Safety concerns lead to early stop of trial testing inhaled CF treatment
Vertex ends VX-522 development, but says it's advancing other therapies
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An early clinical trial testing inhaled cystic fibrosis (CF) treatment VX-522 — being developed for adults with CF who are not eligible for certain available therapies — has been terminated before its completion due to “persistent tolerability issues,” according to an update from Vertex Pharmaceuticals.
Vertex, which was codeveloping VX-522 with Moderna, said that the early stop to the Phase 1/2 BEACON-CF study (NCT05668741) means that full analyses of the experimental therapy’s safety and effectiveness will not be possible.
Thus, the trial’s early termination “prevents further development of the VX-522 program,” Vertex stated in a company press release reporting first-quarter financial results.
The company noted, however, that it is actively developing several other potential CF treatments that are now in clinical trials. These include VX-828.
In a blog post on Moderna‘s part, CEO Stéphane Bancel wrote that “despite extensive efforts by both teams, we were not able to achieve a profile that supported continued development given tolerability issues.”
A genetic condition, CF is caused by mutations in the gene that encodes the protein CFTR, which helps balance salt and water on body surfaces. Lacking functional CFTR protein, people with CF produce unusually thick and sticky mucus, which builds up in the body’s organs to drive most disease symptoms.
VX-522 was an RNA-based therapy designed to restore CFTR protein production in lung cells. The trial had enrolled an estimated 39 people with CF who were not responsive to other CFTR modulator therapies.
Bancel, in the blog post, wrote that the program’s termination “is a disappointing outcome, particularly for patients and families in the CF community who continue to wait for new options, and for the many colleagues across Vertex and Moderna who have dedicated years to this program.” The CEO extended his personal thanks to all the researchers, staff, and patients who participated in the therapy’s development.
Vertex now testing other CF treatments in trials
Vertex is the maker of several CFTR modulators, which are medications that can increase the activity of the defective CFTR protein in people with certain mutations. The company’s first-generation triple-combination modulator therapy, Trikafta (elexacaftor/tezacaftor/ivacaftor; sold as Kaftrio in Europe), is widely approved to treat CF patients with eligible mutations. A second-generation triple-combo modulator, called Alyftrek (vanzacaftor/tezacaftor/deutivacaftor), was approved in the U.S. in 2024 for eligible patients ages 6 and older.
In its financial updates, Vertex said that its total revenue in the first quarter of this year was nearly $3 billion, driven mainly by sales of these two CF medications. The company said it expects to earn more than $13 billion in revenue over the course of this year.
Trikafta and Alyftrek have revolutionized care for most CF patients. Still, Vertex said it is not stopping with these available treatments. Indeed, the company is already developing three third-generation modulator therapies: VX-581 and VX-272, as well as VX-828.
A Phase 1 study (NCT06154447) sponsored by Vertex is now testing VX-828, both on its own and in combination with tezacaftor and deutivacaftor (two of the modulators in Alyftrek). The trial is enrolling people with CF and healthy controls, with the main goals of evaluating VX-828’s safety and pharmacological profile. Recruitment is ongoing at a dozen sites across the U.S. Vertex said it is on track to finish dosing in the next month or two, with results expected later this year.
Vertex is also running Phase 1 studies testing VX-581 (NCT07283770) or VX-272 (NCT07437105) in healthy volunteers, with the main goal of assessing the safety and pharmacological profiles of these therapies.
