Orkambi - Lumacaftor / Ivacaftor

What is Orkambi - Lumacaftor / Ivacaftor used for?

Orkambi is a medicine used to treat cystic fibrosis in patients at least 12 years of age who carry a genetic mutation known as the F508del mutation. This mutation affects the gene that codes for a protein, known as the regulator of the transmembrane conductance of cystic fibrosis (CFTR), involved in the regulation of mucus production and digestive juices. Orkambi is used in patients who have inherited the mutation from both parents and are therefore carriers of both copies of the CFTR gene.

Cystic fibrosis is an inherited disease that has serious effects on the lungs and digestive system. It affects the cells that produce mucus and digestive juices. In cystic fibrosis, the secretions become dense and cause a blockage. Accumulation of dense and viscous secretions in the lungs is the cause of inflammation and chronic infections. In the intestine, blocking of pancreatic ducts slows the digestion of food and causes inadequate development. Orkambi contains the active ingredients lumacaftor and ivacaftor.

How is Orkambi - Lumacaftor / Ivacaftor used?

Orkambi can only be prescribed by a doctor with experience in the treatment of cystic fibrosis. It should only be prescribed to patients at least 12 years of age with an established F508del mutation on both copies of the CFTR gene.

Orkambi is available as tablets containing 200 mg of lumacaftor and 125 mg of ivacaftor. The recommended dose of Orkambi is two tablets twice a day, taken 12 hours apart with fat-containing foods, such as meals prepared with butter or oils, or foods containing eggs, cheese, nuts, whole milk or meat.

In patients with liver problems or taking certain drugs known to be strong CYP3A4 inhibitors, it may be necessary to reduce the dose of Orkambi.

How does Orkambi - Lumacaftor / Ivacaftor work?

Cystic fibrosis is caused by a mutation in the CFTR gene. This gene produces a protein known as "regulator of cystic fibrosis transmembrane conductance" (CFTR), involved in the regulation of mucus production and digestive juices. These mutations reduce the number of channels for the CFTR protein on the cell surface or affect its functioning. These channels serve for the transport of ions (atoms and molecules with electric charge) towards the inside and the outside of the cells. If the channels are defective, mucus and gastric juices can become abnormally dense and viscous.

One of the active ingredients contained in Orkambi, lumacaftor, increases the number of CFTR proteins on the cell surface, while the other, ivacaftor, increases the activity of the defective CFTR protein. This normalizes the transport of ions through the membrane channels, making the secretions less dense.

What benefit has Orkambi - Lumacaftor / Ivacaftor shown during the studies?

Orkambi has been shown to be effective in improving lung function in two main studies involving 1 108 cystic fibrosis patients aged 12 years or older with F508del mutation on both copies of the CFTR gene. In the studies Orkambi was compared to a placebo (a dummy treatment); both were added to the normal therapy given to patients. The main efficacy parameter was based on the percentage improvement of the FEV1 expected for the patient, a parameter indicative of the good functioning of the lungs.

The results of the first study showed that after 24 weeks of treatment, the patients who took Orkambi had an average improvement in FEV1 of 2.41 percentage points higher than those treated with placebo, while this value was 2, 65 in the second study.

Treatment with Orkambi also resulted in a reduction in the number of exacerbations that required hospitalization or antibiotic therapy. Overall, the number of exacerbations was reduced by 39% compared to placebo.

What is the risk associated with Orkambi - Lumacaftor / Ivacaftor?

The most common side effects with Orkambi (which may affect more than 1 in 10 people) are dyspnoea (shortness of breath), diarrhea and nausea (feeling sick). Serious side effects include liver problems, such as elevated liver enzymes, cholestatic hepatitis (bile accumulation resulting in inflammation of the liver) and hepatic encephalopathy (a brain disease caused by liver problems). Overall, these serious side effects occurred in more than 1 in 200 people during clinical trials.

For the full list of all side effects reported with Orkambi and the restrictions, see the package leaflet.

Why has Orkambi - Lumacaftor / Ivacaftor been approved?

The Agency's Committee for Medicinal Products for Human Use (CHMP) decided that Orkambi's benefits are greater than its risks and recommended that it be approved for use in the EU.

Although the beneficial effects of Orkambi were consistent in the studies conducted and similar to those of the medicines used to treat symptoms of cystic fibrosis, they turned out to be lower than those expected for a medicine that affects the mechanism of the disease rather than its symptoms . However, since the cystic fibrosis caused by the F508del mutation is particularly severe, the CHMP considered that the observed effects were clinically relevant for patients without alternative treatment options. Furthermore, the committee noted that Orkambi's benefits were maintained throughout the 48-week treatment period. The side effects of Orkambi mainly affected the bowel and respiratory function, and were generally considered mild to moderate and manageable.

What measures are being taken to ensure the safe and effective use of Orkambi - Lumacaftor / Ivacaftor?

A risk management plan has been developed to ensure that Orkambi is used as safely as possible. Based on this plan, safety information has been included in the summary of product characteristics and the package leaflet for Orkambi, including the appropriate precautions to be followed by healthcare professionals and patients.