Proteostasis Therapeutics Announces Positive Preliminary Results from Proprietary Doublet in Cystic Fibrosis Patients
These studies were designed to assess the safety, tolerability, and pharmacokinetics (PK) of PTI-801, a third-generation cystic fibrosis transmembrane conductance regulator (CFTR) corrector, PTI-808, a novel CFTR potentiator, and PTI-428, a novel CFTR amplifier, compared to placebo over a 14-day dosing period in CF subjects across dose levels of each modulator. Changes in sweat chloride (SC) concentration and in percent predicted FEV1 (ppFEV1) were assessed and evaluated as endpoints.
At the time of data cut, 21 subjects were randomized and treated in the first three dose cohorts of the doublet combination of PTI-801 (100 mg, 200 mg, 300 mg) and PTI-808 (50 mg, 100 mg, 300 mg) or received placebo. PK results were as expected and confirmed a once-a-day dosing profile for both PTI-801 and PTI-808. In terms of safety, the compounds were generally well tolerated. No pulmonary exacerbations were reported in the dosing or follow up period of the study.
A dose-dependent improvement in ppFEV1 and sweat chloride concentration was observed across cohorts. For ppFEV1, a maximum and statistically significant increase from baseline to day 7 of +6.3% and at day 14 of +5.9% was reported in the PTI-801 300 mg/PTI-808 300 mg dose cohort. A statistically significant increase from placebo was also noted from baseline to day 7 of +8.3% and at day 14 of +6.6% in this cohort. A statistically significant decrease in sweat chloride concentration from baseline was also observed at day 7 and at day 14 of approximately 13 mmol/L in the PTI-801 300 mg/PTI-808 300 mg dose cohort. The fourth and highest dose cohort, patients receiving PTI-801 (400 mg) and PTI-808 (300 mg), is ongoing, with data expected in the first quarter of 2019.
"Doublet combinations, the current standard of care for many CF patients, are the benchmark for current treatment in cystic fibrosis. These data are the first results seen using an entirely new CF doublet, compare favorably to standard of care, and demonstrate the potential of next-generation CFTR modulators to further improve outcomes in this disease," said
"The current improvement in ppFEV1 for standard of care doublets is on average 3%-4% in the F508del homozygous patient population," said
The Company also confirmed today that the first dose cohort using the Company's proprietary triplet combination of PTI-801, PTI-808 and PTI-428, a novel CFTR amplifier, is on track to deliver preliminary data in the fourth quarter of 2018, with complete data from the doublet and triplet cohorts expected in the first quarter of 2019.
Dual Track Development Strategy in CF
In addition to completed studies of PTI-801 and PTI-428 in patients on background Orkambi® therapy, and the ongoing study of the PTI doublet (PTI-808, PTI-801) and the PTI triplet (PTI-808, PTI-801 and PTI-428), Proteostasis is conducting separate studies of PTI-801 and PTI-428 in CF subjects on background Symdeko® therapy. Both studies are underway and are expected to read out in the first quarter of 2019.
In its totality, Proteostasis' clinical strategy is expected to inform a Phase 3 development path using PTI's proprietary product candidates either together and/or as add-ons to current standards of care. Based on the anticipated timing of study readouts across this portfolio of programs, the Company expects to be in a position to initiate Phase 3 studies within the next 12-18 months.
"We've taken a significant step forward in demonstrating the potential value of our proprietary combinations with this doublet data, and as our data package builds out across both doublet and triplet programs, we remain committed to bringing more choices in CFTR modulator combinations to the CF community," said
Ms. Chhabra added: "As part of our evaluation of these next steps, we will expand our exploration of partnering opportunities across our product portfolio and in various geographies, with the goal of bringing the resources and expertise to bear on a platform with transformative potential in cystic fibrosis."
Conference Call and Webcast
Proteostasis will hold a conference call and accompanying webcast today,
To the extent that statements in this release are not historical facts, they are forward-looking statements reflecting the current beliefs and expectations of management made pursuant to the safe harbor provisions of the Private Securities Litigation Reform Act of 1995. Words such as "aim," "may," "will," "expect," "anticipate," "estimate," "intend," and similar expressions (as well as other words or expressions referencing future events, conditions or circumstances) are intended to identify forward-looking statements. Examples of forward-looking statements made in this release include, without limitation, statements regarding the potential of our proprietary double combination therapy for the treatment of CF, the potential benefit to patients of our proprietary double combination therapy, expected presentations and expected timing of the initiation of, patient enrollment in, data from, and the completion of, our clinical studies and cohorts for our clinical programs. Forward-looking statements made in this release involve substantial risks and uncertainties that could cause actual results to differ materially from those expressed or implied by the forward-looking statements, and we, therefore cannot assure you that our plans, intentions, expectations or strategies will be attained or achieved. Such risks and uncertainties include, without limitation, the possibility final or future results from our drug candidate trials (including, without limitation, longer duration studies) do not achieve positive results or are materially and negatively different from or not indicative of the preliminary results reported by the Company (noting that these results are based on a small number of patients and small data set), uncertainties inherent in the execution and completion of clinical trials (including, without limitation, the possibility that FDA comments delay, change or do not permit trial commencement, or intended label, or the FDA requires us to run cohorts sequentially or conduct additional cohorts or pre-clinical or clinical studies), in the enrollment of CF patients in our clinical trials in a competitive clinical environment, in the timing of availability of trial data, in the results of the clinical trials, in possible adverse events from our trials, in the actions of regulatory agencies, in the endorsement, if any, by therapeutic development arms of CF patient advocacy groups (and the maintenance thereof), and those set forth in our Quarterly Report on Form 10-Q for the quarter ended June 30, 2018 and our other SEC filings. We assume no obligation to update or revise any forward-looking statements, whether as a result of new information, future events or otherwise.
Orkambi® and Symdeko® are trademarks of Vertex Pharmaceuticals Incorporated.
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