Elevair Endobronchial Coil System Rejected by FDA

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Committee: The Anesthesiology and Respiratory Therapy Devices Panel of the Medical Devices Advisory Committee

Indication: bronchoscopic placement of ELEVAIR Coils in patients with severe emphysema (homogeneous and/or heterogeneous) and severe hyperinflation to improve quality of life, lung function, and exercise capacity..

Drug/Device: Elevair Endobronchial Coil System

Sponsor: PneumRx, Inc.

Links:

Vote Results: 5 Yes, 7 No

Elevair Endobronchial Unique challenges:

PneumRx’s Elevair, an endobronchial coil system, a first-of-its-kind device, failed to obtain approval from FDA. In a series of close votes, the panel voted that the device was safe in a 7-5 split. However, an 8-3 vote found that the overall benefits did not outweigh the risks. What’s more, the panel voted by a 5-7 margin that the device was not effective for its targeted patient group.

 

The Elevair device is a nitinol endobronchial coil intended to be deployed bronchoscopically to reduce lung volume in patients with severe emphysema. The company submitted an application for premarket approval with the FDA, backed by clinical evidence from a trial of the device. The assessor blinded, prospective, randomized, multi-center Renew trial examined the use of the device over a year, and included four years of additional follow-up visits with 315 subjects.

 

The statistical analysis plan provided by applicant seems well designed to achieve statistically significant results for primary endpoint and secondary endpoints. The study demonstrated a statistically significant absolute difference in 6MWT between the treatment and control arm  and  statistically significant improvement in the secondary endpoints of FEV1, 6MWT responder rate and SGRQ at 12 months..

 

However, these significant results were not supportive to convince clinical experts due to two main reasons. First of all, lack of data for pulmonary rehabilitation maintenance and Open-label design affecting patient reported outcomes such as SGRQ, which are considered as potential confounders. Without analysis of confounders, the interpretation of these results remains uncertain. Secondly, lack of results correlation between US site and Out of US site, as well as conflicting results between single arm observational crossover study and pivotal study casted a shallow over the interpretation of treatment effect.  Further, Pooled results that pooling the US and OUS data for an overall assessment of effectiveness of coil treatment may not be generalized to US population.  Clinical study design may need a review to provide supportive evidence to interpretation of treatment effect.

 

Safety:

 

Safety of the coil treatment with regards to device related mortality, increased risk of COPD exacerbations, pneumonia, and pneumothorax in relation to underlying disease is not favorable.

There were more adverse events in the treatment arm at 12 months in comparison to the control arm. In long term safety follow up, the most common AEs were COPD exacerbation and lower respiratory tract infection, while both were significantly higher in treatment arm than in control arm at 12 months analysis, (69.7% vs 58.0%) for former and (32.9% vs 8.9%) for latter,  respectively . Other AEs, such as pneumothorax (11.6% in treatment arm versus 0.6% in the control arm) and dyspnea (21.3% rate of versus 7.6% in the control arm), further raised a concern about increased risk of using the device to underlying diseases.

 

Risk /Benefit:

 

Given significant higher AEs rate in treatment arm versus in control arm and

the majority of the deaths in the treatment arm were possibly or probably device and/or procedure related, thus, whether or not the benefits outweigh the risks remains questionable.

PneumRx, Inc. plans to continue to work with the FDA to address the issues raised by the recent board decisions as part of the premarket approval process.