After pausing a trial for a Moderna-partnered cystic fibrosis candidate due to subpar tolerability, Vertex Pharmaceuticals has now decided to discontinue the program entirely.
Vertex initially paused a phase 1/2 trial of VX-522, an inhaled mRNA therapy for CF, last May to “assess a tolerability issue.” That issue has now become “persistent,” Vertex announced in its quarterly earnings today, leading the pharma to end the study and terminate development entirely.
“Despite actions we have taken in the trial to overcome these issues, we have not been able to do so, and as such, we have chosen to discontinue the program,” Vertex CEO Reshma Kewalramani, M.D., said during the company’s earnings call. “Given this early termination, we will not be able to assess the efficacy or full safety of VX-522. We will be working with sites to close out the study in the coming weeks.”
The issue was lung inflammation, Kewalramani said during the call, likely caused by the lipid nanoparticle used to deliver the candidate.
“This 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,” Moderna CEO Stéphane Bancel said in a May 4 blog post. “Despite extensive efforts by both teams, we were not able to achieve a profile that supported continued development given tolerability issues.”
Given how fresh the decision is, “it will take us some time to work with the Moderna team to determine next steps,” a Vertex spokesperson told Fierce Biotech.
Vertex and Moderna kicked off the partnership that spawned VX-522 (also called mRNA-3692) back in 2016, with Moderna netting $20 million upfront in a deal potentially worth as much as $300 million. The pair deepened their bond in 2020 with a new three-year pact that saw Vertex pay Moderna $75 million to work on mRNA-based gene therapies for CF.
VX-522 was the first program in Moderna’s inhaled pulmonary therapeutics modality, according to a 2023 presentation from the company, and was never joined by any other candidates.
“This program represented our only inhaled therapeutic approach and utilized a unique formulation and delivery system, with no broader implications for our portfolio,” Bancel wrote in his blog post. “That said, the learnings are important and will inform our broader scientific efforts as we continue to advance our mRNA pipeline across multiple modalities.”
VX-522 was meant to deliver mRNA coding for the cystic fibrosis transmembrane conductance regulator (CFTR) protein, which is defective or missing entirely in CF. Vertex built its business on drugs that enhance CFTR’s function, but as many as 10% of CF patients don’t have any of the protein and thus can’t benefit from existing treatments.
Despite the loss of VX-522, Vertex remains committed to creating medicines for all CF patients, Kewalramani said on the call, including those that have no functional CFTR protein.
“Our commitment to CF is absolute and steadfast,” Kewalramani said. “I expect that the challenge is going to continue to be delivery, and in terms of modalities, we're going to have to go back to the drawing board.”