Vertex Gives Update on Next-in-Class CF Therapy Amid Demand for Generics

Vertex_Craig F. Walker/The Boston Globe via Getty

Courtesy of Craig F. Walker/The Boston Globe via Getty

Amid growing demands for generic versions of Vertex’s Trikafta, the company provided an update on the late-stage clinical development of vanzacaftor/tezacaftor/deutivacaftor, its next-in-class triple combination treatment for cystic fibrosis.

The update was provided Tuesday in the company’s full-year 2022 financial results.

Concurrent with the financial report, patients living with CF, their families and other sympathetic groups launched a global campaign to challenge what they called the company’s monopoly on treatments.

The movement is led by patient-led organizations Vertex Save Us and Just Treatment.

Monday, the campaign filed a petition to the High Court of South Africa, seeking a compulsory license that, if granted, would allow for generic competition to Vertex’s Trikafta. Similar petitions were also filed the same day to the governments of Ukraine, India and Brazil.

First approved in 2019, Trikafta (elexacaftor/tezacaftor/ivacaftor) increases the quantity and function of the F508del-CFTR protein at the cell surface. Vertex has estimated the drug, and those like it, help approximately 90% of CF patients.

The next-in-class triple threat, vanzacaftor/tezacaftor/deutivacaftor, is designed to be taken once a day and also addresses the underlying causes of the disease.

In CF, the CFTR gene is mutated such that the protein it produces is incompletely processed and cannot be carried through the cell to be presented on its surface.

Vanzacaftor and tezacaftor assist in these processing and trafficking processes, thereby increasing the amount of the CFTR protein on the cell. Meanwhile, deutivacaftor is a potentiator that keeps CFTR engaged for much longer, leading to better clearance of mucus from the airways and easing CF symptom burden.

Though Trikafta has set a high bar in CF, Vertex expects its vanzacaftor program to “deliver even greater benefit to patients,” said Reshma Kewalramani, M.D., CEO and president director, Vertex, in an investor call Tuesday.

“The vanzacaftor triple also has the benefit of once-daily oral dosing and a substantially reduced royalty burden relative to Trikafta,” Kewalramani said.

Vertex is studying its next-in-class drug in the pivotal SKYLINE 102 and SKYLINE 103 trials, enrollments for which have been completed. These studies are designed to compare the safety and efficacy of vanzacaftor/tezacaftor/deutivacaftor with Trikafta in CF patients aged 12 years or older. A parallel study, dubbed RIDGELINE, is also assessing the triple combination candidate in children 6 to 11 years of age.

The company expects to complete both SKYLINE studies by the end of the year.

Meanwhile, Vertex is developing VX-522, an mRNA-based CF candidate, with Moderna. VX-522 works by delivering a functional copy of the CFTR gene into lung cells and is designed to treat patients who completely lack the gene.

The FDA signed off on an Investigational New Drug application for VX-522 in December, and Vertex began a single ascending dose study for the therapy, which it hopes to complete in 2023.

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