Trikafta , a pioneering medication in the treatment of Cystic Fibrosis (CF), is the culmination of nearly two decades of research and development by Vertex Pharmaceuticals. Upon receiving FDA approval in 2019, Trikafta became one of the most important drugs for CF treatment, due to its ability to target the most common genetic mutations (Cystic Fibrosis Transmembrane Conductance Regulator – CFTR). CFTR is a gene that encodes for a protein responsible for transporting chloride (Cl-) and bicarbonate (HCO₃⁻) ions across cell membranes, playing a crucial role in maintaining ion and water balance. This protein is present in organs such as the lungs, pancreas, liver, and intestines)

History of Development

Trikafta completed its phase III clinical trials in 2019 and was officially approved by the FDA for CF treatment in October 2019. Following the FDA’s approval, regulatory agencies in several other countries recognized Trikafta, including in Australia, Canada, and Europe (where it is sold under the name Kaftrio),…

18/10/2019, FDA approved Trikafta for patients aged 12 and older who have at least one F508del mutation in their CFTR gene (the most common mutation causing cystic fibrosis). This mutation is found in approximately 90% of CF patients and results in the loss of a phenylalanine amino acid at position 508, causing improper folding of the CFTR protein, preventing its transport to the cell surface. As a result, CFTR function is disrupted, leading to thick, sticky mucus in the lungs and other organs, causing severe blockages and infections.

By 2021, the use of Trikafta was expanded to children aged 6 to 11, and most recently, approval was extended to children aged 2 to 5.

Key Development Milestones of Trikafta:

• • 2000: Research begins on the CFTR gene and the development of targeted therapies.
  • 2012: FDA approves Kalydeco, another CF treatment from Vertex, paving the way for combination therapy studies.
  • 2019: Trikafta receives rapid FDA approval due to strong clinical trial data and urgent need within the CF community.
  • 2021 – 2023: Expanded use for younger children (ages 2–5), marking significant progress in early treatment..

Components and Formulation:

Components : Trikafta is a combination of three active ingredients:

• • Ivacaftor: Enhances the function of the CFTR protein, helping open chloride channels to improve ion transport.
  • Elexacaftor and Tezacaftor: Aid in the proper folding and transportation of the CFTR protein to the cell surface.

Formulation:

• • Trikafta is available in film-coated tablet form and as oral granules for children aged 2 and older.
  • The film-coated tablets contain a combination of three active ingredients: elexacaftor, tezacaftor, and ivacaftor, along with a separate ivacaftor tablet to maintain treatment efficacy throughout the day. The usual dosing is divided into two administrations per day, with the majority of the active ingredients taken in the morning and ivacaftor in the evening​.

• • The film-coated tablet formulation protects the active ingredients from the digestive environment and supports optimal absorption through the intestines, crucial for ensuring the drug’s efficacy, especially for diseases related to protein dysfunction like CF.

• • The oral granules are specifically designed for children aged 2–5 with CF, addressing the need for an easier-to-consume form for those unable to swallow tablets. The granules contain the same active ingredients as the tablet form.

• • The oral granules are mixed with soft foods (e.g., mashed apples) or liquids for easy ingestion. Pre-measured packets ensure accurate dosing according to the patient’s age and weight.

Treatment:

• • Trikafta is designed to improve the function of the mutated CFTR protein, reduce symptoms, and prevent disease progression. It has demonstrated exceptional effectiveness in improving lung function and reducing sweat chloride levels, a key indicator of CF.
  • Trikafta is used to treat CF in patients aged 12 and older who have at least one F508del mutation in their CFTR gene.
  • The drug works by adjusting the activity of the CFTR protein.
  • Trikafta can be used in combination with other drugs, such as ataluren, sinapultide, lancovutide, depelestat, cobiprostone, pancrelipase, aquadeks, or inhaled glutathione.

Sales:

• • In 2023, Trikafta generated $8.9 billion in sales, marking a 16% increase compared to 2022. It is projected that the drug will surpass $10 billion in sales by 2024, driven by the expanding indications.
  • The extension of its use to children as young as 2 years old (approved by the FDA in April 2023) has significantly increased the number of patients receiving Trikafta treatment,

Future Developments:

Vertex is developing new therapies, such as vanzacaftor (a next-generation treatment), with hopes of further solidifying its position in CF treatment. This promises not only to maintain sales but also to expand treatment to rarer CF mutations.

References:

Trikafta’s Approval the Outcome of ‘20-year Journey That Started with a Dream’, Says Vertex CEO Jeffrey Leiden

https://www.pharmaceutical-technology.com/news/vertex-fda-cystic-fibrosis/

https://www.biospace.com/business/vertex-tops-q3-forecast-on-strength-of-cystic-fibrosis-sales-raises-full-year-revenue-guidance

https://www.trikafta.com/how-to-take-trikafta-granules

https://www.accessdata.fda.gov/drugsatfda_docs/nda/2023/217660Orig1s000NameR.pdf

https://www.trikaftahcp.com/dosing-and-administration

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