Sionna cystic fibrosis drug fails key trial, removing threat to Vertex

Dive Brief:

An experimental cystic fibrosis drug from Sionna Therapeutics missed its main goal in a Phase 2 clinical trial, failing to show additive effects when layered on top of Vertex Pharmaceuticals’ popular medicine Trikafta, the company said Monday.
The closely watched trial compared a combination of Sionna’s SION-719 and Trikafta to Trikafta alone and evaluated their relative impact on “sweat chloride levels,” a sign of a drug’s potential effect on the disease. The regimen didn’t yield a statistically significant, placebo-adjusted change on that measure, badly missing a mark set by Sionna leadership.
Sionna’s shares fell nearly 92% in early trading Monday, leaving the company worth less than the $268 million in available cash and equivalents it had as of June 30. Company executives said they intend “to take actions to preserve capital while evaluating next steps.” Vertex shares, meanwhile, climbed by 7%.

Dive Insight:

Sionna is one of many companies that have faltered in challenging Vertex’s main business, a multi-drug franchise projected to bring in $13 billion in revenue this year. Like others before it, Sionna’s goal has been to improve upon Vertex’s pioneering therapies, which modulate a key protein that’s defective in cystic fibrosis and have proven to slow disease progression.

Sionna raised hundreds of millions of dollars in private and public funding to support the effort, amassing a portfolio of drugs designed to stabilize a particularly tricky region of that defective protein, “CFTR.” It licensed some prospects from AbbVie, too, hoping to develop its own combination regimens.

Sionna has claimed its drugs could help normalize function of the CFTR protein in ways Vertex’s medicines don’t. The Phase 2 trial reported Monday was a key test of that theory. It was testing whether Trikafta and a drug code-named SION-719 could help lower sweat chloride levels more effectively than Trikafta alone.

Going into the trial, Sionna executives had suggested that an improvement of “10 millimoles per liter” of sweat would be “clinically meaningful” and differentiate its drug. Sionna instead said Monday that that number was just 1 millimole per liter, a difference that wasn’t statistically significant.

In a client note following the company’s announcement, Stifel analyst Paul Matteis said the data are “hard to explain [and] leaves us puzzled.”

Others, like RBC Capital Markets’ Brian Abrahams, were skeptical beforehand. In a Monday note, Abrahams wrote that the “unfavorable setup” of Sionna having a high valuation going into the readout “played out,” and that all expectations have now been “washed out” of the company’s stock.

Sionna’s path forward will now depend on other medications, among them the drugs it acquired from AbbVie. In its announcement Monday, Sionna reported positive data from a Phase 1 trial testing one of those AbbVie drugs in combination with a therapy Sionna developed.

In a separate note on Vertex, Abrahams called the Sionna news a “clearing event” that makes him much more confident in recommending that investors buy shares.