FDA Approves Expanded Use for Trikafta in Cystic Fibrosis

FDA officials approved an expanded use for elexacaftor/tezacaftor/ivacaftor and ivacaftor (Trikafta; Vertex Pharmaceuticals Inc) for the treatment of individuals with cystic fibrosis ages 2 and older who have at least 1 F508del mutation in the cystic fibrosis transmembrane conductance regulator (CFTR) gene or a mutation responsive to Trikafta based on clinical or in vitro data. This indication includes approximately 300 more patients with cystic fibrosis in the US.¹

3d illustration of cystic fibrosis | Image credit: Sebastian Kaulitzki | stock.adobe.com

Cystic fibrosis is caused by a defective and/or missing CFTR protein resulting from mutations in the CFTR gene. Although there are many types of CFTR mutations that can cause cystic fibrosis, most patients have at least 1 F508del mutation.^1,2

The defective function and/or absence of the CFTR protein causes poor flow of salt and water into and out of cells in multiple organs. In the lungs, this leads to the buildup of abnormally thick mucus, chronic lung infections, and progressive damage that eventually leads to death for many patients. The median age of death is in the 30s, but projected survival is improving with new treatments.²

Trikafta is an oral medication designed to increase the quantity and function of the CFTR protein at the cell surface. Elexacaftor and tezacaftor increase the amount of mature protein at the cell surface, while ivacaftor facilitates the ability of CFTR proteins to transport salt and water across the cell memberane. Together, these drugs hydrate and clear mucus from the airways.¹

“Since its first approval in 2019, Trikafta has had a transformative impact on tens of thousands of people living with cystic fibrosis,” Carmen Bozic, MD, executive vice president of Global Medicines Development and Medical Affairs and Chief Medical Officer at Vertex, said in a news release. “With this approval, even more patients may be able to benefit from a medicine that treats the underlying cause of their disease, and we look forward to continuing to work to extend the approvals and availability of our medicines to patients around the world.”¹

The efficacy of Trikafta prior to its initial approval was demonstrated in 2 clinical trials, each of which examined increases in the percent predicted forced expiratory volume in 1 second (ppFEV1), which is a marker of cystic fibrosis lung disease progression. In the first trial, treatment with Trikafta increased the ppFEV1 by 13.8% from baseline compared with placebo, and also resulted in improvements in sweat chloride, number of pulmonary exacerbations, and body mass index. In the second trial, it increased mean ppFEV1 10% from baseline compared with tezacaftor/ivacaftor.³

The safety profile is based on data from the 510 cystic fibrosis patients in the 2 trials and was generally similar across all subgroups. Serious adverse reactions that occurred more frequently in patients receiving Trikafta were rash and influenza. The most common adverse drug reactions included headaches, upper respiratory tract infections, abdominal pains, diarrhea, rashes, increased liver enzymes, nasal congestion, increased blood creatine phosphokinase, rhinorrhea, rhinitis, influenza, sinusitis, and increased blood bilirubin.³

In addition to this approval, the company also received an additional approval for vanzacaftor/tezacaftor/deutivacaftor (Alyftek) as a treatment of cystic fibrosis in people 6 years and older who have at least 1 F508del mutation or another CFTR gene mutation that is susceptible to the drug.

The approval was based on data from a comprehensive phase 3 pivotal program, with one study meeting it's primary end point of non-inferiority on absolute change from baseline in ppFEV₁ compared to Trikafta and all key secondary endpoints, including absolute change from baseline in sweat chloride [SwCl] compared to Trikafta.

“In phase 3 clinical trials, across a broad range of genotypes, once-daily Alyftek demonstrated non-inferiority to Trikafta in ppFEV₁ response and statistically significant improvement in SwCl, a welcomed advancement for the treatment of CF,” Claire L. Keating, MD, co-director of the Gunnar Esiason Adult Cystic Fibrosis and Lung Program at Columbia University, said in a news release. “Alyftek has the potential to improve the care of patients with CF.”

REFERENCES

1. Vertex Announces US FDA Approval for Trikafta (elexacaftor/tezacaftor/ivacaftor and ivacaftor) to Include Additional Non-F508del Trikafta-Responsive Variants. News release. Vertex Pharmaceuticals Inc. December 20, 2024. Accessed December 20, 2024. https://www.businesswire.com/news/home/20241220045992/en/Vertex-Announces-U.S.-FDA-Approval-for-TRIKAFTA-elexacaftortezacaftorivacaftor-and-ivacaftor-to-Include-Additional-Non-F508del-TRIKAFTA-Responsive-Variants

2. Cystic Fibrosis. National Heart, Lung, and Blood Institute. Updated November 15, 2024. Accessed December 20, 2024. https://www.nhlbi.nih.gov/health/cystic-fibrosis/causes

3. FDA approves new breakthrough therapy for cystic fibrosis. News release. FDA. October 21, 2019. Accessed December 20, 2024. https://www.fda.gov/news-events/press-announcements/fda-approves-new-breakthrough-therapy-cystic-fibrosis

4. Vertex Announces US FDA Approval of ALYFTREK, a Once-Daily Next-in-Class CFTR Modulator for the Treatment of Cystic Fibrosis. News release. Vertex Pharmaceuticals. December 20, 2024. Accessed December 20, 2024. https://www.businesswire.com/news/home/20241220133127/en/Vertex-Announces-US-FDA-Approval-of-ALYFTREK%E2%84%A2-a-Once-Daily-Next-in-Class-CFTR-Modulator-for-the-Treatment-of-Cystic-Fibrosis