CF Patients Will Likely Benefit from Promising, New Data on Two Drugs

Vertex Pharmaceuticals recently revealed new clinical data on real-world long-term outcomes in cystic fibrosis (CF) patients treated with Kalydeco (ivacaftor). The company also presented data from a Phase 3 study evaluating Orkambi (lumacaftor/ivacaftor) for children with CF ages 6-11 years.

The results were available June 11-14 at the 39th European Cystic Fibrosis Society (ECFS) Conference in Basel, Switzerland.

Kalydeco is a disease-modifying drug approved to treat CF patients age two or older with specific mutations in the CFTR gene (the gene defective in CF patients). The drug is called a CFTR potentiator because it increases CFTR activity once it reaches the cell surface.

CF, a rare disease caused by the defective CFTR gene, leads to the accumulation of thick and sticky mucus, particularly in the lungs, and results in chronic lung infections and lung damage.

Vertex presented three posters on data from an ongoing, five-year observational study to address Kalydeco’s long-term safety in CF patients in a real-world setting. The studies included data from 1,265 patients from the United States CF Foundation Patient Registry, and 411 patients from the United Kingdom CF Registry. All information was collected through 2014.

Researchers determined that the combined registry data pointed to ivacaftor-derived disease relief in real-world settings.

In the U.S. registry, transplantation, hospitalization, pulmonary exacerbation, and risk of death were all significantly lower in ivacaftor-treated patients than in control subjects who never took ivacaftor. Similarly, in the U.K. registry, hospitalization and pulmonary exacerbation, but not transplantation and risk of death, were significantly lower in the patients who received ivacaftor.

Patients taking ivacaftor were also found to have lower incidence of CF-related diseases, such as diabetes or microbial infections.

Orkambi is an approved treatment for patients who have two copies of the F508del mutation in the CFTR gene.

The drug includes a combination of ivacaftor and lumacaftor, which helps overcome the problems in CFTR transcription and therefore increases the amount of mature CFTR protein at the cell surface. Although Orkambi is approved for CF patients aged 12 and older, approximately 2,400 children with ages 6-11 have two copies of the targeted mutation in the U.S. alone.

Vertex recently revealed data from its Phase 3 study that evaluated Orkambi’s safety and efficacy in 58 children, aged 6-11 years with two copies of the F508del mutation, who received treatment for 24 weeks. Patients showed lung function improvement, weight gain, reduction in sweat chlorine (the molecule that transported by CFTR), and improved lung clearance. The treatment was well tolerated with only 6.9% of the patients reporting serious adverse events.

Vertex has completed enrollment for another six-month Phase 3 study that will address the efficacy of Orkambi in 200 children aged 6-11 with two copies of the F508del mutation. The company believes that the study will support Orkambi approval in the European Union.

Dr. Jeffrey Chodakewitz, executive vice president and chief medical officer at Vertex, said in a press release that company scientists have worked many years creating drugs to address the disease’s underlying causes and to change the way CF is treated.

“As more data for Kalydeco and Orkambi become available, we are increasingly confident that treating the underlying cause of the disease slows its progression and results in a range of benefits across multiple measures of CF. We’re committed to continuing our efforts to help the two out of three people with CF who don’t currently have a medicine that treats the underlying cause of their disease,”  Chodakewitz said.