First-in-Class Oral Piclidenoson Reaches Pivotal Phase 3 Enrollment Milestone in Plaque Psoriasis

Can-Fite BioPharma has completed enrollment of the first 247 patients required for the planned interim analysis of its pivotal phase 3 trial (NCT06643260) evaluating piclidenoson, a first-in-class oral A3 adenosine receptor (A3AR) agonist, in adults with moderate-to-severe plaque psoriasis. If approved, piclidenoson would become the first therapy targeting the A3AR pathway for plaque psoriasis, offering a novel oral treatment option within an increasingly competitive therapeutic landscape. efficacy and safety results are expected in the fourth quarter of 2026 or the first quarter of 2027.¹³

Unlike currently available biologics and targeted oral therapies, piclidenoson selectively targets the A3 adenosine receptor, a novel anti-inflammatory pathway under investigation for chronic plaque psoriasis.¹

Phase 3 Trial Design

The randomized, double-blind, placebo-controlled phase 3 study (NCT06643260) is being conducted under a protocol agreed upon with both the US Food and Drug Administration (FDA) and the European Medicines Agency (EMA), providing a potential regulatory pathway for future marketing applications in both regions.¹

The multicenter study is expected to enroll approximately 705 participants and is evaluating piclidenoson 3 mg administered orally twice daily versus placebo in adults with moderate-to-severe plaque psoriasis. Enrollment will continue while investigators conduct the planned interim efficacy and safety analysis of the first 247 enrolled patients. The interim analysis will evaluate efficacy and safety while enrollment continues toward the study's planned enrollment target.

The co-primary efficacy end points are the proportion of patients achieving Psoriasis Area and Severity Index 75 (PASI 75) and Static Physician's Global Assessment (sPGA) scores of 0 or 1 at week 16.¹³

First-in-Class Oral A3 Adenosine Receptor Agonist

Piclidenoson is an orally bioavailable, selective A3 adenosine receptor (A3AR) agonist designed to target inflammatory pathways involved in psoriasis. Activation of the receptor inhibits the inflammatory cytokines IL-17 and IL-23 while promoting apoptosis of pathogenic keratinocytes implicated in psoriasis pathogenesis.¹

"We are pleased to achieve this important enrolment milestone in our pivotal Phase 3 psoriasis study," said Motti Farbstein, chief executive officer of Can-Fite, in a statement. "This study is being conducted under a protocol agreed with both the FDA and EMA, providing a clear regulatory pathway for Piclidenoson.”¹

Previous Clinical Evidence

The current study follows the phase 3 COMFORT-1 trial, which compared piclidenoson with placebo and apremilast. Although the trial was affected by elevated withdrawal rates associated with COVID-19 disruptions, investigators reported comparable efficacy between the 2-mg and 3-mg twice-daily doses and concluded the findings supported continued clinical development of piclidenoson.²

If the phase 3 program is successful, piclidenoson could become a novel oral systemic therapy available for moderate-to-severe plaque psoriasis, offering a mechanism distinct from biologics and Janus kinase inhibitors. The investigational therapy has demonstrated a favorable safety profile in more than 1,500 participants across clinical studies to date.¹

References

• Can-Fite achieves key pivotal phase 3 psoriasis milestone with completion of patient enrolment for the interim analysis: data expected Q4 2026/Q1 2027. News release. Can-Fite BioPharma.
• Papp, K. A., Beyska-Rizova, S., Gantcheva, et al. & COMFORT‚Äê1 Study Investigators (2024). Efficacy and safety of piclidenoson in plaque psoriasis: Results from a randomized phase 3 clinical trial (COMFORT-1). Journal of the European Academy of Dermatology and Venereology : JEADV, 38(6), 1112-1120. https://doi.org/10.1111/jdv.19811
• ClinicalTrials.gov. A Phase 3, Randomized, Double-Blind, Placebo-Controlled Study of the Efficacy and Safety of Daily Piclidenoson (CF101) Administered Orally in Subjects With Moderate-to-Severe Plaque Psoriasis (NCT06643260). https://clinicaltrials.gov/study/NCT06643260