FDA Approves Orkambi for Children, Ages 6-11, with Cystic Fibrosis

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by Charles Moore |

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vertexlogoVertex Pharmaceuticals reported that the U.S. Food and Drug Administration (FDA) has granted approval for its cystic fibrosis (CF) drug Orkambi to be used to treat children, ages 6 to 11, who have two copies (one inherited from each parent) of the F508del mutation in the CFTR gene.

Having two copies of the F508del mutation is the leading cause of CF. According to the Cystic Fibrosis Foundation and UK CF Registry, approximately half of all people with cystic fibrosis in both the U.S. and the U.K. have two copies of the F508del mutation, identified by a simple genetic test.

Orkambi was previously approved by the FDA for the treatment of people ages 12 and older with two copies of the F508del mutation. This extended approval opens the treatment to  some 11,000 more CF patients in the U.S.

chodakewitzj“The ability to treat children as young as six who have the most common form of the disease is an important milestone as we pursue our goal to develop medicines for all people with CF,” said Jeffrey Chodakewitz, MD, executive vice president and chief medical officer at Vertex, in a press release. “We believe it is important to treat the underlying cause of the disease as early as possible in these patients.”

orkambilogoOrkambi is an oral combination drug (lumacaftor 200 mg/ivacaftor 125 mg) that targets the underlying cause of CF in people with this mutation. In this group, the defective CFTR gene causes production of an abnormal CFTR protein that disrupts water and chloride transport in the body — especially in the lungs and digestive tract — resulting in poor flow of salt and water into and out of cells, and leading to a build up of abnormally thick, sticky mucus that can cause chronic lung infections, and other severe respiratory and digestive problems. CF currently affects approximately 75,000 people in North America, Europe, and Australia.

Lumacaftor is a CFTR corrector, designed to increase the amount of mature CFTR protein at the cell surface by targeting and changing the processing and trafficking defect of the F508del CFTR protein, attempting to facilitate its transport to the cell membrane so as to increase the amount of functional protein present.

Ivacaftor (trade name Kalydeco) is a CFTR potentiator, meaning that it is designed to enhance the function of the CFTR protein once it reaches the cell surface. Ivacaftor allows a malfunctioning protein to interact normally with a cell membrane, which acts as a gateway, allowing for chloride transport in and out of the cell. Ivacaftor relies on proper protein transport to the cell membrane, without which it has no beneficial effect.

In pediatric patients ages 6-11, two Orkambi tablets (each containing lumacaftor 100mg/ivacaftor 125mg) are taken orally every 12 hours — once in the morning and once in the evening — with fat-containing food.

The FDA approval for younger children is based on data from a open-label Phase 3 clinical safety study of Orkambi that was presented at the 39th European Cystic Fibrosis Society Conference at Basel, Switzerland, in June. The data will also be presented at the 30th Annual North American Cystic Fibrosis Conference, set for Oct. 27–29 in Orlando, Florida.


Vertex also announced plans to submit a Marketing Authorization Application (MAA) allowing for Orkambi’s use in children ages 6 through 11 with two copies of the F508del mutation in the European Union in the first half of 2017. The application will be based on data from a Phase 3 efficacy study, in which the primary endpoint is absolute change in lung clearance index (LCI). Results from this trial are expected by the close of this year.

cfflogoVertex, founded in 1989, initiated its CF research program in 2000 as part of a collaboration with the Cystic Fibrosis Foundation Therapeutics (CFFT), a nonprofit drug discovery and development affiliate of the Cystic Fibrosis Foundation. Orkambi was discovered by Vertex as part of this collaboration.

For additional information and the latest updates from the company, visit: www.vrtx.com.

The 98-page FDA briefing document on Orkambi can be found here:

The U.S. Food and Drug Administration (FDA)
Vertex Pharmaceuticals Inc.
Cystic Fibrosis Foundation Therapeutics, Inc. (CFFT)