Proteostasis announces progression CF study to longer duration studies
Proteostasis Therapeutics announced updates across the company's later stage development programs in CF, including PTI-428, a cystic fibrosis transmembrane conductance regulator, CFTR, amplifier, PTI-801, a new generation CFTR corrector, and PTI-808, a CFTR potentiator. Proteostasis announced that it has completed dosing of 19 patients as part of the ongoing Phase 1/2 study designed to evaluate the safety and pharmacokinetics of PTI-428, the company's CFTR amplifier. PTI-428 was administered together with background Orkambi or as the only CFTR modulator therapy in CF subjects over a 14-day period. The trial met its primary safety and pharmacokinetic endpoints, confirming PTI-428's safety, tolerability and lack of clinically meaningful drug-drug interaction with ivacaftor and lumacaftor. "Preliminary data suggests that PTI-428 continues to demonstrate a favorable safety and pharmacokinetic profile, which has enabled the initiation of Phase 2, enrolling CF subjects on background Orkambi taking PTI-428 or placebo for 28 days," said Meenu Chhabra, President and CEO of Proteostasis Therapeutics. "We continue to make meaningful progress with all three components of our proprietary triple combination: with the support of US and EU patient advocacy groups for the PTI-801 protocol, we are eligible to begin screening and enrolling CF subjects on background Orkambi and 40 clinical sites in the US, Canada and EU have been identified or are in process of activation; enrollment continues in our 28-day study of PTI-428 across 14 active clinical sites in the US, with activation of another 23 sites in both the US and EU in process; and we have initiated a Phase 1 study of PTI-808 in healthy volunteers." In the Phase 1 portion of the PTI-428 study, 11 subjects in the Orkambi cohort and eight in the PTI-428 monotherapy cohort were enrolled, with each group enrolling 2 placebo subjects. All adverse events (were mild or moderate and none occurred in more than one subject. There were no hematology-related adverse events and no serious adverse events reported. Safety endpoints evaluated included lung function as measured by forced expiratory volume in one second, although the study was not designed to show a statistically significant difference. In the subjects who received PTI-428 in addition to their background Orkambi, there was no significant improvement of FEV1 compared to placebo, although there was a numerical increase in FEV1 at day 7. Measurements of sweat chloride and mRNA in nasal mucosa were used as exploratory biomarkers but the changes were not significant nor correlated with lung function changes. Ms. Chhabra added, "While confirming the safety of PTI-428, the phase 1 portion of this study was not expected to demonstrate efficacy over a 7-day dosing period, as PTI-428, as a CFTR amplifier, is designed to deliver substrate to correctors and was investigated in combination with Orkambi, whose signal of efficacy required a 28-day study. As a result, we look forward to generating data in our 28-day proof-of-concept study to begin understanding the activity profile of PTI-428." Proteostasis is enrolling patients in the Phase 2 safety and efficacy portion of the study, which explores PTI-428 dosed over a 28-day period, and preliminary data is expected in Q4 2017.