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The standing height z-score1,3

  • The standing height z-score was used as a measurement for growth
  • The “stature-for-age” z-score was determined based on a percentile basis using the Centers for Disease Control and Prevention/National Center for Health Statistics (CDC/NCHS) Clinical Growth Charts
  • Standing height was used to calculate the stature-for-age z-score based on standardized age- and sex-adjusted stature from the CDC

Efficacy in children

Actor portrayal

person

A phase 3 study showed that CRYSVITA1:

  • Helped heal rickets and reduce rickets severity
  • Increased growth
  • Increased and sustained serum phosphorus levels

Study design

CRYSVITA was studied in a 64-week randomized, open-label phase 3 study (Study 1) in 61 children with XLH between 1 and 12 years of age. Study 1 compared treatment with CRYSVITA (n=29) every 2 weeks to conventional therapy (n=32) that included oral phosphate and active vitamin D supplements. Patients randomized to CRYSVITA received a mean dose of approximately 0.90 mg/kg (range 0.8-1.2 mg/kg) every 2 weeks.1

Primary endpoint:

  • Healing of rickets at week 40
    • As assessed by Radiographic Global Impression of Change (RGI-C) scores

Secondary endpoints:

Change from baseline, comparing CRYSVITA with conventional therapy in:

  • Lower extremity skeletal abnormalities
    • As assessed by the RGI-C long leg score
  • Severity of rickets
    • As measured by total Thacher Rickets Severity Score (RSS)
  • Growth
    • As measured by standing height z-score
  • Serum phosphorus levels
  • Alkaline phosphatase (ALP) activity

Safety: Number of subjects with adverse events (AEs), serious adverse events (SAEs), and AEs leading to discontinuation.

CRYSVITA was evaluated in 2 other phase 2 studies. To learn more about Study 2 and Study 3, please see full Prescribing Information.

Disease burden at baseline1

person

No pediatric patients discontinued CRYSVITA treatment in the study.1

RICKETS HEALING

CRYSVITA significantly improved healing of rickets compared with conventional therapy1,2

Mean radiographic global impression of change (RGI-C) in rickets severity*

*RGI-C at week 40 was the primary endpoint of the study. The estimates of LS mean for week 40 are from an ANCOVA model accounting for treatment group, baseline RSS, and baseline age stratification factor. The estimates for week 64 are from a GEE model accounting for treatment group, visit, treatment by visit interaction, baseline RSS, and baseline age stratification factor.1

ANCOVA=analysis of covariance; CI=confidence interval; GEE=generalized estimation equation; LS=least squares; RGI-C=Radiographic Global Impression of Change; RSS=Thacher Rickets Severity Score; SE=standard error.

At week 40, mean RGI-C score in patients treated with CRYSVITA was +1.9, indicating that healing of rickets occurred. Twenty-one out of 29 patients achieved an RGI-C score of ≥+2.0, indicating substantial healing of rickets. At week 64, patients treated with CRYSVITA maintained a mean RGI-C global score of +2.06.1,2

RICKETS HEALING

CRYSVITA helped significantly more patients achieve substantial healing of rickets compared with conventional therapy1,2

Knee and leg bones with an upwards arrow next to it representing the healing of rickets due to CRYSVITA
72%

of patients receiving CRYSVITA achieved substantial healing† of rickets

Versus icon comparing the rickets healing data
6%

of patients receiving conventional therapy

†An RGI-C score of +2.0 indicates a substantial healing of rickets.1,2

At week 40, 72% (21 out of 29) of patients achieved substantial healing (RGI-C score of ≥+2.0) of rickets compared with 6% (2 out of 32) of patients receiving conventional therapy (P<0.0001). These results were maintained at week 64.1,2

RICKETS HEALING

CRYSVITA led to a 64% reduction in rickets severity from baseline to week 40 and maintained at week 641-3

Mean total rickets severity score‡

Bar graphs showing 64% reduction in rickets severity at week 40 with CRYSVITA and 70% reduction in rickets severity at week 64

‡ The estimates of LS mean for week 40 are from an ANCOVA model accounting for treatment group, baseline RSS, and baseline age stratification factor. The estimates for week 64 are from a GEE model accounting for treatment group, visit, treatment-by-visit interaction, baseline RSS, and baseline age stratification factor.1,2

Treatment every 2 weeks with CRYSVITA showed superior reduction in mean total rickets severity, compared with conventional therapy, as assessed using the Thacher Rickets Severity Score (RSS). A reduced RSS score indicates improvement in rickets severity.1,2

CRYSVITA demonstrated greater improvement in lower extremity skeletal abnormalities1,2

At week 64, CRYSVITA maintained greater improvement in lower extremity skeletal abnormalities compared with conventional therapy (LS mean [standard error]: +1.25 [0.17] vs +0.29 [0.12]).1,2§

§ The estimates for week 64 are from a generalized estimating equation (GEE) model accounting for treatment group, visit, treatment-by-visit interaction, and baseline age stratification factor.1-3

Radiographic examples of lower extremity skeletal abnormality improvement with CRYSVITA

The radiographic examples are of a patient with XLH (female, 2.9 years of age) who received CRYSVITA every 2 weeks for 64 weeks, compared with a patient (also female, 2.9 years of age) who continued on conventional therapy.1,4

A set of X-ray images of a child's legs showing lower extremity abnormality improvement from baseline to week 64 with CRYSVITA
A set of X-ray images of a child's legs showing lack of lower extremity abnormality improvement from baseline to week 64 with conventional therapy

Individual results may vary.

GROWTH INCREASE

CRYSVITA significantly increased growth compared to conventional therapy1,2

Height z-scores with CRYSVITA every 2 weeks or with conventional therapy||

height z-scores graph

||The estimates of LS mean, SE, and 95% CI are from a GEE model, which included change from baseline for recumbent length/standing height z-score as the dependent variable, treatment group, visit, interaction between treatment group by visit, and baseline RSS stratification as factors; and age and baseline recumbent length/standing height z-score as continuous covariates, with exchangeable covariance structure.2

CI=confidence interval.

At 64 weeks, CRYSVITA treatment increased standing mean (SD) height z-score from -2.32 (1.17) at baseline to -2.11 (1.11) in patients who received CRYSVITA every 2 weeks compared with a mean (SD) height z-score increase from -2.05 (0.87) at baseline to -2.03 (0.83) in patients who received conventional therapy.1

CHANGE IN SERUM PHOSPHORUS LEVELS

CRYSVITA increased and maintained serum phosphorus levels1,2

Mean serum phosphorus levels in children receiving CRYSVITA or conventional therapy

person

Serum phosphorus level (mg/dL) (mean ±SD). Lower limit of normal (LLN) is 3.2 mg/dL.1

#Normal levels of serum phosphorus range from 3.2 mg/dL to 6.1 mg/dL. Note that the normal levels of serum phosphorus vary by age and sex.3,5,6

SD=standard deviation.

An increase in serum phosphorus levels compared with conventional therapy was observed with CRYSVITA at week 2 and maintained at week 64.1,2

CRYSVITA increased and sustained the tubular maximum for phosphorus reabsorption per glomerular filtration rate (TmP/GFR) compared with conventional therapy from baseline to week 641

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ENROLLMENT FORM

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Set up time with a representative to talk more about CRYSVITA,
or sign up for more information on CRYSVITA for the treatment of XLH.

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Indication

CRYSVITA® (burosumab-twza) is a fibroblast growth factor 23 (FGF23) blocking antibody indicated for the treatment of X-linked hypophosphatemia (XLH) in adult and pediatric patients 6 months of age and older.

Indication

CRYSVITA® (burosumab-twza) is a fibroblast growth factor 23 (FGF23) blocking antibody indicated for the treatment of X-linked hypophosphatemia (XLH) in adult and pediatric patients 6 months 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.

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

Pediatric Patients

  • Adverse reactions reported in 10% or more of CRYSVITA-treated pediatric XLH patients across three studies are: pyrexia (55%, 44%, and 62%), injection site reaction (52%, 67%, and 23%), cough (52%), vomiting (41%, 48%, and 46%), pain in extremity (38%, 46%, and 23%), headache (34% and 73%), tooth abscess (34%, 15%, and 23%), dental caries (31%), diarrhea (24%), vitamin D decreased (24%, 37%, and 15%), toothache (23% and 15%), constipation (17%), myalgia (17%), rash (14% and 27%), dizziness (15%), and nausea (10%).
  • Postmarketing experience reported in CRYSVITA-treated pediatric XLH patients: blood phosphorus increased.

Adult Patients

  • Adverse reactions reported in more than 5% of CRYSVITA-treated adult XLH patients and in at least 2 patients more than placebo in one study are: back pain (15%), headache (13%), tooth infection (13%), restless legs syndrome (12%), vitamin D decreased (12%), dizziness (10%), constipation (9%), muscle spasms (7%), and blood phosphorus increased (6%).
  • Spinal stenosis is prevalent in adults with XLH, and spinal cord compression has been reported. It is unknown if CRYSVITA therapy exacerbates spinal stenosis or spinal cord compression.

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 at 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 X-linked hypophosphatemia (XLH) in adult and pediatric patients 6 months 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.

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

Pediatric Patients

  • Adverse reactions reported in 10% or more of CRYSVITA-treated pediatric XLH patients across three studies are: pyrexia (55%, 44%, and 62%), injection site reaction (52%, 67%, and 23%), cough (52%), vomiting (41%, 48%, and 46%), pain in extremity (38%, 46%, and 23%), headache (34% and 73%), tooth abscess (34%, 15%, and 23%), dental caries (31%), diarrhea (24%), vitamin D decreased (24%, 37%, and 15%), toothache (23% and 15%), constipation (17%), myalgia (17%), rash (14% and 27%), dizziness (15%), and nausea (10%).
  • Postmarketing experience reported in CRYSVITA-treated pediatric XLH patients: blood phosphorus increased.

Adult Patients

  • Adverse reactions reported in more than 5% of CRYSVITA-treated adult XLH patients and in at least 2 patients more than placebo in one study are: back pain (15%), headache (13%), tooth infection (13%), restless legs syndrome (12%), vitamin D decreased (12%), dizziness (10%), constipation (9%), muscle spasms (7%), and blood phosphorus increased (6%).
  • Spinal stenosis is prevalent in adults with XLH, and spinal cord compression has been reported. It is unknown if CRYSVITA therapy exacerbates spinal stenosis or spinal cord compression.

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 at 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. CRYSVITA (burosumab-twza). US Prescribing Information. Kyowa Kirin, Inc.; March 2023. 2. Imel EA, Glorieux FH, Whyte MP, et al. Burosumab versus conventional therapy in children with X-linked hypophosphataemia: a randomised, active-controlled, open-label, phase 3 trial. Lancet. 2019;393(10189):2416-2427. doi:10.1016/S0140-6736(19)30654-3. 3. Data on file. 301 CSR. Ultragenyx Pharmaceutical Inc.; 2018. 4. UX023-CL301 Picture Book 2019. 5. Ruppe MD. X-linked hypophosphatemia. In: Adam MP, Everman DB, Mirzaa GM, et al., eds. GeneReviews®. Seattle (WA): University of Washington, Seattle; February 9, 2012. Updated April 13, 2017. https://www.ncbi.nlm.nih.gov/books/NBK83985/ 6. Onufrak SJ, Bellasi A, Cardarelli F, et al. Investigation of gender heterogeneity in the associations of serum phosphorus with incident coronary artery disease and all-cause mortality. Am J Epidemiol. 2008;169(1):67-77. doi:10.1093/aje/kwn285 7. Whyte MP, Fujita KP, Moseley S, Thompson DD, McAlister WH. Validation of a novel scoring system for changes in skeletal manifestations of hypophosphatasia in newborns, infants, and children: the Radiographic Global Impression of Change scale. J Bone Miner Res. 2018;33(5):868-874. doi:10.1002/jbmr.3377 8. Thacher TD, Pettifor JM, Tebben PJ, et al. Rickets severity predicts clinical outcomes in children with X-linked hypophosphatemia: utility of the radiographic Rickets Severity Score. Bone. 2019;122:76-81. doi:10.1016/j.bone.2019.02.010