MF-IND: A potential new once-daily ICS-LABA combo option for asthma

A novel once-daily fixed-dose combination (FDC) of ICS-LABA* comprising mometasone furoate and indacaterol acetate (MF-IND) is superior over an ICS monotherapy of MF in improving lung function of patients with inadequately controlled asthma, the PALLADIUM study has shown — providing another once-daily FDC option for these patients.

High-dose MF-IND was also noninferior to high-dose fluticasone propionate–salmeterol xinafoate (FLU–SAL) twice daily, the approved standard of care for this group of patients. [Lancet Respir Med 2020;doi:10.1016/S2213-2600(20)30178-8]

“Retrospective studies [have] shown that once-daily ICS–LABA dosing regimens, compared with twice-daily dosing, were associated with improved adherence and lower risk of treatment discontinuation in patients with asthma,” said the researchers.

“[However,] most ICS–LABA FDCs require twice-daily dosing, with the exception of FF–VI** [which is] once daily,” they noted.

IND is a LABA with a rapid onset of action, which is sustained over 24 hours, whereas MF is a potent ICS — making them ideal candidates for development as once-daily FDC, the researchers explained. IND and MF has been approved, respectively, for COPD and asthma.

“This novel once-daily ICS–LABA FDC provides another effective option over twice-daily ICS–LABA for patients with inadequately controlled asthma … particularly in those patients who find a twice-daily treatment option to be burdensome,” the researchers pointed out.

Positive across outcomes

The global, double-blind, triple-dummy, phase III study involved 2,216 patients aged 12–75 years (mean age 47.9 years, 58 percent female) with inadequately controlled asthma, despite treatment with medium-/high-dose ICS or low-dose ICS + LABA. They were randomized 1:1:1:1:1 to high-dose (320 μg/150 μg) or medium-dose MF–IND (160 μg/150 μg) once daily; high-dose (800 μg) or medium-dose MF (400 μg); or high-dose FLU–SAL (500 μg/50 μg) twice daily.

After 26 weeks, MF-IND led to superior improvements in trough FEV₁ by 132 mL (p<0.001) for high-dose and by 211 mL for medium-dose (p<0.001), compared with the corresponding MF doses.

“The improvements were sustained at week 52,” the researchers reported.

Similar improvements were also seen among adolescents, which constitute 5 percent of the study population.

In addition, improvements in asthma symptom control, as measured by ACQ-7 score, were significantly greater with MF-IND vs MF monotherapy at 26 weeks (p<0.001 for comparison of combined doses of each treatment). In concordance, patients receiving MF-IND were more likely to respond to treatment compared with those on MF alone (76.3 percent vs 69.7 percent; odds ratio, 1.51; p<0.001).

Furthermore, high-dose MF-IND reduced reliance on SABA*** rescue medication compared with MF monotherapy, by 2.0 puffs and 1.6 puffs per week for high- and medium-dose comparison, respectively.   

“These results clearly show the beneficial effects of MF–IND on asthma control versus MF monotherapy, in line with previous studies comparing ICS–LABA with ICS monotherapy,” observed the researchers.

On par with standard comparator

When compared head-to-head against the approved standard-of-care FLU-SAL, high-dose MF-IND was noninferior to the corresponding high-dose standard comparator in improving trough FEV₁ at 26 weeks (p=0.101).

Similar finding was seen for ACQ-7 improvements at weeks 26 and 52.

Both high and medium doses of MF-IND were well tolerated in general, with no evidence of excess risk with the addition of a LABA in comparison to MF or FLU-SAL.

“This expands the spectrum of once-daily ICS–LABA inhalers, and might improve outcomes in asthma patients by simplifying treatment regimens and improving adherence,” said Dr Guy Brusselle of Ghent University Hospital, Belgium, in a linked commentary. [Lancet Respir Med 2020;doi:10.1016/S2213-2600(20)30305-2]

“Moreover, the availability of three dosing options (low-dose, medium-dose, and high-dose) provides physicians with an option to titrate among the doses, as needed.”