Inhibikase Therapeutics announced it will advance its lead candidate IKT-001 directly to a global pivotal Phase 3 clinical study for pulmonary arterial hypertension (PAH), bypassing a planned Phase 2b trial and potentially accelerating FDA approval by approximately three years.
The clinical-stage pharmaceutical company received FDA feedback through a Type C meeting that supports transitioning immediately to the Phase 3 study, named IMPROVE-PAH (IKT-001 for Measuring Pulmonary Vascular Resistance and Outcome Variables in a Phase 3 Evaluation of PAH). The study is expected to initiate in the first quarter of 2026.
Novel Prodrug Design Addresses Previous Limitations
IKT-001 is an investigational prodrug of imatinib mesylate, an anti-proliferative tyrosine kinase inhibitor. While imatinib demonstrated potential best-in-class improvements in pulmonary vascular resistance and 6-minute walk distance of 45 meters based on Phase 3 IMPRES and Phase 2 studies, high discontinuation rates impacted the results in previous trials.
"IKT-001 is a prodrug of imatinib which is engineered to realize the potential of imatinib in PAH and lower discontinuations in the forthcoming Phase 3 study," the company stated. The prodrug is designed with an expected improved gastrointestinal tolerability profile compared to imatinib.
Adaptive Phase 3 Study Design
The IMPROVE-PAH study will employ a two-part adaptive design. Part A will be a double-blind, placebo-controlled study in 140 patients with a primary endpoint of pulmonary vascular resistance at Week 24. Part B will use an identical format but focus on 6-minute walk distance at Week 24 in 346 patients.
The adaptive design offers several advantages, including a 12-week dose-titration phase designed to help patients reach the highest tolerable dose of IKT-001, uninterrupted enrollment between parts, and the ability to conduct sample size re-estimation for Part B based on Part A findings. The study will be conducted at approximately 180 sites worldwide.
Accelerated Development Timeline
Mark Iwicki, Chief Executive Officer of Inhibikase, emphasized the strategic advantage of the revised approach: "Our revised study plan for IKT-001 in PAH permits a single pivotal study format and thereby has the potential to advance our timeline to Phase 3 topline data readout and a potential NDA filing by approximately three years."
The company had originally planned to conduct a Phase 2b study in 150 subjects before advancing to Phase 3. The FDA's written responses now allow for the 12-week dose-titration phase, which the company believes will potentially allow patients to reach higher tolerable doses where imatinib has previously demonstrated the greatest benefit in exercise capacity and hemodynamics.
Addressing Unmet Medical Need
PAH is a progressive, life-threatening disease characterized by pulmonary vascular remodeling and elevated pulmonary vascular resistance that affects approximately 50,000 Americans. The condition arises from aberrant signaling through the Abelson Tyrosine Kinase and type III receptor tyrosine kinases, including platelet-derived growth factor receptors and c-KIT.
With over two decades of imatinib clinical experience and IKT-001's expected improved tolerability profile, Inhibikase believes this supports a potentially higher probability of success for the upcoming Phase 3 study.
