Contineum Therapeutics Reports Positive Phase 1b Results for PIPE-791 in Chronic Pain Treatment
Key Insights
Contineum Therapeutics announced positive topline data from its Phase 1b trial of PIPE-791, demonstrating favorable safety and tolerability in 43 patients with chronic osteoarthritis pain (search) or chronic low back pain (search).
The LPA1 (search) receptor antagonist showed encouraging trends across multiple exploratory efficacy endpoints, with patients demonstrating numerically greater improvements in pain measures compared to placebo.
PIPE-791 was administered as a once-daily 10mg oral dose and represents a potential non-opioid treatment option for chronic pain (search) conditions.
Contineum Therapeutics has reported positive topline data from its exploratory Phase 1b trial of PIPE-791, a selective lysophosphatidic acid 1 (LPA1 (search)) receptor antagonist, for the treatment of chronic osteoarthritis pain (search) (COAP) and chronic low back pain (search) (CLBP). The randomized, double-blind, placebo-controlled crossover trial met its primary endpoint of demonstrating favorable safety and tolerability while showing encouraging trends across multiple exploratory efficacy measures.
Trial Design and Patient Population
The 4-week crossover trial enrolled 43 patients, including 23 with chronic osteoarthritis pain (search) and 20 with chronic low back pain (search). The study design incorporated a washout period prior to the first 4-week treatment period, after which patients immediately crossed over into a second 4-week treatment period without an intervening PIPE-791 washout. PIPE-791 was administered orally at 10mg once-daily throughout the study.
Safety and Tolerability Profile
The trial achieved its primary objective of assessing safety and tolerability, with PIPE-791 demonstrating an adverse event profile generally consistent with previous clinical trials. Most treatment-emergent adverse events were mild to moderate, with no serious adverse events reported. The most common treatment-emergent adverse events were headache (n=3) and fatigue (n=2). Importantly, no clinically meaningful changes in mean systolic or diastolic blood pressure or clinically-relevant orthostatic events were observed.
Efficacy Signals Across Multiple Endpoints
Pain intensity was evaluated using the 11-point Pain-Intensity Numerical Rating Scale (PI-NRS), analyzed as the change from baseline in weekly average of average daily pain. Patients treated with PIPE-791 generally demonstrated improvements from baseline in pain that were numerically greater than the placebo arm. Similar positive trends were observed when PI-NRS was evaluated as the weekly average of the worst level of daily pain.
Beyond the primary pain measures, exploratory efficacy endpoints included an assessment of clinical responders (defined as patients achieving ≥30% reduction from baseline in PI-NRS) and the Modified Knee Injury and Osteoarthritis Outcome Scale (KOOS). Results from these exploratory measures further supported the positive PI-NRS findings, providing additional evidence of potential therapeutic benefit.
Clinical Significance and Expert Perspective
Dr. Robert H. Dworkin, Professor of Anesthesiology and Perioperative Medicine and of Neurology at University of Rochester Medicine (search), emphasized the clinical significance of these findings: "Chronic pain (search) remains a very significant unmet medical need, particularly for patients seeking effective and safe non-opioid treatment options. The early signals observed with PIPE-791, including improvements in pain measures and responder rates, are encouraging. The novel LPA1 (search) activity targets underlying mechanisms of pain. These data provide compelling support for further clinical investigation."
Mechanism of Action and Therapeutic Rationale
Chronic pain (search) is often associated with neuropathic symptoms caused by aberrant signaling in the central nervous system. LPA1 (search) activation has been shown preclinically to contribute to persistent hypersensitivity through demyelination of nerve fibers, increased neuronal excitability and neuroinflammation. By selectively blocking LPA1, PIPE-791 has the potential to modulate the maladaptive changes in the central nervous system and reduce pain.
Development Outlook
Dr. Timothy Watkins, Chief Medical Officer and Head of Development at Contineum Therapeutics, noted that these results demonstrate PIPE-791's tolerability in the largest patient population and longest treatment duration studied to date. "We are pleased with these results, which showed consistent trends toward improvement across multiple exploratory efficacy endpoints evaluating chronic pain (search) that, in general, numerically outperformed placebo," Watkins stated. "We believe these findings, particularly the COAP data, provide evidence of preliminary efficacy that support further evaluation of PIPE-791 for the potential treatment of chronic pain, and we are contemplating next steps for further clinical development."
The positive results from this Phase 1b trial reinforce confidence in PIPE-791's profile and its potential relevance to the company's ongoing PROPEL-IPF trial, where the drug is being evaluated for idiopathic pulmonary fibrosis (search). Contineum Therapeutics is a clinical-stage biopharmaceutical company focused on developing novel, oral small molecule therapies for neuroscience, inflammation and immunology indications with significant unmet medical needs.