Real-world Use of Kalydeco for CF Highly Effective, Large-scale Analysis Shows

Kalydeco treatment led to fewer deaths, transplants, hospitalizations, and exacerbations in people with cystic fibrosis (CF) compared to patients who did not receive the therapy, according to a five-year, real-world analysis of patient registries in the U.S. and U.K. 

The results of the analysis were published in the journal Pulmonary Therapy, under the title, “Real-World Outcomes Among Patients with Cystic Fibrosis Treated with Ivacaftor: 2012–2016 Experience.”

CF is caused by mutations in the CFTR gene that result in a faulty CFTR protein that controls the flow of charged salts (ions), such as chloride, in and out of cells. While some mutations lead to a completely inactive CFTR protein, mutations called “gating mutations” block the passage of ions through the CFTR channel by causing the “gate” to be stuck in the closed position at the cell surface. 

Kalydeco (ivacaftor) is a treatment developed by Vertex Pharmaceuticals that works by keeping the gate open longer, effectively enhancing the activity of the CFTR protein. 

The therapy was approved by the U.S. Food and Drug Administration (FDA) in 2012 and later in Europe. Since it has become available, information about its effectiveness and associated adverse side effects has been collected and housed in CF patient registries. 

To better understand the real-world effects of Kalydeco treatment, researchers at Vertex, in collaboration with colleagues at the U.S. Cystic Fibrosis Foundation and the U.K. Cystic Fibrosis Trust, conducted an analysis of two of the largest CF patient registries: the U.S. Cystic Fibrosis Foundation Patient Registry (CFFPR), and the U.K. Cystic Fibrosis Registry (CFR).

This research was conducted as a post-marketing commitment to the European Medicines Agency and is described in the European Union Register of Post-Authorization Studies (EUPAS4270). 

The researchers evaluated patients treated with Kalydeco and compared the outcomes to a group of age- and gender-matched CF patients who never had  received the therapy. 

Patients in each registry were analyzed separately and in two parts, either annually for five years focusing on safety and patient outcomes during a single year, or overtime to assess disease progression. Clinical endpoints (goals) included mortality, organ transplants, hospitalizations, and pulmonary exacerbations (defined as episodes requiring intravenous antibiotics).

Of those in the U.S. registry, the number of CF patients receiving Kalydeco increased from 807 during year 1 (2012) to 1,858 during year 5 (2016). In the U.K. registry with four years of data, the number of CF patients increased from 307 during year 1 (2013) to 462 during year 4 (2016).

Results showed that five years of Kalydeco use in the U.S. led to a significant decrease in the risk of mortality compared with no treatment — a relative risk of 0.43 in 2012 (meaning a relative risk reduction of 57%) and 0.41 in 2016 (relative risk reduction of 59%). The results matched the four years of Kalydeco use in the U.K. as well — relative risk of 0.45 in 2013 and 0.47 in 2016. 

Similarly, compared to those not taking the therapy, patients taking Kalydeco had a significantly lower risk of a transplant — relative risk of 0.22 in 2012 and 0.29 in 2016 (meaning a relative risk reduction of 78% and 71%, respectively). Similar results were seen in the U.K. registry — relative risk of 0.24 in 2016).

Reductions in the annual risk of other clinical outcomes, including hospitalizations and pulmonary exacerbations, also were found in the two registries. 

Despite the variation in risk estimates from year to year, which was not unexpected given the changes in patient composition over time, the outcomes were consistent through the years in both registries. Furthermore, these results stand even with different definitions of hospitalizations used by the U.S. and U.K. registries. 

Finally, no new safety concerns were identified with using Kalydeco. 

Overall, the results of this study are consistent with a similar real-world analysis of a smaller number of CF patients in the U.S. and the U.K.

“Overall, patients treated with [Kalydeco] had consistently favorable clinical outcomes relative to their untreated comparators, and no new safety concerns were identified,” the researchers wrote.

“These data demonstrate the long-term impact of highly effective CFTR modulation with [Kalydeco],” they added.