What is Intralesional Collagenase Clostridium Histolyticum?
Intralesional collagenase clostridium histolyticum (CCH) is an FDA-approved enzymatic injection therapy that breaks down collagen in fibrous plaques to reduce penile curvature in men with stable Peyronie's disease. 1
Mechanism of Action
Collagenase clostridium histolyticum is a mixture of two bacterial collagenases (AUX-I and AUX-II) derived from Clostridium histolyticum fermentation that specifically degrades types I, II, and III collagen in the abnormal fibrous plaques of Peyronie's disease. 2, 3 The enzyme works by enzymatically breaking down the interstitial collagen that forms the rigid, non-compliant scar tissue in the tunica albuginea of the penis. 4
FDA-Approved Indications & Patient Selection
CCH is indicated for adult men with stable Peyronie's disease who have penile curvature >30° and <90°, with intact erectile function (with or without medications). 1 The treatment specifically addresses curvature deformity—it does not treat penile pain or erectile dysfunction as primary outcomes. 1
Key eligibility criteria from the pivotal IMPRESS trials:
- Stable disease (no progression for at least 3 months) 1
- Curvature between 30° and 90° 1
- Preserved erectile rigidity sufficient for intercourse 1
Treatment Protocol
The FDA-approved protocol involves:
- Up to 8 injections of 0.58 mg (10,000 units) over 24 weeks 1
- Two injections per treatment cycle, separated by 24-72 hours 1
- Four treatment cycles total, each separated by 6 weeks 1
- Mandatory penile modeling by the clinician after each cycle 1
- Patient-performed home modeling 3 times daily between cycles 1
- Daily attempts to straighten the penis during spontaneous erections 1
The modeling component is critical—it is not optional and appears essential to achieving optimal outcomes. 1
Clinical Efficacy
In the IMPRESS I and II trials with one-year follow-up:
- Mean curvature reduction: 17° in CCH groups vs 9.3° in placebo groups 1
- Net benefit: 7.7° difference (this is modest but statistically significant) 1
- Median percent improvement: 33-45% depending on compliance 5, 6
Compliance significantly impacts outcomes—patients completing the full protocol achieve greater curvature reduction (median 44.4% vs 33.3% in non-compliant patients). 5 The overall compliance rate is approximately 71%, with common reasons for discontinuation including adverse effects (15%), early satisfaction (14%), and unknown factors (45%). 5
Expanded Applications Beyond Original Trials
Recent evidence demonstrates CCH efficacy in populations excluded from the pivotal trials:
- Ventral curvatures: Median improvement of 25° (44.7% reduction), comparable to non-ventral curvatures 6
- Calcified plaques: Significant improvement of 17.5° regardless of calcification type 7
- Acute-phase disease: Preliminary studies suggest CCH may modify disease progression even before stabilization 3, 8
Notably, no urethral injuries occurred in the ventral curvature cohort, addressing a theoretical safety concern. 6
Adverse Events & Safety Profile
Patients must be counseled about high rates of treatment-related adverse events, though most are mild-to-moderate and self-resolving. 1
Common adverse events from IMPRESS trials:
- 84.2% of CCH patients experienced at least one adverse event (vs 36.3% placebo) 1
- Penile ecchymosis (bruising): most common 1, 2
- Penile swelling and pain 1, 2
- Hematoma: 37-50% depending on curvature direction 6
Serious adverse event: corporal rupture (rare but documented—patients must be explicitly warned). 1 Most adverse events resolved without intervention. 1
The enzyme is not associated with penile length shortening, which distinguishes it from surgical plication procedures. 2
Current Guideline Status
The 2025 European Association of Urology guidelines note that CCH has been withdrawn from the European market, though it demonstrated effective pain control and curvature reduction when available. 9 The 2015 American Urological Association guidelines support its use as a moderate recommendation (Evidence Grade B) for appropriate candidates. 1
Combination Therapies
Emerging evidence suggests enhanced outcomes with adjunctive treatments:
- PDE5 inhibitors (sildenafil, tadalafil) combined with CCH appear superior to CCH alone for improving both curvature and erectile function 9, 4
- Penile traction therapy as adjunct showed average length increases of 1 cm 9
These combinations require further validation but show promise for optimizing non-surgical management. 9
Critical Pitfalls to Avoid
- Do not use CCH for pain management—it treats curvature, not pain. Use NSAIDs or tadalafil for active-phase pain. 9, 1
- Do not inject patients with active/unstable disease unless participating in research protocols—FDA approval is for stable disease only. 1
- Do not skip the modeling component—both clinician and patient modeling are integral to the protocol. 1
- Do not inject into dense or heavily calcified plaques without ultrasound assessment—though recent data shows benefit, local drug delivery may be impeded. 9, 7
- Avoid concurrent use of metal ion antiseptics or acidic solutions—these inhibit enzyme activity. 10
Comparison to Alternatives
CCH occupies a middle ground between ineffective oral therapies and definitive surgery:
- Oral agents (vitamin E, tamoxifen, pentoxifylline) are not recommended due to lack of efficacy and potential to delay effective treatment 9, 11
- Surgery remains the gold standard for severe deformity or CCH failure, requiring 3-6 months of stable disease 9
- Penile traction therapy is safe and effective but requires 2-8 hours daily use 9
CCH provides a minimally invasive option for men who want to avoid surgery but need more than conservative management. 2, 8