Facial Angiofibroma: One of the Most Common and Visible Signs of TSC

Tuberous Sclerosis Complex

Tuberous sclerosis complex (TSC) is a genetic multisystemic disease that affects approximately 1 in 6,000 live births.1 It causes noncancerous tumors, or hamartomas, to form throughout the body. These benign tumors can develop in many organs, including the brain, eyes, kidneys, liver, lungs, heart, and skin.1

TSC is an autosomal dominant disorder. It is caused by abnormalities in the TSC1 and TSC2 genes. However, symptoms and severity may differ substantially—even among members of the same family. The distribution, number, size, and location of tumors can vary.1 TSC can be so mild that individuals go undiagnosed, or it can cause significant complications and may even be life-threatening.2
How TSC affects body

Symptoms and complications1

  • Approximately 50% of TSC patients had retinal hamartomas
  • 70%-90% had renal abnormalities
  • Approximately 90% had symptoms of cerebral pathology
  • More than 90% had skin tumors

The skin is one of the most affected organs in people with TSC.3

Facial Angiofibroma

Facial angiofibromas are pink-to-red tumors typically located on the cheeks, nose, and chin, often appearing in a butterfly pattern over the malar eminences and nasolabial folds.1,4

Facial angiofibromas are made up of blood vessels and fibrous tissue and can coalesce to form patches. They can bleed, obstruct the nasal openings, and cause disfigurement.3,5


Facial angiofibroma occurs in approximately 75%-80% of TSC patients, making it the one of the most predominant skin manifestations of this disease.3-5

Impact of facial angiofibroma on patients

Facial angiofibromas can appear in early childhood, becoming more numerous and larger as patients grow older.2 Facial angiofibromas initially cause a ruddy appearance on the cheeks. However, they eventually become rougher and cobblestoned.1
Left untreated, facial angiofibromas can cause disfigurement.5 These tumors may also impose a psychosocial burden on patients.3 Patients have reported that facial angiofibroma may have adverse effects on appearance and self-image, prompting some to avoid social situations.6

Unmet need in the treatment landscape

These tumors are sometimes treated with invasive modalities. However, these procedures may require anesthesia. Invasive treatments can also be difficult to administer in patients with extensive angiofibroma or severe intellectual impairments.4

Interventional treatments for facial angiofibroma include7:

  • Radiofrequency ablation
  • Cryotherapy
  • Electrocoagulation
  • Dermabrasion
  • Laser treatments

These treatments can be invasive and may require anesthesia.7

Indication

HYFTOR® is an mTOR inhibitor immunosuppressant indicated for the treatment of facial angiofibroma associated with tuberous sclerosis in adults and pediatric patients 6 years of age and older.

Important Safety Information

CONTRAINDICATIONS
HYFTOR® is contraindicated in patients with a history of hypersensitivity to sirolimus or any other component of HYFTOR®.
WARNINGS AND PRECAUTIONS

  • Hypersensitivity Reactions: Hypersensitivity reactions, including anaphylactic/anaphylactoid reactions, angioedema, exfoliative dermatitis, and hypersensitivity vasculitis, have been associated with the oral administration of sirolimus. The concomitant use of HYFTOR® with other drugs known to cause angioedema, such as angiotensin-converting enzyme (ACE) inhibitors, may increase the risk of developing angioedema. Elevated sirolimus levels may also potentiate angioedema. Discontinue HYFTOR® immediately if symptoms occur.
  • Serious Infection: Serious infections, including opportunistic infections, have been reported after oral administration of sirolimus. Cases of progressive multifocal leukoencephalopathy (PML), sometimes fatal, have been reported in patients treated with oral sirolimus. Discontinue HYFTOR® immediately if symptoms of infection occur.
  • Malignancy: Lymphoma and other malignancies, particularly of the skin, have been observed after oral administration of sirolimus. Patients should minimize or avoid exposure to natural or artificial sunlight (tanning beds or UVA/B treatment) while using HYFTOR®. If patients need to be outdoors, they should wear protective clothing and discuss other sun protection measures with their physician.
  • Hyperlipidemia: Increased serum cholesterol and triglycerides requiring treatment have been observed with oral administration of sirolimus. Monitor for hyperlipidemia during treatment.
  • Interstitial Lung Disease/Non-Infectious Pneumonitis: Cases of interstitial lung disease (ILD) (including pneumonitis, bronchiolitis obliterans organizing pneumonia [BOOP], and pulmonary fibrosis), some fatal, with no identified infectious etiology have occurred in patients receiving oral sirolimus. Discontinue HYFTOR® immediately if symptoms of ILD occur.
  • Immunizations: During treatment with HYFTOR®, vaccinations may be less effective. Complete all age-appropriate vaccinations as recommended by current immunization guidelines prior to initiating treatment with HYFTOR®. The use of live vaccines should be avoided during treatment with HYFTOR®.
  • Embryo-Fetal Toxicity: Based on animal studies and the mechanism of action, oral sirolimus can cause fetal harm when administered to a pregnant woman. In animal studies, oral sirolimus caused embryo-fetal toxicity when administered during the period of organogenesis at maternal exposures that were equal to or less than human exposures at the recommended lowest starting dose. HYFTOR® is systemically absorbed after topical administration and may result in fetal exposure. Advise pregnant women of the potential risk to a fetus. Advise female patients of reproductive potential to avoid becoming pregnant. They should use effective contraception prior to, throughout treatment and for 12 weeks after the final dose of HYFTOR®.
  • Male Infertility: Azoospermia or oligospermia has been observed after oral administration of sirolimus. Advise males that HYFTOR® may impair fertility.


ADVERSE REACTIONS

The most common adverse reactions (≥1%) are dry skin, application site irritation, pruritus, acne, acneiform dermatitis, ocular hyperemia, skin hemorrhage, and skin irritation.

USE IN SPECIFIC POPULATIONS

  • Pregnancy: Based on animal studies and mechanism of action, oral sirolimus can cause fetal harm when administered to a pregnant woman. HYFTOR® is systemically absorbed after topical administration and may result in fetal exposure.
  • Lactation: Breastfeeding is not recommended during treatment with HYFTOR®.
  • Infertility: Based on clinical findings and animal studies, male and female fertility may be compromised by the treatment with sirolimus.

Please see full Prescribing Information for additional safety information.

You are encouraged to report side effects of prescription drugs to the FDA. Visit www.fda.gov/medwatch, or call 1-800-FDA-1088. You may also reach out to Nobelpharma America, LLC at 1-877-375-0825

Indication

HYFTOR® is an mTOR inhibitor immunosuppressant indicated for the treatment of facial angiofibroma associated with tuberous sclerosis in adults and pediatric patients 6 years of age and older.

Important Safety Information

CONTRAINDICATIONS
HYFTOR® is contraindicated in patients with a history of hypersensitivity to sirolimus or any other component of HYFTOR®.

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  1. Curatolo P, Bombardieri R, Jozwiak S. Tuberous sclerosis. Lancet. 2008;372(9639):657-668. doi:10.1016/
    S0140-6736(08)61279-9
  2. National Organization for Rare Disorders (NORD). Tuberous sclerosis. Accessed August 25, 2020. http://
    rarediseases.org/rare-diseases/tuberous-sclerosis
  3. Cinar SL, Kartal D, Bayram AK, et al. Topical sirolimus for the treatment of angiofibromas in tuberous sclerosis. Indian J Dermatol Venereol Leprol. 2017;83(1):27-32. doi:10.4103/0378-6323.190844
  4. Wataya-Kaneda M, Ohno Y, Fujita Y, et al. Sirolimus gel treatment vs placebo for facial angiofibromas in patients with tuberous sclerosis complex: a randomized clinical trial. JAMA Dermatol. 2018;154(7):781-788. doi:10.1001/ jamadermatol.2018.1408
  5. Northrup H, Koenig MK, Pearson DA, Au KS. Tuberous sclerosis complex. July 13, 1999. Updated April 16, 2020. Accessed April 21, 2021. In: Adam MP, Ardinger HH, Pagon RA, et al, eds. GeneReviews. University of Washington, Seattle; 1993-2021.
  6. Tuberous Sclerosis Alliance. Skin. Updated December 2013. Accessed June 8, 2020. https://www.tsalliance.org/about-tsc/signs-and-symptoms-of-tsc/skin
  7. Salido-Vallejo R, Garnacho-Saucedo G, Moreno-Giménez JC. Current options for the treatment of facial
    angiofibromas. Actas Dermosifiliogr. 2014;105(6):558-568. doi:10.1016/j.ad.2012.11.020
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