Projects

TRIKAFTA (elexacaftor, ivacaftor and tezacaftor) for the Treatment of Cystic Fibrosis

TRIKAFTA is the first triple combination therapy containing elexacaftor, ivacaftor, and tezacaftor indicated for the treatment of cystic fibrosis (CF) in people aged 12 years and above and having a F508del mutation and one minimal function mutation.

Drug Name

TRIKAFTA (elexacaftor, ivacaftor, and tezacaftor)

Developer

Vertex Pharmaceuticals

Current Indication

Cystic fibrosis

Market Sector

Respiratory

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TRIKAFTA is the first triple combination therapy containing elexacaftor, ivacaftor and tezacaftor, indicated for the treatment of cystic fibrosis (CF) in people aged 12 years and above with an F508del mutation and one minimal function mutation.

Developed by Vertex Pharmaceuticals, the new drug application (NDA) for TRIKAFTA was accepted for review and granted priority review status by the US Food and Drug Administration (FDA) in August 2019. The FDA approved the drug in October 2019. The drug has also received breakthrough therapy and orphan drug statuses from the FDA.

TRIKAFTA is available as a fixed-dose tablet containing elexacaftor 100mg, tezacaftor 50mg and ivacaftor 75mg.

A marketing authorisation application (MAA) for the drug has also been submitted to the European Medicines Agency (EMA).

The company is evaluating the drug in a phase three trial for people aged between six and 11 years with F / MF and F / F mutations. It also plans to evaluate the efficacy of the drug in children below the age of six years in future studies.

Cystic Fibrosis disease cause and symptoms

Cystic fibrosis is a rare, progressive, life-threatening condition that results in the formation of thick mucus that affects the lungs, liver, gastro intestine (GI) tract, sinuses, sweat glands, pancreas and reproductive system.

The disease is caused by defective or missing cystic fibrosis transmembrane conductance regulator (CFTR) proteins that result from mutations in the CFTR genes. F508del mutation is the most common among 2,000 known mutations of CFTR genes.

The symptoms of cystic fibrosis include frequent infections, lung damage, the formation of cysts and chronic digestive problems.

TRIKAFTA’s mechanism of action

The elexacaftor and tezacaftor contained in TRIKAFTA bind to the CFTR protein and facilitate the cellular processing of F508del-CFTR. The combination helps in increasing the amount of CFTR protein delivered to the cell surface, while ivacaftor aids in the gating of the CFTR protein at the cell surface.

The combined effect of the three drugs boosts the amount and function of F508del-CFTR at the cell surface.

Clinical trials on TRIKAFTA

FDA approval of TRIKAFTA comes from two randomised, double-blind phase three studies conducted in cystic fibrosis patients aged 12 years and above with at least one F508del mutation.

“Developed by Vertex Pharmaceuticals, the new drug application (NDA) for TRIKAFTA was accepted for review and granted priority review status by the US Food and Drug Administration (FDA) in August 2019.”

The first trial was a 24-week placebo-controlled trial that enrolled 403 patients. The second trial was a four-week active-controlled trial that enrolled 107 patients with two similar F508del mutations.

The per cent predicted forced expiratory volume in one second (ppFEV1), a measure of cystic fibrosis lung disease progression, was the primary endpoint of both the studies. In the first trial, TRIKAFTA increased the ppFEV1 by 13.8% from baseline and by 10% in the second trial.

TRIKAFTA was also effective in increasing sweat chloride, the number of pulmonary exacerbations and body mass index in the first trial. The safety profile of the drug comes from data of 510 cystic fibrosis patients who participated in the two trials.

The most common adverse reactions observed during the trials included headache, abdominal pain, rashes, respiratory tract infections, nasal congestion, rhinitis, rhinorrhoea and sinusitis.

Marketing commentary on Vertex Pharmaceuticals

Based in London, UK, Vertex is a biotechnology company involved in the development of transformative medicines for serious diseases.

The company has a promising pipeline of investigational drugs indicated for conditions such as sickle cell disease, pain, Duchenne muscular dystrophy and kidney diseases.

Vertex operates research and development (R&D) facilities across North America, Europe, Australia and Latin America.

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