Orkambi Helps to Promote Glucose Tolerance in CF Patients, Study Finds

Orkambi (ivacaftor/lumacaftor) can improve glucose tolerance in people with cystic fibrosis, a small study in patients either at risk of or newly diagnosed with diabetes suggests.

The study, “Effect of one-year lumacaftor–ivacaftor treatment on glucose tolerance abnormalities in cystic fibrosis patients,” was published in the Journal of Cystic Fibrosis.

Glucose intolerance is an umbrella term that refers to high levels of glucose (sugar) in the blood, which can be an early sign of diabetes. This can be a problem in people with CF, since the pancreas (which helps regulate blood sugar) is affected in this disease.

Indeed, cystic fibrosis-related diabetes (CFRD) is one of the most common non-lung manifestations of CF, and is associated with poorer health outcomes.

Orkambi, marketed by Vertex Pharmaceuticals, is an approved treatment for people with CF who have two copies of the F508del mutation in the CFTR gene — the most common CF-causing mutation worldwide.

Previous clinical trials demonstrated that Orkambi can improve lung function parameters in people with CF. However, whether this medication also has benefits related to glucose tolerance remains unclear.

Researchers in France enrolled 40 CF patients in a clinical trial, called GLUCORRECTOR (NCT03512119), testing the effects of Orkambi treatment for one year on their glucose levels.

Participants (average age of 24, range 12 to 61) underwent oral glucose tolerance tests (OGTT) before and after treatment (one year later). These tests involve drinking a sugary solution, and then having blood glucose levels measured after one or two hours. For this study, two-hour OGTT values were used to determine glucose tolerance status.

At enrollment, 31 (78%) of these patients had glucose intolerance, while the remaining nine (22%) were newly diagnosed with CFRD.

After one year of Orkambi’s use, 50% (20 patients) showed normal glucose tolerance; 16 (40%) had glucose intolerance, and four (10%) had CFRD. Overall, 57.5% of trial participants (23 patients) improved their glucose tolerance.

The average two-hour OGTT values were significantly lower after one year of treatment -— 139 versus 171 mg/dL at baseline. One-hour OGTT values did not differ significantly after one year of treatment.

In line with previous research, results also showed significant improvements in lung function with Orkambi treatment. Namely, patients’ average forced vital capacity (FVC; a measure of lung function) rose from 2.85 to 3.12 liters.

It is important to note that, since the study did not include a placebo group, it is not possible to exclude a placebo effect. Previous research has also shown that blood glucose levels can fluctuate in people with CF in the absence of treatment, simply due to the natural course of the disease.

Thus, researchers emphasized that further studies are needed to confirm these results. Nonetheless, given what is already known about Orkambi from data in clinical and pre-clinical studies, the team believes that Orkambi does help to improve glucose tolerance.

“In conclusion, a positive lumacaftor–ivacaftor [Orkambi] treatment impact was demonstrated in CF patients with early AGT [abnormalities in glucose tolerance],” the researchers wrote.

Vertex gave funding support to this study, but “the sponsor did not participate in the article preparation, study design, collection, analysis, [or] data interpretation,” it notes.

Part of these results were presented at the 41^st European Cystic Fibrosis Society (ECFS) Conference in 2018.