incremental benefit on top of Vertex’s highly effective CFTR modulators.” This, the analysts continued, “suggests the path to meaningfully improving upon Trikafta may be more challenging than preclinical models may imply.”
Sionna’s failed trial came as a shock to some analysts, including those from Stifel, who wrote: “We are disappointed, and very surprised, by the unequivocal failure of the ph2a readout,” adding that Sionna would likely be a “show-me story” for potential Vertex competitors.
Sionna pointed to some potential trial confounders, including variability in individual sweat chloride levels and differences in Trikafta exposure levels, according to a press release. But Stifel analysts pointed out that these are working theories still under evaluation.
Sionna will continue development of its earlier-stage cystic fibrosis candidate SION-451 combined with another potential drug called SION-2222 in a Phase 1 trial. The combination was well-tolerated in healthy participants with no serious adverse events and two discontinuations for an elevated liver function test and flu-like symptoms.
