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Hyftor (sirolimus) Prior Authorization with Quantity Limit Program Summary

Policy Number: PH-1188

This program applies to Blue Partner, Commercial, GenPlus, NetResults A series, SourceRx and Health Insurance Marketplace formularies.

POLICY REVIEW CYCLE                                                                                                                                                                           

Effective Date

Date of Origin 

01-01-2025            

04-01-2023

FDA LABELED INDICATIONS AND DOSAGE

Agent(s)

FDA Indication(s)

Notes

Ref#

HYFTOR®

(sirolimus)

Topical gel

Treatment of facial angiofibroma associated with tuberous sclerosis in adults and pediatric patients 6 years of age and older

1

See package insert for FDA prescribing information:  https://dailymed.nlm.nih.gov/dailymed/index.cfm

CLINICAL RATIONALE

Tuberous Sclerosis Complex

Tuberous sclerosis complex (TSC) is an autosomal dominant genetic disorder caused by a mutation in either the TSC1 gene or the TSC2 gene. TSC is characterized by the development of a variety of benign tumors in multiple organs, including the brain, heart, skin, eyes, kidney, lung, and liver. Seizures are the most frequent presenting neurologic feature of TSC, with more than 80% of patients developing seizures during childhood. Facial angiofibromas, the most obvious cutaneous manifestation of TSC, appear as innumerable pink papules that progressively enlarge and multiply over time. The lesions, which are highly visible markers of disease, may spontaneously bleed, impair vision, and cause emotional distress.(2,6) 

Diagnosis of TSC is made by clinical diagnostic criteria or genetic analysis.(2,6) Identification of a pathogenic variant in TSC1 or TSC2 is sufficient for the diagnosis or prediction of TSC regardless of clinical findings, however 10-15% of patients with TSC meeting clinical diagnostic criteria have no mutation identified by conventional genetic testing. Therefore, failure to identify a pathogenic variant in TSC1 or TSC2 does not exclude a diagnosis of TSC. Clinical diagnostic criteria indicate a definitive TSC diagnosis if 2 major features or 1 major feature with 2 minor features are met. Major features are: hypomelanotic macules (greater than or equal to 3, at least 5 mm diameter), angiofibroma (greater than or equal to 3) or fibrous cephalic plaque, ungual fibromas (greater than or equal to 2), shagreen patch, multiple retinal hamartomas, multiple cortical tubers and/or radial migration lines, subependymal nodule (greater than or equal to 2), subependymal giant cell astrocytoma, cardiac rhabdomyoma, lymphangiomyomatosis, angiomyolipomas (greater than or equal to 2); note that a combination of LAM and angiomyolipomas, without other features, does not meet the criteria for a definite diagnosis. Minor features are: "confetti" skin lesions, dental enamel pits (greater than or equal to 3), intraoral fibromas (greater than or equal to 2), retinal achromic patch, multiple renal cysts, nonrenal hamartomas, sclerotic bone lesions.(6)

There is no significant risk of malignant transformation of skin lesions associated with TSC. When not prominent, the skin lesions do not require treatment. However, closer surveillance and intervention is recommended for skin lesions that rapidly change in size or number, and for those that cause pain, bleeding, functional impairment, or social problems. Procedures to improve the appearance of skin lesions include dermabrasion, laser therapy, or surgical removal (excision) of a lesion.(2,6) These procedures are not effective, however, in preventing early lesions and therefore have less than satisfactory outcomes. Sirolimus topical gel is FDA approved for the treatment of facial angiofibroma associated with TSC in patients age 6 years and older. Although there is rapid response in practically all patients, the possibility of recurrence is quite high. For severely disfiguring facial angiofibromas, a combination of laser therapy or dermabrasion in conjunction with topical sirolimus can be very useful.(2) 

Efficacy

Tuberous sclerosis complex (TSC) is associated with genetic defects in the TSC1 and TSC2 genes which results in overactivation of the mTOR pathway and benign tumor formation in multiple organs. Sirolimus inhibits mTOR activation.(1,4,5)

A single, randomized, double-blind, vehicle-controlled, multicenter, Phase 3 trial evaluated Hyftor for the treatment of adults and pediatric patients 6 years of age and older with facial angiofibroma associated with definite TSC. The response rates of angiofibromas at weeks 4, 8, and 12 of treatment were 0 each in the placebo group in contrast to 20% (95% CI, 8%-39%; p = .01), 43% (95% CI, 26%-63%; p < .001), and 60% (95% CI, 41%-77%; p < .001), respectively, in the sirolimus group.(1,5)

In another evaluation of 33 patients with facial angiofibromas associated with TSC, sirolimus gel treatment improved FA associated with TSC in 23 of the 33 (70%) patients after 3 months of treatment. None of the patients discontinued the treatment due to adverse events.(4)

Safety

HYFTOR is contraindicated in patients with a history of hypersensitivity to sirolimus or any other component of HYFTOR.(1)

REFERENCES                                                                                                                                                                           

Number

Reference

1

HYFTOR prescribing information. Nobelpharma America, LLC. March 2022.

2

DiMario FJ, et al. Tuberous Sclerosis. National Organization for Rare Disorders (NORD). Last updated May 2023. Available at https://rarediseases.org/rare-diseases/tuberous-sclerosis/.

3

Reference no longer used.

4

Hatano T, Ohno Y, Imai Y, et al. Improved Health-Related Quality of Life in Patients Treated with Topical Sirolimus for Facial Angiofibroma Associated with Tuberous Sclerosis Complex. Orphanet J Rare Dis. 2020 Jun;15:133.

5

Wataya-Kaneda M, Ohno Y, Fujita Y, et al. Sirolimus Gel Treatment vs Placebo for Facial Angiofibromas in Patients with Tuberous Sclerosis Complex. JAMA Dermatology. 2018 Jul;154(7):781-788.

6

Northrup H, Aronow ME, Bebin EM, et al. Updated International Tuberous Sclerosis Complex Diagnostic Criteria and Surveillance and Management Recommendations. Pediatr Neurol. 2021 Oct;123:50-66.

POLICY AGENT SUMMARY PRIOR AUTHORIZATION

Target Brand Agent(s)

Target Generic Agent(s)

Strength

Targeted MSC

Available MSC

Final Age Limit

Preferred Status

Hyftor

sirolimus gel

0.2 %

M ; N ; O ; Y

N

POLICY AGENT SUMMARY QUANTITY LIMIT

Target Brand Agent Name(s)

Target Generic Agent Name(s)

Strength

QL Amount

Dose Form

Day Supply

Duration

Addtl QL Info

Allowed Exceptions

Targeted NDCs When Exclusions Exist

Hyftor

Sirolimus Gel

0.2 %

7

Tubes

84

DAYS

CLIENT SUMMARY – PRIOR AUTHORIZATION

Target Brand Agent Name(s)

Target Generic Agent Name(s)

Strength

Client Formulary

Hyftor

sirolimus gel

0.2 %

Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; NetResults A Series ; SourceRx

CLIENT SUMMARY – QUANTITY LIMITS

Target Brand Agent Name(s)

Target Generic Agent Name(s)

Strength

Client Formulary

Hyftor

Sirolimus Gel

0.2 %

Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; NetResults A Series ; SourceRx

PRIOR AUTHORIZATION CLINICAL CRITERIA FOR APPROVAL

Module

Clinical Criteria for Approval

Initial Evaluation

Target Agent(s) will be approved when ALL of the following are met:

  1. The patient has a diagnosis of tuberous sclerosis complex (TSC) confirmed by ONE of the following:
    1. The patient has two major features OR one major and two minor features of TSC clinical diagnostic criteria (Major features: hypomelanotic macules [greater than or equal to 3, at least 5 mm diameter], angiofibroma [greater than or equal to 3] or fibrous cephalic plaque, ungual fibromas [greater than or equal to 2], shagreen patch, multiple retinal hamartomas, multiple cortical tubers and/or radial migration lines, subependymal nodule [greater than or equal to 2], subependymal giant cell astrocytoma, cardiac rhabdomyoma, lymphangiomyomatosis (LAM)*, angiomyolipomas* [greater than or equal to 2]; *note that a combination of LAM and angiomyolipomas, without other features, does not meet the criteria for a definite diagnosis. Minor features: "confetti" skin lesions, dental enamel pits [greater than or equal to 3], intraoral fibromas [greater than or equal to 2], retinal achromic patch, multiple renal cysts, nonrenal hamartomas, sclerotic bone lesions) OR
    2. The patient has a pathogenic variant in the TSC1 gene or TSC2 gene confirmed by genetic testing AND
  2. The patient has three or more facial angiofibromas AND
  3. If the patient has an FDA labeled indication, then ONE of the following:
    1. The patient’s age is within FDA labeling for the requested indication for the requested agent OR
    2. There is support for using the requested agent for the patient’s age for the requested indication AND
  4. The prescriber is a specialist in the area of the patient’s diagnosis (e.g., dermatologist, geneticist) or the prescriber has consulted with a specialist in the area of the patient’s diagnosis AND
  5. The patient does NOT have any FDA labeled contraindications to the requested agent

Length of Approval:  12 weeks

NOTE: If Quantity Limit applies, please refer to Quantity Limit Criteria.

 

Renewal Evaluation

Target Agent(s) will be approved when ALL of the following are met:

  1. The patient has been previously approved for the requested agent through the plan’s Prior Authorization process [Note: patients not previously approved for the requested agent will require initial evaluation review] AND
  2. The patient has had clinical benefit with the requested agent AND
  3. The prescriber is a specialist in the area of the patient’s diagnosis (e.g., dermatologist, geneticist) or the prescriber has consulted with a specialist in the area of the patient’s diagnosis AND
  4. The patient does NOT have any FDA labeled contraindications to the requested agent

Length of Approval:  12 months

NOTE: If Quantity Limit applies, please refer to Quantity Limit Criteria.

QUANTITY LIMIT CLINICAL CRITERIA FOR APPROVAL

Module

Clinical Criteria for Approval

Quantity limit for the Target Agent(s) will be approved when ONE of the following is met:

  1. The requested quantity (dose) does NOT exceed the program quantity limit OR
  2. The requested quantity (dose) exceeds the program quantity limit AND ONE of the following:
    1. BOTH of the following:
      1. The requested agent does NOT have a maximum FDA labeled dose for the requested indication AND
      2. There is support for therapy with a higher dose for the requested indication OR
    2. BOTH of the following:
      1. The requested quantity (dose) does NOT exceed the maximum FDA labeled dose for the requested indication AND
      2. There is support for why the requested quantity (dose) cannot be achieved with a lower quantity of a higher strength that does NOT exceed the program quantity limit OR
    3. BOTH of the following:
      1. The requested quantity (dose) exceeds the maximum FDA labeled dose for the requested indication AND
      2. There is support for therapy with a higher dose for the requested indication

Length of Approval: up to 12 months

 

This pharmacy policy is not an authorization, certification, explanation of benefits or a contract. Eligibility and benefits are determined on a case-by-case basis according to the terms of the member’s plan in effect as of the date services are rendered. All pharmacy policies are based on (i) information in FDA approved package inserts (and black box warning, alerts, or other information disseminated by the FDA as applicable); (ii) research of current medical and pharmacy literature; and/or (iii) review of common medical practices in the treatment and diagnosis of disease as of the date hereof. Physicians and other providers are solely responsible for all aspects of medical care and treatment, including the type, quality, and levels of care and treatment.

 The purpose of Blue Cross and Blue Shield of Alabama’s pharmacy policies are to provide a guide to coverage. Pharmacy policies are not intended to dictate to physicians how to practice medicine. Physicians should exercise their medical judgment in providing the care they feel is most appropriate for their patients.

 Neither this policy, nor the successful adjudication of a pharmacy claim, is guarantee of payment.

 

 

 

Commercial _ PS _ Hyftor_sirolimus__PAQL _ProgSum_ 01-01-2025