Symdeko Seen to Favor Weight Gain, Limit Hospital Stays in Real-life Study

Symdeko (tezacaftor/ivacaftor) favors weight gain, shortens hospital stays, and reduces the number of days on antibiotics in patients with cystic fibrosis (CF), a real-world study of its use at a Scottish clinic reported.

However, no significant benefits in patients’ lung function were seen over about a year of follow-up.

The study, “Tezacaftor-ivacaftor use in routine care of adults with cystic fibrosis: a medicine use evaluation,” was published in the European Journal of Hospital Pharmacy.

Marketed as Symkevi in the European Union and U.K., Vertex Pharmaceuticals’ Symdeko is a combing therapy approved to treat CF in people who either have two copies of the F508del mutation in the CFTR gene — the most common disease-causing mutation — or one copy of the F508del mutation plus one mutation permitting residual function of the CFTR protein.

Its efficacy and safety of were demonstrated in three Phase 3 studies: EVOLVE (NCT02347657), EXPAND (NCT02392234), and the long-term and open-label EXTEND trial (NCT02565914). Symdeko was found to improve lung function and reduce respiratory exacerbations (acute increases in the severity of CF symptoms) while being generally safe and well-tolerated.

To gather data from routine clinical practice, researchers in Scotland conducted a longitudinal study assessing the Symdeko’s effect in adults with CF.

They looked at the medical records of patients using Symdeko for at least four weeks — and followed for at least one year — at The West of Scotland Adult Cystic Fibrosis Unit.

Of the 289 patients treated there, 121 (42%) were eligible for Symdeko based on their CFTR mutations. Due to manufacturer and other restrictions — the medicine was approved for Europe in 2017, but the pricing agreement that brought it into Scotland’s public health plan was reached in September 2019 — 45 (37%) received treatment with Symdeko for at least one month. Their median age was 30 (range 17 to 64), and 25 (56%) were male. About three-fourths (76%) had two copies of the F508del mutation.

Four patients stopped treatment for various reasons: two started a clinical trial, one switched to Kaftrio (ivacaftor/tezacaftor/elexacaftor;  Trikafta is U.S. brand name, also by Vertex) and one died. Each had used Symdeko for a median of 37 weeks (about nine months).

The researchers looked at changes in patients’ weight and lung function with the treatment. They found that Symdeko led to a mean increase of 1.8 kg in weight (about 4 lbs), which translated into a mean increase of 0.6 kg per square meters in body mass index or BMI, a measure of body fat.

However, small but not significant improvements were seen in predicted forced expiratory volume in one second (FEV1), a lung function test that measures the amount of air a person can forcefully exhale in one second. This finding was “disappointing,” the researchers wrote.

A possible reason, they suggested, was the poorer lung health of their patient group at the start of treatment. Adults in this study had a baseline FEV1 of 46%, while those in the EVOLVE and EXPAND trials that showed significant lung function gains had baseline measures of 60% and 62%, respectively.

Symdeko’s use also shortened hospital stays by a median four days, and lowered by a median 21 days the number of days that patients’ used antibiotics to treat respiratory exacerbations. Both these findings were statistically significant, the study reported, meaning they are not likely to be due to chance.

Hospital stays for these adults, as well as treatment with antibiotics and Symdeko, were given at this Scottish center, minimizing “variations” in the standard of care given that might affect study results.

Another study strength was that, despite its limited size, its patient “population was slightly larger than the numbers required to detect significant differences in a previous randomised controlled study (n=34) for differences in FEV1,” the researchers wrote.

As such, it showed that “the use of tezacaftor-ivacaftor [Symdeko] in routine practice for people with cystic fibrosis was associated with improvements in weight, as well as reducing the number of days people needed to spend in hospital and receive antibiotics,” the investigators wrote.

“Further work is needed to evaluate the cost-effectiveness of tezacaftor-ivacaftor and to assess the impact of this medicine on the quality of life of people with cystic fibrosis,” they added.