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A young girl standing with her hands on her hips.

Meet Cora,a real
CRYSVITA patient

CRYSVITA was effective in treating XLH1

A phase 3 study showed that CRYSVITA:1

Illustration of a pair of parallel bones that bend inward, with a transparent orange circle in the top corner

Helped heal rickets and reduce rickets severity

Illustration of a ruler with an arrow running alongside it pointing up, and a transparent orange circle in the top corner

Increased growth

Illustration of phosphorus from the periodic table, with a transparent orange circle in the top corner

Increased and sustained serum phosphorus levels

Study Design

Study 1 | Phase 3, randomized1

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

Group A

Crysvita

Mean dose of 0.90 mg/kg (range 0.8-1.2 mg/kg) every 2 weeks (n=29)

Group B

Conventional therapy

(Oral phosphate + vitamin D supplements) every 2 weeks (n=32)

Weeks 0-64

Open-label treatment period

Primary endpoint:2

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

Secondary endpoints:3

  • 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
  • Fasting serum phosphorus levels
  • Alkaline phosphatase (ALP) activity
  • Assessment of RGI-C at week 64
  • Proportion of patients with mean RGI-C score 2.0

Safety endpoint:3

  • Number of patients with adverse events (AEs), serious adverse events (SAEs), and AEs leading to discontinuation

Disease burden at baseline1,3

Category Study 1 (n=61)
Mean age, years (range) 6.3 (1-12)
Male, n (%) 27 (44%)
Mean serum phosphorus (SD) 2.4 (0.26) mg/dL
Radiographic evidence of rickets, % 100%
Prior therapy, including oral phosphate and active vitamin D analogs, % 100%
Mean duration of prior therapy, years 4
Category

Mean age, years (range)
Study 1 (n=61)
6.3 (1-12)
Category

Male, n (%)
Study 1 (n=61)
27 (44%)
Category

Mean serum phosphorus (SD)
Study 1 (n=61)
2.4 (0.26) mg/dL
Category

Radiographic evidence of rickets, %
Study 1 (n=61)
100%
Category

Prior therapy, including oral phosphate and active vitamin D analogs, %
Study 1 (n=61)
100%
Category

Mean duration of prior therapy, years
Study 1 (n=61)
4

No pediatric patients discontinued CRYSVITA treatment in the study.1

SD=standard deviation.

CRYSVITA was evaluated in 2 other phase 2 studies. To learn more about Study 2 and Study 3, please see full Prescribing Information.1

Rickets healing

Primary endpoint

CRYSVITA improved healing of rickets at week 40 when compared with conventional therapy1,2

Mean radiographic global impression of change (RGI-C) in rickets severity1,2,*

button to expand image A bar graph showing the mean radiographic global impression of change in rickets severity between CRYSVITA and conventional therapy.
Show description

Chart showing the mean radiographic global impression of change in rickets severity between CRYSVITA and conventional therapy.

  • Week 40 (Primary Endpoint) – conventional therapy 0.8, CRYSVITA 1.9 (P<0.0001)

Week 64 (Secondary Endpoint) – conventional therapy 1.0, CRYSVITA 2.1 (P<0.0001)

Week 40 (primary endpoint):1

  • LS mean (95% CI) RGI-C score in patients treated with CRYSVITA was +1.9 (+1.70, +2.14), indicating that healing of rickets occurred, compared with +0.8 (+0.56, +0.99) in the conventional therapy group

Week 64 (primary endpoint):1

  • Findings from week 40 were maintained at week 64 (LS mean [95% CI] RGI-C global score at week 64 was +2.1 (+1.91, +2.20) for CRYSVITA group and +1.0 (+0.77, +1.30) for conventional therapy group)

* 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. Two-sided 95% CIs were utilized. The P-values were reported as nominal. No adjustment on multiplicity was made.1,2

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.

The Radiographic Global Impression of Change (RGI-C)

RGI-C is a 7-point scoring method (-3=severe worsening; 0=no change; +3=near/complete healing).1,2,5

  • RGI-C scores assess changes in the severity of rickets using the disease-specific qualitative RGI-C scoring system5,6
  • RGI-C scores are assigned by 3 independent experts blinded to treatment and patient2
  • An RGI-C score of +2.0 indicates substantial healing of rickets1

RGI-C scoring scale1,2,5

button to expand image A figure showing the Radiographic Global Impression of Change scoring scale
Show description

A figure showing the Radiographic Global Impression of Change scoring scale

  • -3.0 – Severe worsening
  • -2.0 – Moderate worsening
  • -1.0 – Minimal worsening
  • 0 – No change
  • +1.0 – Minimal healing
  • +2.0 – Substantial healing
  • +3.0 – Complete or near complete

Secondary endpoint

CRYSVITA helped more patients achieve substantial healing of rickets compared with conventional therapy2

An icon of a knee with bones visible, outlined with an orange circle filled to 72%

72%

of patients receiving CRYSVITA achieved substantial healing† of rickets2

A versus symbol

P0.0001†

An icon of a knee with bones visible, outlined with a grey circle filled to 6%

6%

of patients receiving conventional therapy2

At week 40, more patients receiving CRYSVITA achieved substantial healing of rickets (RGI-C score of ≥+2.0) compared with patients receiving conventional therapy (P<0.0001):2,†

  • CRYSVITA arm: 72% (21 out of 29)
  • Conventional therapy arm: 6% (2 out of 32)

These results were maintained at week 64.2

†An RGI-C score of +2.0 indicates a substantial healing of rickets. Proportion of patients with mean RGI-C score ≥+2.0 was a secondary endpoint of the study. Two-sided P-value was based on a logistic regression model, which included treatment group and baseline age stratification factor as independent variables and baseline RSS score as a continuous covariate. The P-value was reported as nominal. No adjustment on multiplicity was made.2

RGI-C=Radiographic Global Impression of Change; RSS=Thacher Rickets Severity Score.

The Radiographic Global Impression of Change (RGI-C)

RGI-C is a 7-point scoring method (-3=severe worsening; 0=no change; +3=near/complete healing).1,2,5

  • RGI-C scores assess changes in the severity of rickets using the disease-specific qualitative RGI-C scoring system5,6
  • RGI-C scores are assigned by 3 independent experts blinded to treatment and patient2
  • An RGI-C score of +2.0 indicates substantial healing of rickets1

RGI-C scoring scale2,5

button to expand image A figure showing the Radiographic Global Impression of Change scoring scale
Show description

A figure showing the Radiographic Global Impression of Change scoring scale

  • -3.0 – Severe worsening
  • -2.0 – Moderate worsening
  • -1.0 – Minimal worsening
  • 0 – No change
  • +1.0 – Minimal healing
  • +2.0 – Substantial healing
  • +3.0 – Complete or near complete

Secondary endpoint

CRYSVITA led to a 64% reduction in rickets severity from baseline to week 40, which was maintained at week 641,3

Mean total Thacher Rickets Severity Score (RSS)1,3,‡

button to expand image A bar graph showing the mean total Thacher Rickets Severity score from baseline between CRYSVITA and conventional therapy.
Show description

Chart showing the mean total Thacher Rickets Severity score change from baseline.

  • Week 40 – Baseline 3.2, Conventional therapy 2.5 (23% reduction), CRYSVITA 1.1 (64% reduction)
  • Week 64 – Baseline 3.2, Conventional therapy 2.2 (32% reduction), CRYSVITA 1.0 (70% reduction)

Treatment every 2 weeks with CRYSVITA showed a 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

‡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; GEE=generalized estimation equation; LS=least squares; RSS=Thacher Rickets Severity Score.

The Thacher Rickets Severity Score (RSS)

RSS is a 10-point score for radiographs of wrists and knees to assess the degree of metaphyseal fraying and cupping and the proportion of the growth plate affected.1,2,7

  • It is a predefined scale that evaluates specific abnormalities in the wrists and knees1,2,7
    • Total points progress in half-point increments from 0-10: wrists (0-4) plus knees (0-6)
  • RSS is assigned by an independent expert blinded to treatment, treatment duration, and radiographic sequence2,7
  • Higher scores indicate a more severe state of rickets, and a reduction in RSS indicates an improvement in severity1,2,7

An example of RSS scores from knee X-rays6

button to expand image An X-ray image of a knee, captioned “RSS=1.0” and “RSS=1.5”
Show description

X-ray images of 2 knees, the first knee with an RSS score of 1.0, and the second knee of an RSS score of 1.5

Secondary endpoint

CRYSVITA maintained greater improvement in lower extremity skeletal abnormalities1

In Study 1, lower extremity skeletal abnormalities were assessed by RGI-C in standing long leg radiographs.

X-ray images of a pair of legs with skeletal abnormalities. The first image is at baseline, and the second image is after 64 weeks on CRYSVITA
X-ray images of a pair of legs with skeletal abnormalities. The first image is at baseline, and the second image is after 64 weeks on conventional therapy
Show description

X-ray images of two pairs of legs with skeletal abnormalities at baseline and after 64 weeks of treatment with CRYSVITA or conventional therapy.

Individual results may vary.

At week 64, CRYSVITA maintained greater improvement in lower extremity skeletal abnormalities compared with conventional therapy, as assessed by RGI-C (LS mean [SE]: +1.25 [0.17] vs +0.29 [0.12]).1,§

The radiographic examples show the following:1,4

  • A patient with XLH (female, 2.9 years of age) who received CRYSVITA every 2 weeks for 64 weeks
  • A patient (also female, 2.9 years of age) who continued on conventional therapy

§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

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

Growth increase

Secondary endpoint

CRYSVITA increased growth compared to conventional therapy1,2

Height z-scores with CRYSVITA every 2 weeks vs conventional therapy2,||

button to expand image A figure showing the height z-scores with CRYSVITA treatment every 2 weeks vs conventional therapy.
Show description

A figure showing the change from baseline in height z-scores with CRYSVITA treatment every 2 weeks vs conventional therapy.

  • Week 24 – CRYSVITA 0.13, Conventional therapy 0.05
  • Week 40 – CRYSVITA 0.15, Conventional therapy 0.03
  • Week 64 – CRYSVITA 0.17, Conventional therapy 0.02

At 64 weeks, the following improvements were seen in standing mean (SD) height z-score:1

  • In patients who received CRYSVITA every 2 weeks: z-score increased from -2.32 (1.17) at baseline to -2.11 (1.11)
  • In patients who received conventional therapy: z-score increased from -2.05 (0.87) at baseline to -2.03 (0.83)

||The estimates of LS mean and SE 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

GEE=generalized estimation equation; LS=least squares; RSS=Thacher Rickets Severity Score; SD=standard deviation; SE=standard error.

The standing height z-score2,3

  • 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

Change in serum phosphorus levels

Secondary endpoint

CRYSVITA increased and maintained serum phosphorus levels1

Mean serum phosphorus levels in children receiving CRYSVITA or conventional therapy1,

button to expand image A figure showing the mean serum phosphorus levels in children receiving CRYSVITA or conventional therapy.
Show description

A figure showing the mean serum phosphorus levels in children receiving CRYSVITA or conventional therapy.

  • Week 0 – CRYSVITA 2.4 mg/dL, Conventional therapy 2.3 mg/dL
  • Week 4 – CRYSVITA 3.6 mg/dL, Conventional therapy 2.5 mg/dL
  • Week 24 – CRYSVITA 3.2 mg/dL, Conventional therapy 2.6 mg/dL
  • Week 40 – CRYSVITA 3.3 mg/dL, Conventional therapy 2.5 mg/dL
  • Week 64 – CRYSVITA 3.3 mg/dL, Conventional therapy 2.5 mg/dL

Serum phosphorus:

  • In Study 1, CRYSVITA increased mean (SD) serum phosphorus levels from 2.4 (0.24) mg/dL at baseline to 3.3 (0.43) mg/dL at week 40 and to 3.3 (0.42) mg/dL at week 64. In the conventional therapy group, mean (SD) serum phosphorus concentrations increased from 2.3 (0.26) mg/dL at baseline to 2.5 (0.34) mg/dL at week 40 and to 2.5 (0.39) mg/dL at week 64.1
  • An increase in serum phosphorus levels compared with conventional therapy was observed with CRYSVITA at week 1 and maintained through week 64.1,3

Serum alkaline phosphatase activity:

  • For Study 1, mean (SD) total serum alkaline phosphatase activity decreased from 511 (125) U/L at baseline to 337 (86) U/L in the CRYSVITA group (mean change: -33%) and from 523 (154) U/L at baseline to 495 (182) U/L in the conventional therapy group (mean change: -5%) at week 64.1

Mean serum phosphorus level (mg/dL). 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.3,8

SD=standard deviation.

Safety

Safety endpoint

CRYSVITA clinical safety profile in children with XLH

Most common adverse reactions (≥10%) in patients treated with CRYSVITA observed in Study 11,**

Adverse Reaction Crysvita
(n-29) 		Conventional Therapy
(n=32)
Pyrexia 55% 19%
Injection site reaction†† 52% 0%
Cough‡‡ 52% 19%
Vomiting 41% 25%
Pain in extremity 38% 31%
Headache 34% 19%
Tooth abscess§§ 34% 13%
Dental caries 31% 6%
Diarrhea 24% 6%
Vitamin D decreased|||| 24% 3%
Constipation 17% 0%
Rash¶¶ 14% 6%
Nausea 10% 3%
Adverse Reaction

Pyrexia
Crysvita
(n-29)
55%
Conventional Therapy
(n=32)
19%
Adverse Reaction

Injection site reaction††
Crysvita
(n-29)
52%
Conventional Therapy
(n=32)
0%
Adverse Reaction

Cough‡‡
Crysvita
(n-29)
52%
Conventional Therapy
(n=32)
19%
Adverse Reaction

Vomiting
Crysvita
(n-29)
41%
Conventional Therapy
(n=32)
25%
Adverse Reaction

Pain in extremity
Crysvita
(n-29)
55%
Conventional Therapy
(n=32)
31%
Adverse Reaction

Headache
Crysvita
(n-29)
34%
Conventional Therapy
(n=32)
19%
Adverse Reaction

Tooth abscess§§
Crysvita
(n-29)
34%
Conventional Therapy
(n=32)
13%
Adverse Reaction

Dental caries
Crysvita
(n-29)
31%
Conventional Therapy
(n=32)
6%
Adverse Reaction

Diarrhea
Crysvita
(n-29)
24%
Conventional Therapy
(n=32)
6%
Adverse Reaction

Vitamin D decreased||||
Crysvita
(n-29)
24%
Conventional Therapy
(n=32)
3%
Adverse Reaction

Constipation
Crysvita
(n-29)
17%
Conventional Therapy
(n=32)
0%
Adverse Reaction

Rash¶¶
Crysvita
(n-29)
14%
Conventional Therapy
(n=32)
6%
Adverse Reaction

Nausea
Crysvita
(n-29)
10%
Conventional Therapy
(n=32)
3%

n=total number of patients who received at least 1 dose of CRYSVITA or conventional therapy.

**≥10% in the CRYSVITA group that also occurred at a higher frequency than the conventional therapy group.1

††Injection site reaction includes: injection site reaction, injection site erythema, injection site pruritus, injection site swelling, injection site pain, injection site rash, injection site bruising, injection site discoloration, injection site discomfort, injection site hematoma, injection site hemorrhage, injection site induration, injection site macule, and injection site urticaria.1,

‡‡Cough includes: cough and productive cough.1,

§§Tooth abscess includes: tooth abscess, tooth infection, and toothache.1,

||||Vitamin D decreased includes: vitamin D deficiency, blood 25-hydroxycholecalciferol decreased, and vitamin D decreased.1,

¶¶Rash includes: rash, rash pruritic, rash maculopapular, rash erythematous, rash generalized, and rash pustular.1,

Adverse reactions:

Outline of a person with grey circles of different sizes on their body

Hypersensitivity reactions

The most frequent hypersensitivity reactions in the CRYSVITA arm were rash (10%), injection site rash (10%), and injection site urticaria (7%).1

Illustration of phosphorus from the periodic table

Hyperphosphatemia

In pediatric studies, there were no events of hyperphosphatemia reported.1

Illustration of a syringe

Injection site reaction

Fifty-two percent of patients in the CRYSVITA arm had a local injection site reaction (e.g., injection site urticaria, erythema, rash, swelling, bruising, pain, pruritus, and hematoma) at the site of injection. Injection site reactions were generally mild in severity, occurred within 1 day of injection, lasted approximately 1 to 3 days, required no treatment, and resolved in almost all instances.1

Illustration of an antibody

Immunogenicity

As with all therapeutic proteins, there is potential for immunogenicity. The detection of antibody formation is highly dependent on the sensitivity and specificity of the assay. Additionally, the observed incidence of antibody (including neutralizing antibody) positivity in an assay may be influenced by several factors, including assay methodology, sample handling, timing of sample collection, concomitant medications, and underlying disease. For these reasons, comparison of the incidence of antibodies to CRYSVITA in the studies described in this website with the incidence of antibodies in other studies or to other products may be misleading.1

In XLH clinical studies, none (0/13) of the 1- to 4-year-old patients, 19% (10/52) of the 5- to 12-year-old patients, and 15% (20/131) of the adult patients tested positive for anti-drug antibodies (ADA) after receiving CRYSVITA. Among these, three 5- to 12-year-old patients tested positive for neutralizing antibodies. The presence of ADA was not associated with clinically relevant changes in pharmacokinetics, pharmacodynamics, efficacy, and safety of burosumab in patients with XLH.1

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CRYSVITA patient

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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.

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 COUNSELLING 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 COUNSELLING 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.

Reference:

  • 1. CRYSVITA (burosumab-twza). US Prescribing Information. Kyowa Kirin, Inc. March 2023. 2. Imel EA, 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. 3. Data on file. 301 CSR. Ultragenyx Pharmaceutical Inc. 2018. 2022;17(1):30. 4. UX023-CL301 Picture Book. 2019. 5. Lim R, et al. Validation of the Radiographic Global Impression of Change (RGI-C) score to assess healing of rickets in pediatric X-linked hypophosphatemia (XLH). Bone. 2021;148:115964. 6. Whyte MP, et al. 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. 7. Thacher TD, 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. 8. Koek WNH, et al. Age-dependent sex differences in calcium and phosphate homeostasis. Endocr Connect. 2021;10(3):273-282.

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COMM-US-CRY-0076 | March 2025