Cigna Drug and Biologic Policy

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1 Cigna Drug and Biologic Policy Subject Collagenase clostridium histolyticum Effective Date... 11/15/2017 Next Review Date... 11/15/2018 Coverage Policy Number Table of Contents Coverage Policy... 1 General Background... 3 Coding/Billing Information... 4 References... 4 Related Coverage Resources Male Sexual Dysfunction Treatment: Nonpharmacologic INSTRUCTIONS FOR USE The following Coverage Policy applies to health benefit plans administered by Cigna companies. Coverage Policies are intended to provide guidance in interpreting certain standard Cigna benefit plans. Please note, the terms of a customer s particular benefit plan document [Group Service Agreement, Evidence of Coverage, Certificate of Coverage, Summary Plan Description (SPD) or similar plan document] may differ significantly from the standard benefit plans upon which these Coverage Policies are based. For example, a customer s benefit plan document may contain a specific exclusion related to a topic addressed in a Coverage Policy. In the event of a conflict, a customer s benefit plan document always supersedes the information in the Coverage Policies. In the absence of a controlling federal or state coverage mandate, benefits are ultimately determined by the terms of the applicable benefit plan document. Coverage determinations in each specific instance require consideration of 1) the terms of the applicable benefit plan document in effect on the date of service; 2) any applicable laws/regulations; 3) any relevant collateral source materials including Coverage Policies and; 4) the specific facts of the particular situation. Coverage Policies relate exclusively to the administration of health benefit plans. Coverage Policies are not recommendations for treatment and should never be used as treatment guidelines. In certain markets, delegated vendor guidelines may be used to support medical necessity and other coverage determinations. Proprietary information of Cigna. Copyright 2017 Cigna Coverage Policy Cigna covers collagenase clostridium histolyticum (Xiaflex ) as medically necessary for the treatment of a symptomatic Dupuytren s contracture in adults for a maximum of 3 injections per cord as an alternative to surgical treatment when both of the following criteria are met: Presence of a palpable cord Functional impairment as manifested by a metacarpophalangeal (MCP) joint or proximal interphalangeal (PIP) joint contracture of 20 degrees of greater. Cigna covers collagenase clostridium histolyticum (Xiaflex ) as medically necessary for the treatment of Peyronie s disease in adult men for a maximum of 4 treatment cycles (or 8 injections) when all of the following are met: Presence of a palpable plaque Curvature deformity between 30 degrees and 90 degrees at the start of therapy Primary reason for treatment is one of the following: o Pain o Sexual dysfunction and coverage is available for the treatment of male sexual dysfunction* *Note: The treatment of male sexual dysfunction, including erectile dysfunction, is specifically excluded under many benefit plans, regardless of underlying condition; therefore, use of Xiaflex for Peyronie s disease, where the primary reason for treatment is sexual dysfunction, is generally not covered. Please refer to the applicable benefit plan document to determine benefit availability and the terms, conditions and limitations of coverage. Cigna does not cover the use of collagenase clostridium histolyticum (Xiaflex ) for any other indication because it is considered experimental, investigational or unproven. When coverage is available and medically necessary, the dosage, frequency, duration of therapy, and site of care should be reasonable, clinically appropriate, and supported by evidence-based literature Page 1 of 5

2 and adjusted based upon severity, alternative available treatments, and previous response to collagenase clostridium histolyticum (Xiaflex ) therapy. Note: Receipt of sample product does not satisfy any criteria requirements for coverage FDA Approved Indications Xiaflex is indicated for the treatment of adult patients with Dupuytren s contracture with a palpable cord. Xiaflex is indicated for the treatment of adult men with Peyronie s disease with a palpable plaque and curvature deformity of at least 30 degrees at the start of therapy. FDA Recommended Dosing Dupuytren s Contracture Xiaflex should be administered by a healthcare provider experienced in injection procedures of the hand and in the treatment of patients with Dupuytren s contracture. The dose of Xiaflex is 0.58 mg per injection into a palpable cord with a contracture of a metacarpophalangeal (MP) joint or a proximal interphalangeal (PIP) joint. Approximately 24 to 72 hours after injection, perform a finger extension procedure if a contracture persists to facilitate cord disruption. Four weeks after the Xiaflex injection and finger extension procedure, if a MP or PIP contracture remains, the cord may be re-injected with a single dose of 0.58 mg of Xiaflex and the finger extension procedure may be repeated (approximately 24 to 72 hours after injection). Injections and finger extension procedures may be administered up to 3 times per cord at approximately 4-week intervals. Perform up to two injections in the same hand during a treatment visit. Two palpable cords affecting two joints may be injected or one palpable cord affecting two joints in the same finger may be injected at two locations during a treatment visit. If a patient has other palpable cords with contractures of MP or PIP joints, these cords may be injected with Xiaflex at other treatment visits approximately 4 weeks apart. Each vial of Xiaflex should only be used for a single injection. If two joints on the same hand are to be treated during a treatment visit, separate Xiaflex vials should be used for each injection. Peyronie s Disease Xiaflex should be administered by a healthcare provider experienced in the treatment of male urological diseases, who has completed required training for use of Xiaflex in the treatment of Peyronie s disease. The dose of Xiaflex is 0.58 mg per injection administered into a Peyronie s plaque. If more than one plaque is present, inject into the plaque causing the curvature deformity. A treatment course consists of a maximum of 4 treatment cycles. Each treatment cycle consists of two Xiaflex injection procedures and one penile modeling procedure. The second Xiaflex injection procedure is performed 1 to 3 days after the first. The penile modeling procedure is performed 1 to 3 days after the second injection of the treatment cycle. The interval between treatment cycles is approximately six weeks. The treatment course therefore, consists of a maximum of 8 injection procedures and 4 modeling procedures. If the curvature deformity is less than 15 degrees after the first, second or third treatment cycle, or if the healthcare provider determines that further treatment is not clinically indicated, then the subsequent treatment cycles should not be administered. The safety of more than one treatment course of Xiaflex is not known. Drug Availability Xiaflex is supplied in single-use vials containing 0.9 mg of collagenase clostridium histolyticum Xiaflex Risk Evaluation and Mitigation Strategy (REMS) Program Because of the risks of corporal rupture (penile fracture) or other serious penile injury in the treatment of Peyronie s disease, Xiaflex is available only through the Xiaflex REMS Program. Required components of the Xiaflex REMS Program include the following: o Prescribers must be certified with the program by enrolling and completing training in the administration of Xiaflex treatment for Peyronie s disease. Page 2 of 5

3 o Healthcare sites must be certified with the program and ensure that Xiaflex is only dispensed for use by certified prescribers. General Background Pharmacology Xiaflex contains two collagenases, AUX-I and AUX II, which are isolated from fermentation products of Clostridium histolyticum bacteria. The cords formed in Dupuytren contracture and the plaque that develops in Peyronie s disease are made of collagen, which make them susceptible to collagenase. (McEvoy, 2017) Guidelines The Peyronie s Disease Panel, of the American Urological Association (AUA), addresses Xiaflex treatment in recently published guidelines. In individuals with stable Peyronie s disease (PD), and penile curvature of > 30 and < 90, the PD panel gives a moderate recommendation (based on moderate curvature reduction in the setting of low risk of serious adverse events) to use of Xiaflex in conjunction with modeling, by both physician and patient, to achieve reduced penile curvature. The guidelines state that use of Xiaflex is inappropriate in individuals whose sole concern is pain and/or erectile dysfunction. The panel suggests the risks versus benefits of Xiaflex use should be carefully weighed, and remark that Xiaflex achieved modest results when compared to placebo. The AUA recognizes a current lack of evidence for use of Xiaflex in individuals with various other abnormalities or deformities, therefore, outcomes in these circumstances are unknown. (Nehra, 2015) Clinical Efficacy Dupuytren s Contracture No trials comparing Xiaflex to other treatments or to surgery have been reported. There are no data evaluating Xiaflex for surgery prevention. In three randomized, double-blind trials involving a total of 409 adults with Dupuytren disease with MCP or PIP contracture of 20 in at least one finger, more patients evaluated 30 days after the last of up to three treatments achieved a reduction in joint contracture to within five degrees of normal with Xiaflex 0.58 mg (44.4% to 91%) compared with placebo (0% to 6.8%, p < 0.001) (Hurst., 2009; Badalamente, 2007; Center for Drug Evaluation and Research, 2010; Auxilium, 2016). In the largest trial, the median time to reach the primary endpoint was 56 days. In two trials, more patients achieved > 50% improvement from baseline in the primary contracture with Xiaflex (77.8% to 84.7%) compared to placebo (11.7% to 14.3%, p < 0.001). In one unpublished, long-term follow-up study, the nominal 2-year recurrence rate was 19.3% (119/619 joints). An evaluation of the safety and efficacy of 2 concurrent injections of Xiaflex (followed by a finger extension procedure 24 to 72 or more hours later) for multiple Dupuytren contractures in the same hand was conducted in two separate studies. In the first study, a total of 60 patients were enrolled in an open-label, phase IIIb study. The majority of patients (47%) received treatment of the MCP and PIP joints on the same finger and 37% received treatment of MCP joints on different fingers. A mean reduction in total flexion contracture was 76%. Patients who had received prior treatment of any joint had a lower mean reduction in total flexion contracture of 70% compared with those who had no prior treatment at 80%. Three serious adverse events were reported including a hospitalization for hand pain post-injection, a pulley rupture, and a flexor tendon rupture. (Coleman, 2014) The second study enrolled 715 patients in an open label, phase IIIb study. Thirty one days after receiving two Xiaflex injections in the same hand during a single visit, flexion contractures decreased 74% and mean total range of motion increased from 90 to 156. Adverse events were mild to moderate in nature and resolved without intervention. (Gaston, 2015) Peyronie s Disease IMPRESS I and II were identical, randomized, double-blind, phase 3 clinical trials evaluating the safety and efficacy of Xiaflex compared to placebo for Peyronie s disease (PD). Patients were included in the trial if they had a diagnosis of PD for 12 months and were determined to be stable with penile curvature of at least 30 degrees but less than 90 degrees. The first primary endpoint was the mean improvement in penile curvature at 52 weeks. For IMPRESS I, Xiaflex-treated patients had a 37.6% mean improvement compared with placebotreated patients who had a 21.3% improvement (p = ). For IMPRESS II, Xiaflex-treated patients had a 30.5% mean improvement versus the placebo-treated patients with a 15.2% improvement (p = ). For the second primary endpoint of mean improvement in the PD symptom bother domain score, Xiaflex-treated patients in both IMPRESS trials had a statistically significant improvement compared to placebo-treated Page 3 of 5

4 patients. Six serious adverse events occurred, including 3 cases of corporeal rupture requiring surgical repair and 3 cases of penile hematoma. (Gelbard, 2013) Coding/Billing Information Covered when medically necessary: HCPCS J0775 Description Injection, collagenase clostridium histolyticum, 0.01 mg Covered when medically necessary when used for the treatment of a symptomatic Dupuytren s contracture in adults: CPT * Description Injection, enzyme (e.g., collagenase), palmar fascial cord, (i.e., Dupuytren s contracture) Manipulation, palmar fascial cord (i.e., Dupuytren s cord), post enzyme injection (e.g., collagenase), single cord Application of finger splint; static If coverage for the treatment of male sexual dysfunction, including erectile dysfunction, is available under the specific health benefit plan, the following may be covered when medically necessary: CPT * Description Injection procedure for Peyronie disease; Injection of corpora cavernosa with pharmacologic agent(s) (eg, papaverine, phentolamine) *Current Procedural Terminology (CPT ) 2017 American Medical Association: Chicago, IL. References 1. Auxilium Pharmaceuticals, Inc. Xiaflex (collagenase clostridium histolyticum) for injection, for intralesional use [product information]. Chesterbrook, PA: Auxilium Pharmaceuticals, Inc. August Badalamente M, Hurst L. Efficacy and safety of injectable mixed collagenase subtypes in the treatment of Dupuytren's contracture.j Hand Surg Am Jul-Aug;32(6): Center for Drug Evaluation and Research. Medical Review(s) Application number: Food and Drug Administration. Department of Health and Human Services. Accessed Sep 25, Available at URL address: 4. Coleman S, Gilpin, D, Kaplan FTD, et al. Efficacy and safety of concurrent collagenase clostridium histolyticum injections for multiple Dupuytren contractures. J Hand Surg Am 2014; 39 (1): Gaston R, et al. The Efficacy and Safety of Concurrent Collagenase Clostridium Histolyticum Injections for 2 Dupuytren Contractures in the Same Hand: A Prospective, Multicenter Study. J Hand Surg AM 2015; 40 (10) Gelbard M, Goldstein I, Hellstron WJG, et al. Clinical efficacy, safety and tolerability of collagenase clostridium histolyticum for the treatment of Peyronie disease in 2 large double-blind, randomized, placebo controlled phase 3 studies. J Urol 2013; 190: Hurst LC, Badalamente MA, Hentz VR, et al. Injectable collagenase clostridium histolyticum for Dupuytren s contracture. N Engl J Med. Sep ;361(10): Page 4 of 5

5 8. McEvoy GK, Pharm.D., ed AHFS Drug Information - 59th Ed. Bethesda, MD. American Society of Health-System Pharmacists. 9. Nehra A, Alterowitz R, Culkin D, et al. Peyronie s Disease: AUA Guidelines. J Urol Jun 9. pii: S (15) doi: /j.juro [Epub ahead of print] The registered marks "Cigna" and the "Tree of Life" logo are owned by Cigna Intellectual Property, Inc., licensed for use by Cigna Corporation and its operating subsidiaries. All products and services are provided by or through such operating subsidiaries and not by Cigna Corporation. Such operating subsidiaries include Connecticut General Life Insurance Company, Cigna Health and Life Insurance Company, Cigna Behavioral Health, Inc., Cigna Health Management, Inc., and HMO or service company subsidiaries of Cigna Health Corporation. Page 5 of 5