Positive Phase 1 results support the advancement to LYRIC-HF Phase 2 proof-of-concept clinical trial in heart failure patients
Qanatpharma, a clinical-stage biopharma company specializing in microvascular research and medicine, announced publication of topline results from its Phase 1 bioequivalence and food effect trial that assessed the pharmacokinetics of Lumacaftor in 35 healthy adult volunteers (NCT05968612). The results have now been published with Springer Nature in Drugs in R&D, titled “Demonstrating Bioequivalence for a Lumacaftor Monosubstance Formulation Versus Orkambi® (Lumacaftor/Ivacaftor) in Healthy Subjects”.
Classically used for the treatment of cystic fibrosis, QP is exploring an innovative use for the CFTR-stabilizing compound Lumacaftor to treat brain blood flow deficits that are widely observed in diseases like heart failure (HF) and subarachnoid hemorrhage (SAH) and contribute to the development of functional and cognitive impairments. QP’s initial discovery demonstrated that CFTR-stabilizing compounds correct the molecular deficits that compromise cerebral microvascular function and hence, cerebral blood flow autoregulation in disease models, which provided proof of principle for clinical application.
“As QP’s first clinical study, it’s very encouraging to have such clear results going into our Phase 2 LYRIC-HF trial, where we aim to establish proof-of-concept for use of CFTR-stabilizing therapies to improve cerebral perfusion in heart failure - a major contributor to poor clinical outcome in these patients” - Dr. Steffen-Sebastian Bolz, Chief Medical and Scientific Officer of Qanatpharma
Most clinical studies have been conducted using the combination drug Orkambi® (lumacaftor/ivacaftor), which is currently approved for treatment of cystic fibrosis. QP is developing a lumacaftor monosubstance therapy formulation for application in HF. This Phase 1 study confirms that QP's lumacaftor therapy aligns with the pharmacokinetic and safety profile that has been established for lumacaftor in the reference product (lumacaftor/ivacaftor). Lumacaftor alone was well-tolerated in healthy volunteers, with no severe symptoms attributed to the treatment. Paired with efficacy data in disease models and an encouraging safety profile, the Phase 1 results support the company’s repurposing strategy for rapidly advancing to Phase 2 proof-of-concept studies in HF.
Topline results and observations
Bioequivalence was achieved: lumacaftor pharmacokinetics are bioequivalent when consumed as a monosubstance formulation versus the reference combination product Orkambi® (lumacaftor/ivacaftor).
Food-effect observed: Lumacaftor pharmacokinetics are enhanced when consumed with a meal.
Lumacaftor monotherapy was well-tolerated at a single dose of 400 mg.
No serious adverse events reported: Treatment emergent adverse effects were mild to moderate in nature and resolved without sequelae.
No safety findings of concern: Safety parameters and vital signs within normal range, returned to normal after repeated measurements, or were deemed not clinically significant.
Phase 1 Trial Design
The Phase 1 single-dose, randomized, open-label, three-way crossover was conducted at a single-center in Toronto, Canada. Subjects were randomized to one of three treatment sequences to evaluate a single oral dose of QP’s Lumacaftor monosubstance tablet (2×lumacaftor 200mg) under fasted and fed conditions, and a single dose of the reference product (2×lumacaftor 200 mg/ivacaftor 125 mg) under fed conditions. Following each dose, blood samples were collected at 17 timepoints over a 72-hour period (pre-dose (0) at 0.25, 0.5, 0.75, 1, 2, 3, 4, 5, 6, 7, 8, 9, 12, 24, 48, and 72).
Company Summary
Qanatpharma (QP), a Phase 2 clinical-stage biopharma company specializing in microvascular research and medicine, has identified and partly validated a portfolio of protein targets involved in the regulation of resistance artery tone in both the cerebral and peripheral circulation. These targets have potential applications in multiple diseases where microvascular dysfunction is a central feature of the pathology, including life-limiting conditions such as heart failure, hemorrhagic stroke and hypertension. Through its collaborative approach towards building innovation capacity and partnering with top scientific and clinical centers worldwide, QP manages a microvascular pipeline that spans from target discovery and validation via AI-driven drug development to preclinical studies and, ultimately, clinical trials.
