AllRock Bio Initiates Phase IIa Trial of First-in-Class Oral ROCK Inhibitor for Pulmonary Hypertension
Key Insights
AllRock Bio (search) has dosed the first patients in the Phase IIa ROCSTAR trial evaluating ROC-101 (search), a first-in-class oral pan-ROCK inhibitor for pulmonary arterial hypertension (search) and pulmonary hypertension (search) associated with interstitial lung disease (search).
The multi-center, open-label trial will enroll up to 40 patients and assess ROC-101 (search)'s ability to reduce pulmonary vascular resistance when combined with standard of care therapies, including sotatercept.
ROC-101 (search) targets both ROCK1 (search) and ROCK2 (search) kinases to address inflammatory, proliferative, and fibrotic remodeling underlying cardiopulmonary diseases with once-daily oral dosing.
AllRock Bio (search) has dosed the first patients in its Phase IIa ROCSTAR clinical trial investigating ROC-101 (search), a first-in-class oral pan-rho-associated protein kinase (ROCK) inhibitor for pulmonary hypertension (search). The multi-center, exploratory, open-label trial builds on prior Phase I data and will assess the tolerability, efficacy, and safety of the therapy in patients with pulmonary arterial hypertension (search) (PAH) or pulmonary hypertension associated with interstitial lung disease (search) (ILD-PH).
Novel Mechanism Targets Disease Pathways
By selectively inhibiting both ROCK1 (search) and ROCK2 (search) with high selectivity and potency, ROC-101 (search) targets inflammatory, proliferative, and fibrotic remodeling linked to PAH, ILD-PH, and other cardiopulmonary conditions, including Group 2 PH and idiopathic pulmonary fibrosis (search). The drug is designed to address the distinct, non-redundant roles of these kinases that are central to the pathological processes seen in cardiopulmonary diseases.
Pan-ROCK inhibition is anticipated to be highly complementary to other PH treatments, and the ROCSTAR trial is specifically designed to evaluate ROC-101 (search) in combination with standard of care therapies. The study includes a dedicated PAH arm for patients receiving sotatercept in combination with ROC-101.
Trial Design and Endpoints
The trial plans to enroll up to 30 PAH and 10 ILD-PH patients, World Health Organization (WHO) functional class II and III, who will each receive ROC-101 (search) combined with standard of care therapy. The primary endpoint is the change in pulmonary vascular resistance, measured by right heart catheterization from baseline to week 24 following treatment.
Secondary endpoints include six-minute walk distance, NT-proBNP, WHO functional class, and hemodynamic parameters. These measures will provide comprehensive assessment of the drug's impact on both objective cardiovascular parameters and functional capacity.
Promising Early Development Data
ROC-101 (search) demonstrated favorable pharmacokinetics supporting once-daily oral dosing in earlier studies. In a Phase I study in healthy volunteers, the drug was found to be safe, well-tolerated, and showed no evidence of hypotension, addressing a key concern with ROCK inhibition.
"We have successfully dosed our first patients with ROC-101 (search), including in combination with a stable dose of sotatercept," said Dr. Kate Steiner, VP, Head of Clinical Development at AllRock Bio (search). "We believe ROC-101, with its oral, once-daily dosing, has differentiated potential to address underlying disease mechanisms, further reduce pulmonary vascular resistance and improve functional outcomes for patients on top of existing therapies."
Addressing Significant Unmet Need
Pulmonary arterial hypertension (search) is a severe condition characterized by elevated blood pressure in the pulmonary arteries, impacting both the lungs and the right side of the heart. In PAH, the small pulmonary vessels undergo progressive narrowing, leading to elevated pulmonary arterial pressure that impedes blood flow through the lungs and places significant strain on the heart. Despite 16 approved drugs—including four primarily vasodilator classes—there continues to exist an unmet need for disease-modifying treatments in the current landscape.
Pulmonary hypertension (search) associated with interstitial lung disease (search) represents another area of high unmet need. ILD-PH is a distinct form of PH where blood pressure in the lungs increases in the setting of interstitial lung disease, which encompasses diseases like idiopathic pulmonary fibrosis (search) that impair lung structure and make breathing progressively harder. ILD-PH is associated with increased mortality and morbidity with worsening symptoms over time, and very limited treatment options are available.