Dupilumab shows long-term efficacy in asthma patients

 

An open-label extension study found a consistent safety profile and a maintained efficacy of dupilumab over up to 96 weeks. The LIBERTY ASTHMA TRAVERSE trial included asthma patients with uncontrolled moderate-to-severe asthma who had been enrolled in phase 2 and 3 randomised controlled trials for dupilumab treatment [1]. On the other hand, fevipiprant for therapy of severe asthma did not reach significance in the primary objective of the LUSTER-1 and LUSTER-2 trials [2].

The LIBERTY ASTHMA TRAVERSE trial included 2,282 patients from 4 parent studies: QUEST (phase 3), DRI (phase 2b), EXPEDITION (phase 2a), and VENTURE (phase 3) [1]. VENTURE assessed the IL-4 receptor alpha antagonist dupilumab for the treatment of asthma patients taking oral corticosteroids (OCS). In the open-label extension study, all patients were treated with add-on 300 mg of dupilumab every second week. Due to an amendment to the study design, 96% of the subject received therapy over 48 weeks and 54% over 96 weeks during the long-term extension. Dr Michael Wechsler (National Jewish Cohen Family Asthma Institute, USA) presented data from DRI, QUEST, and VENTURE for the safety findings and efficacy data for the non-OCS dependent patients from DRI and QUEST.

The primary endpoint of the extension study was the rate of patients with any kind of treatment-emergent adverse events up to week 96. Secondary endpoints included annualised severe exacerbation rate and forced expiratory volume over 1 second (FEV₁). “The dupilumab safety profile of the open-label extension was consistent with that in the previously published shorter duration parent studies,” said Dr Michael Wechsler (National Jewish Cohen Family Asthma Institute, USA). A treatment-emergent AE emerged in 76.3% to 87.6% of patients in the different groups; the most common included nasopharyngitis (17.5%-25.9%), bronchitis (9.3%-19%), and injection-site erythema (2.2%-23.4%). Serious treatment-emergent AE occurred in 9.3%-12.6% of participants, and 2.3%-5.6% of treatment-emergent AEs led to permanent discontinuation of dupilumab.

As for exacerbations in the open-label phase, the unadjusted annualised severe exacerbation rate ranged from 0.31-0.35 in non-OCS dependent patients. The corresponding values for dupilumab-treated patients at the end of the parent studies DRI and QUEST were 0.31-0.69 and 0.48-0.56, respectively. In DRI and QUEST, the baseline values for FEV₁ were 1.79-1.86 litres and 1.75-1.78 litres, respectively. “By week 96 of the open-label extension, absolute mean FEV₁ ranged from 2.02-2.12 litres representing a 13%-22% mean percent change from parent study baseline in the overall population,” stated Dr Wechsler.

He concluded that “long-term treatment with dupilumab was generally well tolerated. Patients exposed to dupilumab for up to 96 weeks, demonstrated maintenance in the clinical efficacy that was observed in the parent studies, including a persistently low exacerbation rate and sustained improvements in lung function.”

Disappointing results of the LUSTER trials

The phase 3 LUSTER-1 and LUSTER-2 studies evaluated patients with severe asthma, including those with high blood eosinophils, treated with GINA step 4 and 5 therapy [2]. Results of the over 1,700 patients randomised within both studies revealed a favourable safety and tolerability profile of the PGD2-receptor antagonist fevipiprant compared with placebo. However, in terms of efficacy, the reduction in exacerbations and improvements in lung function observed were only numerical and did not meet statistical significance.

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1. 
   
   1. Wechsler M. Dupilumab long-term safety and efficacy in patients with asthma: LIBERTY ASTHMA TRAVERSE. LBA 4613, ERS International Virtual Congress 2020, 7-9 Sept.
   2. Brightling CE. LUSTER-1 and -2: randomised controlled trials of fevipiprant in severe asthma. LBA 4614, ERS International Virtual Congress 2020, 7-9 Sept.

 



Posted on 29 October, 202023 February, 2021