Press Releases<< Back
Aradigm Announces Detailed Third Party Evaluation Results for Apulmiq (FDA)/Linhaliq (EMA)
As previously reported,
Based on the TPE results, in ORBIT-4 the primary endpoint of median time to first PE was 231 days in the Apulmiq group and 158 days in the placebo group, a difference of 73 days. The treatment effect, based on a stratified unweighted log-rank test (stratified by sex and previous number of exacerbations in the past 12 months prior to randomization), was statistically significant (HR: 0.70; 95% CI: 0.52-0.96; p = 0.024). For the first secondary efficacy endpoint, there was a 37% reduction in the frequency of PEs over the 48-week treatment period in the Apulmiq treatment group as compared to the placebo group (negative binomial model; RR: 0.63; 95% CI: 0.48-0.82). This result was statistically significant (p=0.0007). In the analysis of the second secondary endpoint, a statistically significant 61% reduction in the frequency of severe PEs in the Apulmiq group compared with placebo was found (using the negative binomial model; RR: 0.39 (95% CI: 0.21-0.72; p=0.0024).
In ORBIT-3 the median time to first PE was 214 days in the Apulmiq treatment group as compared to 136 days in the placebo group. This increase of 78 days in the median time to first PE was similar to ORBIT-4 but was not statistically significant (HR: 0.97; 95% CI: 0.70-1.34; p = 0.84). For the first secondary efficacy endpoint, there was a 15% reduction in the frequency of all PEs over the 48-week treatment period in the Apulmiq treatment group as compared to the placebo group but it was not statistically significant (RR: 0.85 95% CI: 0.65-1.12; p=0.26). In the analysis of the second secondary endpoint, a statistically non-significant 19% reduction in the frequency of severe PEs in the Apulmiq group compared with placebo was found (p=0.51).
In ORBIT-3 and ORBIT-4, randomization of patients was stratified by the
number of PEs treated with antibacterials in the 12 months prior to
randomization: 2 to 3, 4 to 7, and more than 7 PEs. As agreed by the
Although the analyses had low statistical power, due to the relatively small size of the frequent exacerbator group (22% of the overall trial population) the primary and secondary PE results for the frequent exacerbators in both trials were concordant and demonstrated clinically meaningful outcomes in favor of Apulmiq. In ORBIT-4, for the frequent exacerbators the median time to first PE was 211 days in the Apulmiq group and 163 days in the placebo group, a difference of 48 days. In ORBIT-3 the median time to first PE was 163 days in the Apulmiq group and 74 days in the placebo group, a difference of 89 days. The treatment effect, based on the stratified unweighted log-rank test was also very similar in both trials (ORBIT-4 RR: 0.66; 95% CI: 0.35-1.24; p = 0.19 and ORBIT-3: RR: 0.66; 95% CI: 0.37-1.18; p = 0.16).
When analyzing the frequency of PEs in the frequent exacerbators, using the negative binomial model, clinically meaningful and statistically significant results in favor of Apulmiq were observed in ORBIT-4, with an estimated risk reduction of 49% for all PEs (RR = 0.51; 95% CI: 0.31-0.85; p = 0.0094). In ORBIT-3, the risk reduction for all PEs was 34% and of borderline significance (RR = 0.66; 95% CI: 0.43-1.00; p = 0.052). While the frequency analyses of severe PEs had large variability due to small sample size, the analyses for the frequency of moderate and severe PEs showed a consistent risk reduction between 55% in ORBIT-4 and 35% in ORBIT-3. In the frequent exacerbators with 4 or more PEs per year, the observed risk reductions of PEs translates to about 2 fewer PEs per patient per year. Such a reduction is of important clinical relevance because each individual PE may be an irreversible event, and frequent PEs have been shown to increase morbidity in NCFBE patients (Chalmers, 2018*).
There are no approved treatment options for the prevention or reduction
of PEs in NCFBE patients with chronic lung infection with P.
aeruginosa. We believe that frequency of PEs is a more appropriate
endpoint for measuring treatment effectiveness as compared to time to
first PE, and based on an
About Non-Cystic Fibrosis Bronchiectasis
NCFBE is a severe, chronic and rare disease characterized by abnormal
dilatation of the bronchi and bronchioles, frequently associated with
chronic lung infections. It is often a consequence of a vicious cycle of
inflammation, recurrent lung infections, and bronchial wall damage.
NCFBE represents an unmet medical need with high morbidity and mortality
that affects more than 150,000 people in the U.S. and over 200,000
Except for the historical information contained herein, this news
release contains forward-looking statements that involve risk and
uncertainties, including the risk that Apulmiq may not receive
regulatory approval or be successfully commercialized, as well as the
other risks detailed from time to time in the Company’s filings with the
More information about
* Chalmers JD, Aliberti S, Filonenko A, et al. Characterization of the “frequent exacerbator phenotype” in bronchiectasis. Am J Respir Crit Care Med. 2018;197(11):1410-20.
John M. Siebert, 510-265-8800
Interim Principal Executive Officer