Background

Peyronie’s disease (PD) is a connective tissue disorder characterized by fibrous plaque formation on the tunica albuginea, leading to penile curvature. Around 8-10% of men are affected by PD, and many may also experience erectile dysfunction with it.

Surgery is considered the gold standard for correcting curvature in selected patients with stable-phase PD. Collagenase Clostridium histolyticum (CCH) injections offer a nonsurgical alternative, but withdrawal from the European market has limited treatment options.

Hyaluronic acid (HA) monotherapy has piqued interest due to its antifibrotic and regenerative properties, although results have been variable. More recently, researchers have investigated HA combined with collagenase, lyase, and lipase in other clinical settings.

Study Objective and Outcomes

• Researchers evaluated the efficacy and safety of fibrorestil, an intralesional formulation of HA and an enzymatic mixture of collagenase, lyase, and lipase, when added to daily tadalafil, penile modeling, and traction therapy in men with stable-phase PD.
• Primary outcome: Absolute and relative changes in curvature at week 28, with response defined as a reduction of at least 15°.
• Secondary outcomes:
  • Erectile function, assessed using the erectile function domain of the International Index of Erectile Function (IIEF-EF), including the proportion of patients who achieved a minimally clinically important difference (MCID).
  • PD-related quality of life assessed using the Peyronie’s Disease Questionnaire (PDQ), which measures physical symptoms, penile pain, and symptom bother.
  • Treatment satisfaction, assessed using a 5-point Likert scale ranging from "very dissatisfied" to "very satisfied."
• Safety outcomes: Incidence and severity of adverse events, including serious adverse events.

Methods

• Open-label, multicenter, randomized controlled pilot study.
  • 38 men aged 18 years or older with stable PD (defined by the researchers as at least 3 months without symptom progression), palpable plaque, and curve between 30 and 90 °.
• Group A - Experimental (19 men)
  • Participants received three intralesional fibrorestil treatment sessions, administered four weeks apart. Each session included plaque tunneling.
    • Plaque tunneling: needle-created channels within the plaque.
  • Daily oral tadalafil up to 5 mg once daily
  • Modeling exercises at least 5 times daily
  • Penile traction device for a minimum of 4 hours per day on the flaccid penis
    • Slowly increased traction time according to tolerance
  • Group B – Standard (19 men) – received the same conservative treatment without injections.
  • Curve measured at baseline and at week 28 using either patient photographs or in-office measurements, potentially introducing variability.

Key Results/Analysis

• Overall, the findings suggest that fibrorestil with plaque tunneling may improve PD curvature and symptom bother when added to conservative treatment.
  • However, the small sample size and adjusted results limit conclusions about efficacy.
• Four participants were lost to follow-up (2 per group), leaving 17 men per group.

Primary Outcomes

• Group A demonstrated a statistically significant reduction in penile curvature.
  • Median absolute reduction: 15°.
  • Median relative reduction: 27.3%
• Group B: No median change in curvature.
• Responder rates were 52.9% (9/17) in Group A and 0% (0/17 men) in Group B.
• Despite greater baseline curvature in Group A, both groups had comparable curvature at week 28.
• Curvature improvement remained statistically significant after adjusting for baseline curvature.
• However, the difference was no longer significant after adjusting for additional clinical factors.
  • Without a placebo injection or tunneling-only group, the effects of fibrorestil cannot be separated from those of plaque tunneling.

Secondary Outcomes

• PDQ symptom bother improved significantly in Group A, suggesting a potential benefit for patients' experience of PD symptoms.
• Median IIEF-EF scores improved by 2 points in Group A and declined by 1 point in Group B. 
  • Clinically meaningful improvement occurred in 57.1% of Group A versus 33.3% of Group B.
  • Neither difference was statistically significant, limiting evidence of erectile function benefits.
  • Follow-up data were available for only 7 patients in Group B, further limiting comparisons.
• Treatment satisfaction was significantly higher in Group A (70.6% vs. 11.8%).
  • This suggests greater perceived benefit, although the open-label design may have influenced responses.
• Mild adverse events occurred in 36.8% (7/19) of Group A versus 5.3% (1/19) of Group B.
  • Group A reported penile bruising, injection-site pain, and swelling.
  • Group B reported tadalafil-associated back pain.
  • No participants discontinued due to adverse events, suggesting acceptable short-term tolerability, despite a small sample size.
• Longer traction use was associated with higher responder rates in Group A. 
  • This suggests adherence may influence treatment outcomes. 
  • Neither group met the prescribed four-hour daily minimum.
  • Researchers recommend devices that require a shorter amount of use per day.

Limitations

• The small, exclusively Spanish sample limits reliability and generalizability of the findings.
• The open-label design may have influenced patient-reported outcomes, particularly treatment satisfaction, as participants and researchers knew which treatment was administered.

Key Takeaways

• Intralesional fibrorestil with plaque tunneling was associated with improved PD curvature, symptom bother, and satisfaction, compared with conservative care in stable-phase PD patients.
• Although the experimental group demonstrated greater unadjusted curvature improvement, the effect was no longer statistically significant after adjustment for clinical factors.
• Larger, adequately controlled studies are needed to determine whether benefits are attributable to fibrorestil, plaque tunneling, or both, and to establish long-term efficacy and safety.

Resources

• Fernández-Pascual, E., Maiolino, G., Palma-Hendges, L. P., de la Morena, C. S., Solano-Heranz, P., Martínez-Piñeiro, L., Lledó–García, E., & Martínez-Salamanca, J. I. (2026). Efficacy and safety of hyaluronic acid and enzymatic mix intralesional therapy in Peyronie’s disease: A prospective, randomized, controlled pilot study of outcomes and patient satisfaction. The Journal of Sexual Medicine, 23(9). Oxford Academic. https://doi.org/10.1093/jsxmed/qdag278