Who is paying for xiaflex in Peyronie's?

2 Penile Injections ( XIAFLEX® ) COST: 2 vials $2,650

Injecting a drug right into the plaque brings higher doses of the drug to the problem than when a drug is taken by mouth. Plaque injection is often used for men with acute phase disease who aren't sure they want to have surgery. The skin is often numbed before the shot to reduce pain.

Injection of CCG into collagen-containing structures such as the corpora cavernosa of the penis may result in damage to those structures and possible injury such as corporal rupture. Treatment of Peyronie's disease with intralesional therapy: Injection of collagenase is contraindicated in the treatment of Peyronie’s plaques that involve the penile urethra due to potential risk to this structure and in patients with a history of hypersensitivity to collagenase used in any other therapeutic application or application method. Injection of collagenase into collagen-containing structures such as the corpora cavernosa of the penis may result in damage to those structures and possible injury such as corporal rupture (penile fracture).

https://www.fda.gov/downloads/Drugs/DrugSafety/UCM200615.pdf

 

Xiaflex (Collagenase) for use in Peyronie's Disease
Understanding Peyronie's Disease and Collagenase as a Treatment

Auxilium pharmaceuticals developed a “highly purified” enzyme to dissolve this abnormal scar tissue called collagenase. It is produced by bacteria (prior versions were taken from animals), and it is the same enzyme responsible for tissue destruction when a person gets gangrene. Therefore, the dosage administered into penile scar tissue is minuscule (less than 1 mg) but can still have a strong effect.

Auxilium had hundreds of men in their phase 3 clinical trial conducted at multiple urologist offices across the USA and in other countries. All men had to receive approximately 15-20 penile injections over the course of a year. Some injections were to artificially induce erections for the doctor so progress could be measured (and then another injection to cause the artificial erection to go down). The drug itself was injected 8 times, over the course of 8 visits. All patients had to visit the office between 15-20 times to determine eligibility and to perform measurements of drug efficacy. Patients were compensated around $500 (in total) for all visits, including the men who received the placebo (and thus, no benefit). One third of study participants received the placebo, and the remainder received the active drug. People who received the placebo improved by 18% whereas people who received the drug improved by 34%. “Improvement” was measured as the amount to which the curve of the penis was reduced. Data on overall penile length and reduction of narrowing were not reported by the drug company, despite the fact that data on penile length was collected and is a significant cause of concern for Peyronie’s patients.
There are many concerns with this drug, and there are many falsehoods that are out there about how it works and exactly who got this 34% benefit. In general, Auxilium excluded any patient that had a complex case of Peyronie’s (no patients with a narrowing deformity called “hourglassing” and no patients who had calcium in their plaques were allowed in the study). Some think that this was done so that Auxilium could inflate how well patients responded to the drug and get FDA approval more easily. No single men or gay men were allowed in the study. It has been speculated that this was due to Auxilium’s worry that single men or gay men would put the drug in the “cosmetic” category in the eyes insurance companies, the most likely payor for these injections (which are $3000-5000 each). The real reasoning is not publicly known.

1. The Auxilium version of collagenase is selective for scar tissue only. It will not dissolve blood vessels. It will only dissolve scar tissue.
False. Dissolving capillaries causes blood to overflow into the skin, forming sacs filled with dark blood. This happens within hours of injection, and it can lead to permanent scarring once the blistered skin peels off. What collagenase does cannot be repaired by one's own bodily processes until much later.

2. The collagenase molecule, once injected, will be able to “move through” the plaque and dissolve it. False. Collagenase (as a molecule) is huge and collagen molecules are huge. Injecting a tiny amount of collagenase into a collagen plaque in Peyronie’s disease will only dissolve the scar tissue in a tiny area around the injection site. The collagenase molecule simply is not able to move through a collagen plaque due to the size of the molecules. Once the enzyme (collagenase) binds to its substrate (collagen), it doesn’t “keep going” very far. That's why it takes 8 injections for a 34% improvement.

3. Collagenase is the enzyme responsible for tissue destruction in gangrene.
True. You are essentially causing gangrene of your own penis by allowing yourself to be injected with collagenase. It’s a “controlled” gangrene – but it is the same enzyme. It is isolated from bacteria, not animal sources. It is no different than botox in this regard, which is considered safe. However, botox has far fewer side effects to achieve the drug benefit.

4. Collagenase does nothing to restore elastin, which has also been destroyed by Peyronie’s disease plaques.
True. In lucky patients, it will dissolve some collagen scar tissue. However, the elastin that existed in the tunica albuginea before the disorder started is certainly not restored by an enzyme that destroys collagen. Some people whose scar plaques go away naturally still have curvature because of the damage caused by Peyronie's in general.

5. Hourglass deformities (localized narrowing) of the penile shaft can be treated by collagenase.
Unknown. Auxilium refused to enroll people with hourglass deformities in the study, possibly so that they would have more positive results in the end. There is no way to know if an hourglass deformity will be helped by collagenase. However, once the drug is approved for Peyronie’s disease, it may be used for hourglass deformities by patients with no other options (TBD).

6. The best way to inject collagenase is in a line perpendicular to the penis, directly into the scar tissue (which was done in the trial).
Unknown. All patients are different. Also, collagenase will not go very far beyond the area where it is injected into. So, a perpendicular line may only result in a mild benefit IF the plaque happens to be susceptible to injections made in that pattern. Injecting the substance vertically would risk needle injury to the neurovascular bundle in a dorsal plaque. However, multiple small injections or diagonal injections may be more beneficial. No known research was done to determine the injection technique.

7. All patients should receive the same dose of collagenase, regardless of plaque size or penis size. These doses are uniformly supplied in powder form to the physician.
True to Auxilium - but logically, it makes no sense. Why would you give the same dose to a man with a large penis and large plaque vs. a man with a small penis and small plaque? As packaged and tested in Phase 3, all patients get the same dose. Once the powdered collagenase is mixed with saline for injection, it has extremely limited storage life, so it cannot be split among patients or injected on separate occasions. Each powdered vial dose is approx. $4000.

8. Collagenase can dissolve scar tissue in the penile septum.
False (most likely). The penile septum cannot be injected due to severe risk of injury to the corporal bodies adjacent to this area. Collagenase will not “drip down” into the septum since the molecule is too big to move past the area where it is directly injected into. Almost all patients with peyronie’s disease have scar tissue in the septum (based on in vitro tissue sample analysis post operatively).

9. Collagenase can help men with calcified penile plaques.
Unknown. Auxilium excluded men with calcified plaques from participating in the study.

10. Auxilium has quantified how well their drug works on plaque.
False. Auxilium has never measured precisely how well the drug dissolves the scar tissue with any quantitative method. They are only (potentially) looking into this now – way after the drug has already been tested on human beings.

 

In 2019, Can PRP and Penile Traction Device Replace Collagenase to Treat Peyronie's Disease?

Peyronie's disease (PD) is an accumulation of collagen in the penis that creates a scar, producing a deformity and pain in the erectile state, that affects between 1%-8% of men. ANDROMEDICAL laboratory proposes a new strategy to treat PD based on combined therapy of platelet-rich fibrin matrix (PRFM or activated-PRP) with Andropeyronie, a penile traction device (PTD) designed to treat penile curvatures. Now urologists, their patients and health insurance companies may have a cost-effective alternative to collagenase and surgery for effectively treating Peyronie's disease, without side effects of other therapies.

In 2013 the US-FDA approved the use of collagenase (CCH) for its treatment. Collagenase is an enzyme that breaks the peptide bonds of collagen, but medical studies showed that effectiveness was limited to a 33% correction of penile curvature. In 2013, Dr. Martínez-Salamanca (Spain) carried out a hospital study with the penile traction device called PTT to treat Peyronie's disease in the acute phase, achieving a 60% correction of the curvature. In 2015 the American Urological Association recommends treating Peyronie's disease with combined collagenase therapy and Peyronie's plaque remodeling, done with manual exercises or with a soft progressive force for a few hours a day with a penile traction device (PTD).

In 2018 Dr. Terlecki (USA) published a clinical study on the use of autologous platelet-rich plasma (PRP) in Peyronie's disease whose conclusions were that the activated-PRP or PRFM appears to be a safe and feasible treatment, more than 80% of patients improved in their degree of curvature. Evidence suggests that platelets play an important role in tissue repair, vascular remodeling and inflammatory and immune responses through secretion of growth factors, cytokines and chemokines. Thus, injection of PRFM could combine mechanical disruption of the plaque, via needle fracture, while simultaneously neutralizing destructive inflammatory processes in an effort to promote a better wound-healing response and stabilize the disrupted plaque. It is important to note that collagenase injection does not address appropriate wound healing or regeneration of the damaged tissue.

In 2013 Dr. Chung (Australia) demonstrated that penile traction translates mechanical stimuli into a chemical response leading to activation of cell proliferation. In 2019 Dr. Romero (Spain) published a clinical study demonstrating that the use of a penile traction device reduces the need of cycles of collagenase in patients with Peyronie's disease.

The world of urology is advancing rapidly and clinics are beginning to use this promising combined therapy of platelet rich plasma with penile traction therapy in hopes of wound healing and tissue regeneration. New treatment options for Peyronie's disease are opening up, with benefits for patients, urologists and health insurance companies. Therapy of PRP with PTD is an effective treatment without side effects, easily performed in the doctor's office and a cost-effective alternative to other therapies.