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About TIO

TIO is an acquired form of hypophosphatemia1

Tumor-induced osteomalacia, or TIO, is an extremely rare, difficult to diagnose disease—to date, there have only been about 1000 cases reported. The mean age of diagnosis is 45 years with a wide age range, including cases reported in children.2-4

TIO is an acquired form of hypophosphatemia caused by slow growing, benign, phosphaturic mesenchymal tumors that can be located anywhere in the body in soft tissues or bones. These tumors secrete excess fibroblast growth factor 23 (FGF23), which results in hypophosphatemia and osteomalacia.3,4

The underlying cause of hypophosphatemia in TIO

In normal homeostasis3,4:

CRYSVITA monoclonal antibody binding to FGF23

Normal FGF23 activity

Kidneys reabsorbing phosphorus

FGF23 plays an important role in phosphorus homeostasis via renal excretion

Small intestine reabsorbing phosphorus

Intestinal phosphorus absorption also regulates phosphorus homeostasis

Bone with more mineralization representing healing of rickets and osteomalacia

Normal bone mineralization

CRYSVITA monoclonal antibody binding to FGF23

Normal FGF23 activity

Kidneys reabsorbing phosphorus

FGF23 plays an important role in phosphorus homeostasis via renal excretion

Small intestine reabsorbing phosphorus

Intestinal phosphorus absorption also regulates phosphorus homeostasis

Bone with more mineralization representing healing of rickets and osteomalacia

Normal bone mineralization

In TIO3-5:

Tumor expressing increased production of FGF23

Tumors express increased production of FGF23

Kidney showing reduced phosphorus reabsorption

Excess FGF23 results in reduced renal phosphorus reabsorption or "phosphate wasting"

Small intestine with decreased phosphorus absorption

Reduced renal production of active vitamin D results in decreased intestinal phosphorus absorption

Bone with weakened matrix representing hypophosphatemia

Resulting in chronic hypophosphatemia leading to osteomalacia

Tumor expressing increased production of FGF23

Tumors express increased production of FGF23

Kidney showing reduced phosphorus reabsorption

Excess FGF23 results in reduced renal phosphorus reabsorption or "phosphate wasting"

Small intestine with decreased phosphorus absorption

Reduced renal production of active vitamin D results in decreased intestinal phosphorus absorption

Bone with weakened matrix representing hypophosphatemia

Resulting in chronic hypophosphatemia leading to osteomalacia

Tumor removal can be curative, but may not be possible under certain circumstances.2

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Indication

CRYSVITA® (burosumab-twza) is a fibroblast growth factor 23 (FGF23) blocking antibody indicated for the treatment of FGF23-related hypophosphatemia in tumor-induced osteomalacia (TIO) associated with phosphaturic mesenchymal tumors that cannot be curatively resected or localized in adult and pediatric patients 2 years of age and older.

Indication

CRYSVITA® (burosumab-twza) is a fibroblast growth factor 23 (FGF23) blocking antibody indicated for the treatment of FGF23-related hypophosphatemia in tumor-induced osteomalacia (TIO) associated with phosphaturic mesenchymal tumors that cannot be curatively resected or localized in adult and pediatric patients 2 years of age and older.

Important Safety Information

CONTRAINDICATIONS

CRYSVITA is contraindicated:

  • In concomitant use with oral phosphate and/or active vitamin D analogs (e.g., calcitriol, paricalcitol, doxercalciferol, calcifediol) due to the risk of hyperphosphatemia.
  • When serum phosphorus is within or above the normal range for age.
  • In patients with severe renal impairment or end stage renal disease because these conditions are associated with abnormal mineral metabolism.

WARNINGS AND PRECAUTIONS

Hypersensitivity

  • Hypersensitivity reactions (e.g., rash, urticaria) have been reported in patients with CRYSVITA. Discontinue CRYSVITA if serious hypersensitivity reactions occur and initiate appropriate medical treatment.

Hyperphosphatemia and Risk of Nephrocalcinosis

  • Increases in serum phosphorus to above the upper limit of normal may be associated with an increased risk of nephrocalcinosis. For patients already taking CRYSVITA, dose interruption and/or dose reduction may be required based on a patient’s serum phosphorus levels.
  • Patients who undergo treatment of the underlying tumor should have dosing interrupted and adjusted to prevent hyperphosphatemia.

Injection Site Reactions

  • Administration of CRYSVITA may result in local injection site reactions. Discontinue CRYSVITA if severe injection site reactions occur and administer appropriate medical treatment.

ADVERSE REACTIONS

Adult Patients

  • Adverse reactions reported in more than 10% of CRYSVITA-treated adult TIO patients in two studies are: tooth abscess (19%), muscle spasms (19%), dizziness (15%), constipation (15%), injection site reaction (15%), rash (15%), and headache (11%).

USE IN SPECIFIC POPULATIONS

  • There are no available data on CRYSVITA use in pregnant women to inform a drug-associated risk of adverse developmental outcomes. Serum phosphorus levels should be monitored throughout pregnancy. Report pregnancies to the Kyowa Kirin, Inc. Adverse Event reporting line 1-844-768-3544.
  • There is no information regarding the presence of CRYSVITA in human milk or the effects of CRYSVITA on milk production or the breastfed infant. Therefore, the developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for CRYSVITA and any potential adverse effects on the breastfed infant from CRYSVITA or from the underlying maternal condition.

PATIENT COUNSELING INFORMATION

  • Advise patients not to use any oral phosphate and/or active vitamin D analog products.
  • Instruct patients to contact their physician if hypersensitivity reactions, injection site reactions, and restless legs syndrome induction or worsening of symptoms occur.

You may report side effects to the FDA at (800) FDA-1088 or www.fda.gov/medwatch. You may also report side effects to Kyowa Kirin, Inc. at 1-844-768-3544.

For important risk and use information, please see the full Prescribing Information for CRYSVITA.

Indication

CRYSVITA® (burosumab-twza) is a fibroblast growth factor 23 (FGF23) blocking antibody indicated for the treatment of FGF23-related hypophosphatemia in tumor-induced osteomalacia (TIO) associated with phosphaturic mesenchymal tumors that cannot be curatively resected or localized in adult and pediatric patients 2 years of age and older.

Important Safety Information

CONTRAINDICATIONS

CRYSVITA is contraindicated:

  • In concomitant use with oral phosphate and/or active vitamin D analogs (e.g., calcitriol, paricalcitol, doxercalciferol, calcifediol) due to the risk of hyperphosphatemia.
  • When serum phosphorus is within or above the normal range for age.
  • In patients with severe renal impairment or end stage renal disease because these conditions are associated with abnormal mineral metabolism.

WARNINGS AND PRECAUTIONS

Hypersensitivity

  • Hypersensitivity reactions (e.g., rash, urticaria) have been reported in patients with CRYSVITA. Discontinue CRYSVITA if serious hypersensitivity reactions occur and initiate appropriate medical treatment.

Hyperphosphatemia and Risk of Nephrocalcinosis

  • Increases in serum phosphorus to above the upper limit of normal may be associated with an increased risk of nephrocalcinosis. For patients already taking CRYSVITA, dose interruption and/or dose reduction may be required based on a patient’s serum phosphorus levels.
  • Patients who undergo treatment of the underlying tumor should have dosing interrupted and adjusted to prevent hyperphosphatemia.

Injection Site Reactions

  • Administration of CRYSVITA may result in local injection site reactions. Discontinue CRYSVITA if severe injection site reactions occur and administer appropriate medical treatment.

ADVERSE REACTIONS

Adult Patients

  • Adverse reactions reported in more than 10% of CRYSVITA-treated adult TIO patients in two studies are: tooth abscess (19%), muscle spasms (19%), dizziness (15%), constipation (15%), injection site reaction (15%), rash (15%), and headache (11%).

USE IN SPECIFIC POPULATIONS

  • There are no available data on CRYSVITA use in pregnant women to inform a drug-associated risk of adverse developmental outcomes. Serum phosphorus levels should be monitored throughout pregnancy. Report pregnancies to the Kyowa Kirin, Inc. Adverse Event reporting line 1-844-768-3544.
  • There is no information regarding the presence of CRYSVITA in human milk or the effects of CRYSVITA on milk production or the breastfed infant. Therefore, the developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for CRYSVITA and any potential adverse effects on the breastfed infant from CRYSVITA or from the underlying maternal condition.

PATIENT COUNSELING INFORMATION

  • Advise patients not to use any oral phosphate and/or active vitamin D analog products.
  • Instruct patients to contact their physician if hypersensitivity reactions, injection site reactions, and restless legs syndrome induction or worsening of symptoms occur.

You may report side effects to the FDA at (800) FDA-1088 or www.fda.gov/medwatch. You may also report side effects to Kyowa Kirin, Inc. at 1-844-768-3544.

For important risk and use information, please see the full Prescribing Information for CRYSVITA.

References:

1. Farrow EG, White KE. Tumor-induced osteomalacia. Expert Rev Endocrinol Metab. 2009;4(5):435-442. doi:10.1586/eem.09.27 2. Brandi ML, Clunie GPR, Houillier P, et al. Challenges in the management of tumor-induced osteomalacia (TIO). Bone. 2021;152:116064. doi:10.1016/j.bone.2021.116064 3. Dahir K, Zanchetta MB, Stanciu I, et al. Diagnosis and management of tumor-induced osteomalacia: perspectives from clinical experience. J Endocr Soc. 2021;5(9):bvab099. doi:10.1210/jendso/bvab099 4. Minisola S, Peacock M, Fukumoto S, et al. Tumour-induced osteomalacia. Nat Rev Dis Primers. 2017;3:17044. doi:10.1038/nrdp.2017.44 5. Aono Y, Yamazaki Y, Yasutake J, et al. Therapeutic effects of anti-FGF23 antibodies in hypophosphatemic rickets/osteomalacia. J Bone Miner Res. 2009;24(11):1879-1888. doi:10.1359/jbmr.090509