Collagenase Clostridium Histolyticum

[Pantablo]

Xiaflex (COLLAGENASE CLOSTRIDIUM HISTOLYTICUM) has been introduced for the treatment of Dupuytren’s Contracture. Is anyone contemplating prior authorization critieria for this injectable medication. I suspect the drug will largely be administered in a physician's (orthopedic or hand surgeon's office). What concerns might people have about unrestricted access for this drug? The AWP is approximately $4000 per 0.9mg injection.

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[chantell.reagan]

Xiaflex (collagenase clostridium histolyticum) was recently approved by the FDA in February 2010 for the treatment of adult patients with Dupuytren's contracture with a palpable cord.

What is Dupuytren's contracture and what are the treatments?

It is an “uncommon hand deformity” whereby the connective tissue under the palm of the hand contracts and hardens/toughens over time. Grade 1 (mild) disease may not require treatment, but steroids are often helpful. Surgery is recommended with functional impairment, progression of contracture or with disabling deformity. If the MCP joint contracture reaches 30 degrees or if PIP joint contracture occurs at any degree, referral to a surgeon is warranted. Typically surgery is performed when the MCP joint contracture > 40 degrees or when the PIP joint contracture > 20 degrees. Of note, PIP joint contractures are more likely to cause stiffness and less likely to respond to surgery if more severe. Needle aponeurotomy of the nodule is an alternative to surgery. Xiaflex represents the first non-surgical biologic treatment approved by the FDA.

What is the incidence of Dupuytren's contracture?
The incidence is highest in Caucasians (particularly in those of Northern European descent), with a global prevalence of 3-6% (of the Caucasian population). Most cases occur in patients older >40yo, with 40% experiencing a hereditary component. Additionally Dupuytren's contracture is more common in men and there has been a link to increased incidence in diabetics.

How efficacious and safe is the drug?
To enter either of the two placebo-controlled clinical trials, participants had a palpable cord of at least 1 finger of 20-100 degrees in an MP joint or 20-80 degrees in a PIP joint AND a positive “table-top test” (defined as the inability to simultaneously place the affected fingers/palm flat on a table). Additionally patients could not have had surgery on the selected primary joint at least 90 days prior to the start of the trial. Xiaflex met its primary endpoint of reduction in contracture of selected primary joint to within 0-5 degrees of normal (after up to 3 injections). Approximately 27-39% of the patient population met the primary endpoint after the first injection (note the PI does not distinguish MP vs. PIP). Overall 44-64% of patients met the endpoint after up to 3 injections (MP 65-77% vs. PIP 28-40%). Xiaflex-treated patients also experienced a greater increase in range of motion.

According to the PI, serious rare adverse effects such as tendon rupture occurred in 0.03% of the patients. The most common ADRs occurring in ≥25% were peripheral edema, contusion, injection site reaction/hemorrhage, pain in the injected extremity. It must also be used in caution in patients with coagulation issues or being treated with anticoagulants.

How often is Xiaflex administered and who can administer/supply it?
According to the PI, injections and finger extension procedures may be administered up to 3 times per cord, at approximately 4 week intervals. Only 1 cord may be injected at a time, as the effect of multiple simultaneous doses is unknown, and could cause localized or severe reactions (i.e. tendon rupture). If contracture remains at the 24 hour follow-up, physicians should perform a passive finger extension to facilitate cord disruption.

Physicians, who are typically hand surgeons/specialists or orthopedists, must be enrolled and trained in the Xiaflex Xperience Program to administer the drug. Additionally the Managed Distribution Network Partners include Besse Medical, Curascript Specialty Distribution, McKesson Specialty Care Solutions, Accredo Health, BioScrip, CVS/Caremark Specialty Pharmacy, Curascript Specialty Pharmacy, Aetna Specialty and Integrated Commercialization Solutions dba XIAFLEXDirect. Of note the vial must be refrigerated prior to reconstitution.

Is Xiaflex being studied in any other disease states?
Of note, Xiaflex is currently being studied in phase II for Peyronie’s disease and frozen sholder syndrome, both also connective tissue disorders.

Bottom line
As Xiaflex is the first pharmacologic product FDA approved for Dupuytren's contracture, it is unclear how it will best fit into the treatment algorithm of the disease. There are many factors to consider including: type of joint(s) affected, severity of disease (i.e. disabling, etc), surgical candidate and/or rfailure of surgery. As the overall incidence of this disease is small, the percentage of patients receiving actual benefit from the drug may be even smaller.

Additional sources:
Xiaflex prescribing information
Trojian TH and SM Chu. Am Fam Physician. 2007 Jul 1;76(1):86-9.
Hurst LC et al. N Engl J Med. 2009 Sep 3;361(10):968-79.
Mayo Clinic: Dupuytren's contracture
Auxilium: Dupuytren's contracture
FierceBiotech news 4/09

[chantell.reagan]

We received this comment from one of our members:

"Maybe this relates to the issue of whether or not prior auth is warranted, but let's not forget that this is for Dupuytren's contracture WITH a palpable cord. All of the contractures first start as a nodule. However, this nodule is not collagen-deposited; therefore any earlier use (than when palpable cord is present) would not be effective as the product only works against its specific collagen types. Plus there are risks associated with use in that these are the same collagen types that compose tendons."

[powellwow]

We are evaulating whether coverage criteria will be necessary. The manufacturer's representative told me that the REMS program will prevent off-label use. However, I have not had an opportunity to verify that myself in the details of the REMS program yet.

[diana.papshev]

Anonymous feedback:

"We will allow utilization for not only orthopedics and hand surgeons, but also physicians who have been trained and certified to administer this treatment."

[diana.papshev]

Anonymous feedback:

"I suspect that reimbursement issues are a moot point. That's because it's likely that most health plans and other 3rd party payers will consider Xiaflex to be either experimental and/or investigational or not medically necessary. Despite FDA approval, long-term data on safety and effectiveness are lacking. In addition, there are alternative therapies that are well-established and accepted."

[diana.papshev]

Anonymous feedback:

"What is the cost of the surgical procedure this avoids? From the clinical presentation description, it sounded pretty complex, and I’m sure it’s not inexpensive"

[chantell.reagan]

Anonymous feedback:

"Variable but professional fee about $1-2000, and hospital $5000-7500"

[chantell.reagan]

Anonymous response:

1. The CPT code is 26123 (Fasciectomy,palmar with release of a single digit. . .) Medicare fees depending on the region run from $593 to $1064 according to the CMS look-up.
2. If this is done in the HOPD, then it is likely to be paid as an APC in the range of $2000. Generally this includes all supplies.
3. Anesthesia may be in the range of $500 unless the surgeon does the procedure under a regional block , then the cost of the block is included in the surgical code.
4. The patient may need some hand therapy afterwards for stretching. Let’s say 3x a week for 4 weeks at $80 per treatment. That is about $960.

Adding it all up the cost can range from about $2600 on the low side to just over $4500 on the high side.