Shapiro, Shelley

AbstractInhaled treprostinil is an approved therapy for pulmonary arterial hypertension (PAH) and pulmonary hypertension associated with interstitial lung disease in the United States. Studies have confirmed the robust benefits and safety of nebulized inhaled treprostinil, but it requires a time investment for nebulizer preparation, maintenance, and treatment. A small, portable treprostinil dry powder inhaler has been developed for the treatment of PAH. The primary objective of this study was to evaluate the safety and tolerability of treprostinil inhalation powder (TreT) in patients currently treated with treprostinil inhalation solution. Fifty‐one patients on a stable dose of treprostinil inhalation solution enrolled and transitioned to TreT at a corresponding dose. Six‐minute walk distance (6MWD), device preference and satisfaction (Preference Questionnaire for Inhaled Treprostinil Devices [PQ‐ITD]), PAH Symptoms and Impact (PAH‐SYMPACT®) questionnaire, and systemic exposure and pharmacokinetics for up to 5 h were assessed at baseline for treprostinil inhalation solution and at Week 3 for TreT. Adverse events (AEs) were consistent with studies of inhaled treprostinil in patients with PAH, and there were no study drug‐related serious AEs. Statistically significant improvements occurred in 6MWD, PQ‐ITD, and PAH‐SYMPACT. Forty‐nine patients completed the 3‐week treatment phase and all elected to participate in an optional extension phase. These results demonstrate that, in patients with PAH, transition from treprostinil inhalation solution to TreT is safe, well‐tolerated, and accompanied by statistically significant improvements in key clinical assessments and patient‐reported outcomes with comparable systemic exposure between the two formulations at evaluated doses (trial registration: clinicaltrials.gov identifier: NCT03950739).

BackgroundThe DelIVery for Pulmonary Arterial Hypertension clinical trial was a multi‐center, prospective, single arm, Investigational Device Exemption study utilizing a fully implantable, programmable intravascular delivery system consisting of a pump and a catheter for intravenous treprostinil. The study met its primary endpoint and demonstrated that the intravascular delivery system significantly reduced catheter related complications at 22,000 subject‐days of follow‐up compared with a predefined objective performance criterion. Here we summarize the results obtained during a 6.4‐year follow‐up period.MethodsThroughout study follow‐up, participants had clinic visits and medication refills at least every 12 weeks (dependent on the subjects’ dose). All adverse events and intravascular delivery system complications were evaluated and recorded.ResultsSixty pulmonary arterial hypertension subjects were followed post device implantation for approximately 282 patient‐years (range 87 days to 6.4 years). Of the 60 subjects, 14 died (1 related to intravascular delivery system pump failure), 2 withdrew after lung transplants, and 2 withdrew due to pump pocket infection. No catheter‐related bloodstream infections, catheter thrombosis or occlusions, or catheter kinks occurred through 282 patient‐years. Two participants had adverse events of abdominal pain, rash, due to subcutaneous treprostinil “leaks” after one catheter puncture and one catheter laceration during pump refill and replacement, respectively. Eight pump failure events occurred: seven pump motor stalls and one early replacement (faulty battery).ConclusionDelivery of treprostinil with an intravascular delivery system is a safe alternative to an external delivery system, while providing enhanced life experiences. To preserve the risk–benefit ratio, treatment at specialized pulmonary arterial hypertension centers is recommended until training is disseminated at other sites.