Vertex Announces U.S. FDA Approval for TRIKAFTA (elexacaftor/tezacaftor/ivacaftor and ivacaftor) to Include Additional Non-F508del TRIKAFTA-Responsive Variants
VRTX 12.20.2024
About Gravity Analytica
- Approximately 300 more people with cystic fibrosis in the
“Since its first approval in 2019, TRIKAFTA has had a transformative impact on tens of thousands of people living with cystic fibrosis,” said
For more information on TRIKAFTA, patient assistance programs or to find additional eligibility details, visitTRIKAFTA.com,VertexGPS.comorvertextreatments.com.
About Cystic Fibrosis
Cystic fibrosis (CF) is a rare, life-shortening genetic disease affecting more than 92,000 people globally. CF is a progressive, multi-organ disease that affects the lungs, liver, pancreas, GI tract, sinuses, sweat glands and reproductive tract. CF is caused by a defective and/or missing CFTR protein resulting from certain mutations in theCFTRgene. Children must inherit two defectiveCFTRgenes — one from each parent — to have CF, and these mutations can be identified by a genetic test. While there are many different types ofCFTRmutations that can cause the disease, the vast majority of people with CF have at least oneF508delmutation.CFTRmutations lead to CF by causing CFTR protein to be defective or by leading to a shortage or absence of CFTR protein at the cell surface. The defective function and/or absence of CFTR protein results in poor flow of salt and water into and out of the cells in a number of organs. In the lungs, this leads to the buildup of abnormally thick, sticky mucus, chronic lung infections and progressive lung damage that eventually leads to death for many patients. The median age of death is in the 30s, but with treatment, projected survival is improving.
Today
About TRIKAFTA (elexacaftor/tezacaftor/ivacaftor and ivacaftor)
In people with certain types of mutations in theCFTRgene, the CFTR protein is not processed or folded normally within the cell, and this can prevent the CFTR protein from reaching the cell surface and functioning properly. TRIKAFTA (elexacaftor/tezacaftor/ivacaftor and ivacaftor) is an oral medicine designed to increase the quantity and function of the CFTR protein at the cell surface. Elexacaftor and tezacaftor work together to increase the amount of mature protein at the cell surface. Ivacaftor, which is known as a CFTR potentiator, is designed to facilitate the ability of CFTR proteins to transport salt and water across the cell membrane. The combined actions of elexacaftor, tezacaftor and ivacaftor help hydrate and clear mucus from the airways.
TRIKAFTA (elexacaftor/tezacaftor/ivacaftor and ivacaftor) is a prescription medicine used for the treatment of cystic fibrosis (CF) in patients aged 2 years and older who have at least one copy of theF508delmutation or a mutation in theCFTRgene that is responsive based on clinical and/orin vitrodata. Patients should talk to their doctor to learn if they have an indicated CF gene mutation. It is not known if TRIKAFTA is safe and effective in children under 2 years of age.
The following 94 mutations have been added to the TRIKAFTA®label for the first time:
1507_1515del9,2183A→G,A1067P,A107G,A309D,A62P,C491R,D1445N,D565G,D993Y,E116Q,E292K,F1107L,F200I,F587I,G1047R,G1123R,G1247R,G27E,G424S,G480S,G551A,G970S,H620P,H620Q,H939R;H949L,I105N,I125T,I148N,I331N,I506L,I556V,K162E,K464E,L1011S,L137P,L333F,L333H,L441P,L619S,M1137V,M150K,N1088D,N1303I,N186K,N187K,N418S,P140S,P499A,P750L,Q1313K,Q372H,Q493R,Q552P,R1048G,R117C;G576A;R668C,R297Q,R31C,R516S,R555G,R709Q,R75L,S1045Y,S108F,S1118F,S1235R,S549I,T1086I,T1246I,T1299I,T351I,V392G,V603F,Y301C,2789+5G→A,3272-26A→G,3849+10kbC→T,N1303K,711+3A→G,E831X,5T;TG12,5T;TG13,296+28A→G,621+3A→G,1898+3A→G,2789+ 2insA,3850-3T→G,3600G→A,3849+4A→G,3849+40A→G,4005+2T→C,1341G→A,3041-15T→G,2752-26A→G
TRIKAFTA
TRIKAFTA is indicated for the treatment of cystic fibrosis (CF) in patients aged 2 years and older who have at least one F508del mutation in the cystic fibrosis transmembrane conductance regulator (CFTR) gene or a mutation in the CFTR gene that is responsive based on clinical and/or in vitro data.
If the patient’s genotype is unknown, an FDA-cleared CF mutation test should be used to confirm the presence of at least one indicated mutation.
IMPORTANT SAFETY INFORMATION
BOXED WARNING: DRUG-INDUCED LIVER INJURY AND LIVER FAILURE
TRIKAFTA can cause serious and potentially fatal drug-induced liver injury. Cases of liver failure leading to transplantation and death have been reported in patients with and without a history of liver disease taking TRIKAFTA, in both clinical trials and the post-marketing setting. Liver injury has been reported within the first month of therapy and up to 15 months following initiation of TRIKAFTA.
Assess liver function tests (ALT, AST, alkaline phosphatase, and bilirubin) in all patients prior to initiating TRIKAFTA, then every month during the first 6 months of treatment, every 3 months for the next 12 months, and at least annually thereafter. Consider more frequent monitoring for patients with a history of liver disease or liver function test (LFT) elevations at baseline.
Interrupt TRIKAFTA for significant elevations in LFTs or in the event of signs or symptoms of liver injury. Consider referral to a hepatologist. Follow patients closely with clinical and laboratory monitoring until abnormalities resolve. If resolved, resume treatment only if the benefit is expected to outweigh the risk. Closer monitoring is advised after resuming TRIKAFTA.
TRIKAFTA should not be used in patients with severe hepatic impairment (Child-
WARNINGS AND PRECAUTIONS
Drug-Induced Liver Injury and Liver Failure
- TRIKAFTA can cause serious and potentially fatal drug-induced liver injury. Liver failure leading to transplantation and death have been reported in patients with and without a history of liver disease taking TRIKAFTA. Liver injury has been reported within the first month of therapy and up to 15 months following initiation of TRIKAFTA
- Assess LFTs (ALT, AST, alkaline phosphatase, and bilirubin) in all patients prior to initiating TRIKAFTA, then every month during the first 6 months of treatment, every 3 months for the next 12 months, at least annually thereafter
- Interrupt TRIKAFTA in the event of signs or symptoms of liver injury, which may include:
- Significant elevations in LFTs (e.g. ALT or AST >5x the upper limit of normal (ULN) or ALT or AST >3x ULN with bilirubin >2x ULN)
- Clinical symptoms suggestive of liver injury (e.g., jaundice, right upper quadrant pain, nausea, vomiting, altered mental status, ascites)
- Consider referral to a hepatologist and follow patients closely with clinical and laboratory monitoring until the abnormalities resolve. If resolved, and if benefit is expected to outweigh risk, resume TRIKAFTA with close monitoring
- TRIKAFTA should not be used in patients with severe hepatic impairment . TRIKAFTA is not recommended in patients with moderate hepatic impairment and should only be considered when there is a clear medical need, and benefit outweighs risk. If used, use with caution at a reduced dosageand monitor patients closely
Hypersensitivity Reactions, Including Anaphylaxis
- Hypersensitivity reactions, including cases of angioedema and anaphylaxis, have been reported in the post-marketing setting. If signs or symptoms of serious hypersensitivity reactions develop during treatment, discontinue TRIKAFTA and institute appropriate therapy. Consider benefits and risks for the individual patient to determine whether to resume treatment with TRIKAFTA
Concomitant Use With CYP3A Inducers
- Exposure to ivacaftor is significantly decreased and exposure to elexacaftor and tezacaftor are expected to decrease by concomitant use of strong CYP3A inducers, which may reduce the therapeutic effectiveness of TRIKAFTA. Concomitant use with strong CYP3A inducers is not recommended
Concomitant Use With CYP3A Inhibitors
- Exposure to elexacaftor, tezacaftor, and ivacaftor are increased when used concomitantly with strong or moderate CYP3A inhibitors. The dose of TRIKAFTA should be reduced when used concomitantly with moderate or strong CYP3A inhibitors
Cataracts
- Non-congenital lens opacities have been reported in pediatric patients treated with ivacaftor-containing regimens. Baseline and follow-up ophthalmological examinations are recommended in pediatric patients initiating treatment with TRIKAFTA
ADVERSE REACTIONS
Serious Adverse Reactions
- Serious adverse reactions that occurred more frequently in patients treated with TRIKAFTA compared to placebo were rash (1% vs <1%) and influenza (1% vs 0%)
Most Common Adverse Reactions
- The most common adverse reactions occurring in ≥5% of patients treated with TRIKAFTA and higher than placebo by ≥1% were headache, upper respiratory tract infection, abdominal pain, diarrhea, rash, alanine aminotransferase increased, nasal congestion, blood creatine phosphokinase increased, aspartate aminotransferase increased, rhinorrhea, rhinitis, influenza, sinusitis, and blood bilirubin increased and constipation
USE IN SPECIFIC POPULATIONS
Pediatric Use
- The safety and effectiveness of TRIKAFTA in patients with CF younger than 2 years of age have not been established
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