More CF patients eligible for Alyftrek, Trikafta after new FDA decision
Expanded labels include additional CFTR mutations
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The U.S. Food and Drug Administration (FDA) has expanded the approvals of two Vertex Pharmaceuticals therapies to include additional mutations that cause cystic fibrosis (CF), allowing more people with the condition to become eligible for treatment.
The decision concerns Alyftrek (vanzacaftor/tezacaftor/deutivacaftor) and Trikafta (elexacaftor/tezacaftor/ivacaftor). These are CFTR modulators that help improve the function of the CFTR protein, which is impaired in CF due to mutations in the CFTR gene.
Expanded labels include additional CFTR mutations
With the new expansions, the two medications are now indicated for people with at least one CFTR mutation that has been shown to be responsive based on clinical and/or laboratory (in vitro) data, or that results in at least some production of the CFTR protein.
The label expansions were supported by clinical and laboratory data showing that 564 mutations responded to Alyftrek and 521 responded to Trikafta.
The decision makes 800 more people with CF in the U.S. eligible to receive therapies that target the underlying cause of their disease, according to Vertex, which estimates that approximately 95% of people with CF in the country may now have the option of a CFTR modulator.
“This groundbreaking approval represents more than 20 years of innovation in CF, including testing over 600 variants in our laboratory, demonstrating clinical effects in large clinical trials, and studying younger people with CF so they can be treated as early as possible,” Carmen Bozic, MD, executive vice president of global medicines development and medical affairs and chief medical officer at Vertex, said in a company press release.
CFTR mutations disrupt protein function in cystic fibrosis
In CF, certain mutations in the CFTR gene lead to a faulty or missing CFTR protein. This impairs the flow of salt and water into and out of the cells, resulting in the buildup of abnormally thick, sticky mucus in various organs. To date, more than 2,500 CFTR mutations have been identified.
CFTR modulators, such as Alyftrek and Trikafta, are designed to help improve the function of certain faulty versions of the CFTR protein. This can help the body produce thinner, more easily cleared mucus, which may ease symptoms and slow organ damage.
Each of the two therapies was previously approved in the U.S. to treat people with specific CF-causing mutations in the CFTR gene. The label expansions were supported by preclinical and clinical data showing that additional CFTR mutations are responsive to these therapies.
Under the updated label, Alyftrek is now approved for people with CF ages 6 and older who carry at least one F508del mutation — the most common CF-causing mutation — or another CFTR mutation that is responsive to treatment based on clinical and/or laboratory data, or that results in the production of the CFTR protein.
Updated approvals expand access to Alyftrek and Trikafta
Trikafta is similarly approved for people who carry at least one CFTR mutation that is responsive based on clinical and/or laboratory data or that results in the production of some CFTR protein. Its indication includes people with CF as young as 2.
“With this label expansion, any variant that results in production of CFTR protein is now included in the Alyftrek and Trikafta labels, validating that these medicines can restore CFTR function and provide clinical benefit to patients regardless of where in the CFTR protein a variant is located,” Bozic said.
“We thank the CF community and investigators for their trust and look forward to bringing Alyftrek and Trikafta to more patients than ever before,” Bozic added.
