Medical Drug Criteria (MDC)
Policy Num: M5.001.013
Policy Name: Ruconest (C1 Esterase Inhibitor [recombinant])
Policy ID: [M5.001.013] [Ac / Mg / M + / P+] [0.00.00]
Last Review: May 10, 2024
Next Review: May 20, 2025
Related MDC: None
| Population Reference No. | Populations |
| 1 | Individuals: · Treatment of acute abdominal, peripheral, or facial attacks of Hereditary Angioedema (HAE) |
C-1 esterase inhibitor protein is one of nine complement proteins found in the blood that works with the body's immune system in coagulation, fighting disease and the development of inflammation. Hereditary angioedema (HAE) is a rare, but life-threatening genetic disorder of the immune system characterized by edema in various parts of the body, including the extremities, intestines, face, and airway.
Coverage is provided in the following conditions:
• Patient is at least 13 years of age; AND
Universal Criteria
• Must be prescribed by, or in consultation with, a specialist in: allergy, immunology, hematology, pulmonology, or medical genetics; AND
• Patient does not have a history of allergy to rabbits or rabbit-derived products; AND
• Confirmation the patient is avoiding the following possible triggers for HAE attacks:
o Estrogen-containing oral contraceptive agents AND hormone replacement therapy; AND
o Antihypertensive agents containing ACE inhibitors; AND
o Dipeptidyl peptidase IV (DPP-IV) inhibitors (e.g., sitagliptin); AND
o Neprilysin inhibitors (e.g., sacubitril); AND
Patient has a history of moderate to severe cutaneous attacks (without concomitant hives)OR abdominal attacks OR mild to severe airway swelling attacks of HAE (i.e. debilitating cutaneous/gastrointestinal symptoms OR laryngeal/pharyngeal/tongue swelling); AND
Patient has one of the following clinical presentations consistent with a HAE subtype§,which must be confirmed by repeat blood testing (treatment for acute attack should not bedelayed for confirmatory testing):
| HAE I (C1-Inhibitor deficiency) |
| Low C1 inhibitor (C1-INH) antigenic level (C1-INH antigenic level below the lower limit of normal as defined by the laboratory performing the test); AND Low C4 level (C4 below the lower limit of normal as defined by the laboratory performing the test); AND Low C1-INH functional level (C1-INH functional level below the lower limit of normal as defined by the laboratory performing the test); AND Patient has a family history of HAE; OR Acquired angioedema has been ruled out (i.e., patient onset of symptoms occur prior to 30 years old, normal C1q levels, patient does not have underlying disease such as lymphoma or benign monoclonal gammopathy [MGUS], etc.)
|
| HAE II (C1-Inhibitor dysfunction) |
| Normal to elevated C1-INH antigenic level; AND Low C4 level (C4 below the lower limit of normal as defined by the laboratory performing the test); AND Low C1-INH functional level (C1-INH functional level below the lower limit of normal as defined by the laboratory performing the test) |
| HAE with normal C1INH (formerly known as HAE III) |
| Normal C1-INH antigenic level; AND Normal C4 level; AND Normal C1-INH functional level; AND Repeat blood testing during an attack has confirmed the patient does not have abnormal lab values indicative of HAE I or HAE II; AND Either of the following: o Patient has a known HAE-causing mutation (e.g., mutation of coagulation factor XII gene [F12 mutation], mutation in the angiopoietin-1 gene, mutation in the plasminogen gene, mutation in the kininogen 1 gene, mutation in the myoferlin gene, mutation in the heparan sulfate 3-O-sulfotransferase 6 gene, etc.); OR o Patient has a family history of HAE and documented evidence of lack of efficacy of chronic high-dose antihistamine therapy (e.g. cetirizine standard dosing at up to four times daily |
Patient continues to meet the universal and other indication-specific relevant criteria identified in section III; ANDAbsence of unacceptable toxicity from the drug. Examples of unacceptable toxicity include: severe hypersensitivity reactions (including anaphylaxis), serious thromboembolic events (arterial or venous), etc.; AND
The cumulative amount of medication(s) the patient has on-hand, indicated for the acute treatment of HAE, will be taken into account when authorizing. The authorization will provide a sufficient quantity in order for the patient to have a cumulative amount of HAEmedication(s) on-hand in order to treat up to 4 acute attacks per 4 weeks for the duration of the authorization (unless otherwise specified).Coverage will be provided for 12 weeks and is eligible for renewal (unless otherwise specified). The cumulative amount of medication(s) the patient has on-hand, indicated for the acute treatment of HAE, will be taken into account when authorizing.
The authorization will provide a sufficient quantity in order for the patient to have a cumulative amount of HAE medication(s) on-hand in order to treat up to 4 acute attacks per 4 weeks for the duration of the authorization (unless otherwise specified).
Body weight < 84 kg:
Administer 50 international units (IU) per kg body weight by intravenous injection Body weight ≥ 84 kg:
Administer 4200 IU (2 vials) by intravenous injection If the attack symptoms persist, an additional (second) dose can be administered at the recommended dose level. Do not exceed 4200 IU per dose. No more than two doses should be administered within a 24 hour period.
**Note: Patients may self-administer Ruconest after being instructed by their healthcare provider.
A. Quantity Limit (max daily dose) [NDC Unit]:
• Ruconest 2100 IU single-use vial: 16 vials every 28 days
• 3360 billable units per 28 days
Submission of medical records (chart notes) related to the medical necessity criteria is REQUIRED on all requests for authorizations. Records will be reviewed at the time of submission. Please provide documentation related to diagnosis, step therapy, and clinical markers (i.e. genetic and mutational testing) supporting initiation when applicable. Medical records may be submitted via direct upload through the PA web portal or by fax.
NONE
As stated in the policy.
Medicare coverage for outpatient (Part B) drugs is outlined in the Medicare Benefit Policy Manual (Pub. 100-2), Chapter 15, §50 Drugs and Biologicals. In addition, National Coverage Determination (NCD), Local Coverage Determinations (LCDs), and Local Coverage Articles (LCAs) may exist and compliance with these policies is required where applicable. They can be found at: https://www.cms.gov/medicare-coverage-database/search.aspx. Additional indications may be covered at the discretion of the health plan.
1. Ruconest [package insert]. Warren, NJ; Pharming Healthcare, Inc; April 2020. Accessed September 2023.
2. Riedl MA, Grivcheva-Panovska V, Moldovan D, et al. Recombinant human C1 esterase inhibitor for prophylaxis of hereditary angio-oedema: a phase 2, multicentre, randomised, double-blind, placebo-controlled crossover trial. Lancet. 2017;390(10102):1595-1602.
3. Bowen T, Cicardi M, Farkas H, et al. Canadian 2003 International Consensus Algorithm For the Diagnosis, Therapy, and Management of Hereditary Angioedema. J Allergy Clin Immunol. 2004 Sep;114(3):629-37.
4. Bygum A, Andersen KE, Mikkelsen CS. Self-administration of intravenous C1-inhibitor therapy for hereditary angioedema and associated quality of life benefits. Eur J Dermatol. Mar-Apr 2009;19(2):147-151.
5. Bowen T, Cicardi M, Farkas H, et al. 2010 International consensus algorithm for the diagnosis, therapy and management of hereditary angioedema. Allergy Asthma Clin Immunol. 2010;6(1):24.
6. Craig T, Aygören-Pürsün E, Bork K, et al. WAO Guideline for the Management of Hereditary Angioedema. World Allergy Organ J. 2012 Dec;5(12):182-99.
7. Gompels MM, Lock RJ, Abinun M, et al. C1 inhibitor deficiency: consensus document. Clin Exp Immunol. 2005;139(3):379.
8. Betschel S, Badiou J, Binkley K, et al. Canadian hereditary angioedema guideline. Asthma Clin Immunol. 2014 Oct 24;10(1):50. doi: 10.1186/1710-1492-10-50.
9. Zuraw BL, Bernstein JA, Lang DM, et al. A focused parameter update: hereditary angioedema, acquired C1 inhibitor deficiency, and angiotensin-converting enzyme inhibitorassociated angioedema. J Allergy Clin Immunol. 2013 Jun;131(6):1491-3. doi:10.1016/j.jaci.2013.03.034.
10. Zuraw BL, Banerji A, Bernstein JA, et al. US Hereditary Angioedema Association Medical Advisory Board 2013 recommendations for the management of hereditary angioedema due to C1 inhibitor deficiency. J Allergy Clin Immunol Pract. 2013 Sep-Oct;1(5):458-67.
11. Frank MM, Zuraw B, Banerji A, et al. Management of children with Hereditary Angioedema due to C1 Inhibitor deficiency. Pediatrics. 2016 Nov. 135(5)
12. Zuraw BL, Bork K, Binkley KE, et al. Hereditary angioedema with normal C1 inhibitor function: Consensus of an international expert panel. Allergy Asthma Proc. 2012;33 Suppl 1:145-156.
13. Maurer M, Mager M, Ansotegui I, et al. The international WAO/EAACI guideline for the management of hereditary angioedema-The 2017 revision and update. Allergy. 2018 Jan 10. doi: 10.1111/all.13384.
14. Lang DM, Aberer W, Bernstein JA, et al. International consensus on hereditary and acquired angioedema. Ann Alergy Asthma Immunol. 2012;109:395-402.
15. Wintenberger C, Boccon-Gibod I, Launay D, et al. Tranexamic acid as maintenance treatment for non-histaminergic angioedema: analysis of efficacy and safety in 37 patients. Clin Exp Immunol. 2014 Oct; 178(1): 112–117.
16. Saule C, Boccon-Gibod I, Fain O, et al. Benefits of progestin contraception in non-allergic angioedema. Clin Exp Allergy. 2013 Apr;43(4):475-82.
17. Frank MM, Sergent JS, Kane MA, et al. Epsilon aminocaproic acid therapy of hereditary angioneurotic edema; a double-blind study. N Engl J Med. 1972:286:808-812.
18. Riedl MA, Bernstein JA, Li H, et al. Recombinant human C1-esterase inhibitor relieves symptoms of hereditary angioedema attacks: phase 3, randomized, placebo-controlled trial. Ann Allergy Asthma Immunol. 2014;112(2):163-169.e1.
19. Betschel S, Badiou J, Binkley K, et al. The International/Canadian Hereditary Angioedema Guideline. Allergy Asthma Clin Immunol. 2019; 15: 72. Published online 2019 Nov 25. doi: 10.1186/s13223-019-0376-8.
20. Busse PJ, Christiansen SC, Riedl MA, et al. US HAEA Medical Advisory Board 2020 Guidelines for the Management of Hereditary Angioedema. J Allergy Clin Immunol Pract. 2021 Jan;9(1):132-150.e3. doi: 10.1016/j.jaip.2020.08.046.
21. Maurer M, Magerl M, Betschel S, et al. The international WAO/EAACI guideline for the management of hereditary angioedema – The 2021 revision and update. Allergy. 2021 Nov 22. doi: 10.1111/all.15214
| Codes | Number | Description |
| HCPCS | J0596 | Injection, c1 esterase inhibitor (recombinant), ruconest, 10 units; 1 billable unit = 10 units |
| ICD-10 | D84.1 | Defects in the complement system |
| Date | Action | Description |
| 5/10/2024 | Table Policy | PR Law No. 62, April 16, 2024, establishes mandatory coverage for HAE. Triple-S is evaluating its drug selection. Once it is defended a policy that address the class will e presented for approval. Policy presented at the Utilization Management Committee. Committee recommeded to table policy until final coverage desicion by Triple S. |
| 02/19/2024 | Review MDC | No change MDC Statement. Reference Added. |
| 02/23/2023 | New MDC | New medical drug criteria for Ruconest ® (C1 Esterase Inhibitor [recombinant]) |