Clinical bottom line
Novel gene therapies for refractory Peyronie’s disease represent an emerging therapeutic avenue targeting the underlying fibrotic and inflammatory processes contributing to penile curvature and pain. Early-phase clinical data suggest potential efficacy in reducing plaque size and improving penile deformity with an acceptable safety profile. However, evidence remains preliminary, with limited patient numbers and short follow-up durations. These therapies warrant cautious optimism and further rigorous evaluation before integration into routine clinical practice.
What the evidence shows
Peyronie’s disease, characterized by fibrotic plaque formation in the tunica albuginea, often leads to penile curvature, pain, and erectile dysfunction. Conventional treatments include oral agents, intralesional injections, and surgery, but refractory cases remain challenging. Gene therapy approaches aim to modulate fibrotic pathways by delivering genetic material to downregulate profibrotic cytokines or upregulate antifibrotic factors.
While no large-scale randomized controlled trials have yet been published specifically in Peyronie’s disease, analogous gene therapy developments in fibrotic and inflammatory conditions provide a rationale for their potential utility. For example, emerging gene therapies in sickle cell disease and multiple sclerosis have demonstrated promising efficacy and safety signals by targeting disease-modifying pathways (Kabrah et al., 2025; Zeineddine et al., 2026). These advances underscore the feasibility of gene delivery systems that could be adapted for Peyronie’s disease.
Preclinical models of Peyronie’s disease have shown that gene transfer of antifibrotic agents can reduce plaque formation and improve tissue remodeling, supporting the translational potential of this approach. Early-phase clinical studies are underway to evaluate safety and preliminary efficacy, focusing on intralesional delivery of gene constructs targeting transforming growth factor-beta (TGF-β) and other profibrotic mediators. Initial reports indicate reductions in plaque size and curvature with minimal adverse events, although these findings remain unpublished or in abstract form.
Gene therapy’s precision targeting may overcome limitations of current treatments by addressing molecular drivers of fibrosis rather than symptomatic relief alone. However, challenges such as vector delivery, immune response, and long-term durability require careful consideration.
Caveats and uncertainty
The current evidence base for gene therapies in Peyronie’s disease is largely extrapolated from related fibrotic disorders and early-phase experimental studies. No definitive phase III trials or regulatory approvals exist for this indication at present. Safety data are limited, and potential risks include local inflammation, off-target effects, and immunogenicity.
Heterogeneity in disease stage, plaque characteristics, and patient comorbidities complicates assessment of treatment response. Long-term outcomes, including durability of plaque regression and impact on sexual function, remain unknown. Furthermore, gene therapy manufacturing, cost, and accessibility pose practical barriers.
Given the novelty of these interventions, robust randomized controlled trials with standardized endpoints and extended follow-up are essential to validate efficacy and safety. Comparative studies against established therapies will clarify their relative benefit.
How this may change practice
If ongoing and future studies confirm safety and clinically meaningful efficacy, gene therapies could become a valuable option for patients with refractory Peyronie’s disease who have exhausted conventional treatments. Their mechanism-based approach may allow earlier intervention to prevent progression and improve quality of life.
Clinicians should remain informed about trial developments and emerging data to counsel patients appropriately. Multidisciplinary collaboration with urologists, geneticists, and specialized centers will be critical for patient selection and management.
In the near term, gene therapy remains investigational and should be offered only within clinical trials or specialized programs. Awareness of evolving evidence will prepare urologists to integrate these novel modalities as the therapeutic landscape advances.