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CRYSVITA® (burosumab-twza) injection 10, 20, 30 mg/mL

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Cora, a person living with XLH, smiling

Cora,
on CRYSVITA since 2018

CRYSVITA was effective in treating children with XLH1

A phase 3 study showed that CRYSVITA1:

Two bones showing abnormalities

Helped heal rickets and reduce rickets severity

A ruler rotated at a 45-degree angle with an arrow pointing up

Increased growth

Phosphate element, as shown in the periodic table

Increased and sustained serum phosphorus levels

Study design

Study 1 | Phase 3, randomized1-3

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.

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
(n=32)

Weeks 0-64

Open-label treatment period

Primary endpoint2:

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

Secondary endpoints3:

  • 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

As per the statistical analysis plan, the primary assessment time for growth-related endpoints and RGI-C long leg score was week 64. For other secondary endpoints, the primary assessment time was week 40. Because of the small sample size, no multiplicity was adjusted for the secondary endpoints.

Safety endpoint3:

  • Number of patients with adverse events (AEs) and serious adverse events (SAEs)
Patient demographics and 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, mg/dL (SD) 2.4 (0.26)
Radiographic evidence of rickets, % 100%
Prior therapy of oral phosphate and active vitamin D analogs, % 100%
Mean duration of prior therapy, years (SD) 4 (3.1)
Patient demographics and disease burden at baseline1,3

Category

Mean age, years (range)

6.3 (1-12)

Category

Male, n (%)

27 (44%)

Category

Mean serum phosphorus, mg/dL (SD)

2.4 (0.26)

Category

Radiographic evidence of rickets, %

100%

Category

Prior therapy of oral phosphate and active vitamin D analogs, %

100%

Category

Mean duration of prior therapy, years (SD)

4 (3.1)

No pediatric patients discontinued CRYSVITA treatment in the study.1

Study 2 | Phase 2, randomized1,4

CRYSVITA was studied in a 64-week open-label phase 2 study (Study 2) in 52 children with XLH between 5 and 12 years of age. Study 2 compared treatment with CRYSVITA administered every 2 weeks (n=26) vs treatment every 4 weeks (n=26). Following an initial 16-week dose titration phase, patients completed 48 weeks of treatment with CRYSVITA. Patients randomized to CRYSVITA every 2 weeks received a mean dose of 1.05 mg/kg (range 0.4-2.0 mg/kg) at week 64.

Primary endpoint4:

  • Change from baseline total RSS score at week 40 and week 64

Secondary endpoints4:

  • Assessment of RGI-C global score at week 40 and week 64
  • Changes in serum phosphorus levels, TmP/GFR, and serum ALP activity
  • Change from baseline to week 64 in standing height z-score

Safety endpoint4:

  • Number of patients with AEs and SAEs
Study 3 | Phase 21,5

CRYSVITA was studied in a 64-week open-label phase 2 study (Study 3) in 13 children with XLH between 1 and 4 years of age. Patients received CRYSVITA every 2 weeks. At week 40, the mean dose was 0.90 mg/kg (range, 0.8-1.2 mg/kg).

Co-primary endpoint5:

  • Safety and change from baseline to week 40 in fasting serum phosphorus concentration

Secondary endpoints5:

  • Change from baseline total RSS score and RGI-C score
  • Change from baseline in lower limb deformity score
  • Change from baseline in serum ALP activity

ALP=alkaline phosphatase; TmP/GFR=tubular maximum phosphate reabsorption per glomerular filtration rate.

Rickets healing

PRIMARY AND SECONDARY ENDPOINTS

CRYSVITA improved healing of rickets at week 40 vs conventional therapy in children with XLH1,2

Mean Radiographic Global Impression of Change (RGI-C) in rickets severity1,2*

Bar graph of mean Radiographic Global Impression of Change (RGI-C) scores in rickets severity at week 40 and week 64 for conventional therapy and CRYSVITA. Week 40 values are 0.8 for conventional therapy and 1.9 for CRYSVITA. Week 64 values are 1.0 for conventional therapy and 2.1 for CRYSVITA.
Show description

Chart showing the mean RGI-C score in rickets severity between CRYSVITA® (burosumab-twza) and conventional therapy.

  • Week 40 (primary endpoint) – conventional therapy +0.8, CRYSVITA +1.9
  • Week 64 (secondary endpoint) – conventional therapy +1.0, CRYSVITA +2.1

Improved RGI-C at week 40 with CRYSVITA indicated healing of rickets, which was maintained at week 64.1,2

Primary endpoint

LS mean (95% CI) RGI-C score at week 401,2:

  • CRYSVITA: +1.9 (+1.70, +2.14)
  • Conventional therapy: +0.8 (+0.56, +0.99)

Secondary endpoint

LS mean (95% CI) RGI-C score at week 641,2:

  • CRYSVITA: +2.1 (+1.91, +2.20)
  • Conventional therapy: +1.0 (+0.77, +1.30)

*The estimates of LS mean and 95% CI 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.1,6

ANCOVA=analysis of covariance; CI=confidence interval; GEE=generalized estimating equation; LS=least squares.

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).1,5,12

  • RGI-C scores assess changes in the severity of rickets using the disease-specific qualitative RGI-C scoring system5,12
  • RGI-C scores are assigned by 3 independent experts blinded to treatment and patient2,4,5
  • An RGI-C score of +2.0 indicates substantial healing of rickets1,12

RGI-C scoring scale5,12

RGI-C scoring scale ranging from negative 3.0 to positive 3.0, labeled as follows: negative 3.0 severe worsening; negative 2.0 moderate worsening; negative 1.0 minimal worsening; 0 no change; positive 1.0 minimal healing; positive 2.0 substantial healing; positive 3.0 complete or near complete healing.
Show description

A figure showing the RGI-C 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 with XLH achieve substantial healing of rickets vs conventional therapy1,2

Percentage of patients who achieved substantial healing of rickets (RGI-C score ≥+2.0) at week 402

A bent knee joint with surrounding tissue with a partial yellow circle around it

72%

(21 out of 29)

of patients
on CRYSVITA

A versus symbol
A bent knee joint with surrounding tissue with a partial grey circle around it

6%

(2 out of 32)

of patients on
conventional therapy

At week 40, more patients receiving CRYSVITA achieved substantial healing of rickets (RGI-C score of ≥+2.0) compared with patients receiving conventional therapy2†:

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

†These results were maintained at week 64.1

Patients on CRYSVITA in Studies 2 and 3 also experienced substantial healing of rickets.

  • Study 2: After 40 weeks, the mean RGI-C score was +1.7 in patients receiving CRYSVITA every 2 weeks. 69% (18 out of 26) of patients saw substantial healing of rickets (RGI-C score of ≥+2.0). These results were maintained at week 641
  • Study 3: After 40 weeks, the mean RGI-C score was +2.3 in patients receiving CRYSVITA. 100% (13 out of 13) of patients saw substantial healing of rickets (RGI-C score of ≥+2.0)1

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).1,5,12

  • RGI-C scores assess changes in the severity of rickets using the disease-specific qualitative RGI-C scoring system5,12
  • RGI-C scores are assigned by 3 independent experts blinded to treatment and patient2,4,5
  • An RGI-C score of +2.0 indicates substantial healing of rickets1,12

RGI-C scoring scale5,12

RGI-C scoring scale ranging from negative 3.0 to positive 3.0, labeled as follows: negative 3.0 severe worsening; negative 2.0 moderate worsening; negative 1.0 minimal worsening; 0 no change; positive 1.0 minimal healing; positive 2.0 substantial healing; positive 3.0 complete or near complete healing.
Show description

A figure showing the RGI-C 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 in children with XLH, which was maintained at week 641,3

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

Bar graphs showing mean total Thacher Rickets Severity Score (RSS) at baseline, week 40, and week 64 for conventional therapy and CRYSVITA. At baseline mean is 3.2. At week 40, conventional therapy is 2.5, and CRYSVITA is 1.1, reflecting 23 percent reduction for conventional therapy and 64 percent reduction for CRYSVITA. At week 64, conventional therapy is 2.2, and CRYSVITA is 1.0, reflecting 32 percent reduction from baseline for conventional therapy and 70 percent reduction for CRYSVITA
Show description

Chart showing the mean total RSS score change from baseline on CRYSVITA® (burosumab-twza).

  • 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)

A reduced RSS score indicates improvement in rickets severity.1,7

In Studies 2 and 3 of children with XLH, CRYSVITA led to a reduction in rickets severity from baseline.

  • Study 2: Mean (SD) total RSS decreased from 1.9 (1.17) at baseline to 0.8 (0.55) at week 40 in patients receiving CRYSVITA once every 2 weeks1,8
  • Study 3: Mean (SD) total RSS decreased from 2.9 (1.37) at baseline to 1.2 (0.52) at week 40 in patients receiving CRYSVITA1,9

‡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 The baseline RSS score was 3.2 for both the CRYSVITA and conventional therapy arms.2

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,1,2,5,13

  • It is a predefined scale that evaluates specific abnormalities in the wrists and knees1,2,5,13
    • Total points progress in half-point increments from 0-10: wrists (0-4) plus knees (0-6)
  • In clinical trials, RSS is assigned by an independent expert blinded to treatment, treatment duration, and radiographic sequence2,4,5
  • Higher scores indicate a more severe state of rickets, and a reduction in RSS indicates an improvement in severity1,2,5,13

An example of RSS scores from knee X-rays2

Knee x-ray image example labeled RSS 1.0 on the Thacher Rickets Severity Score scale; Knee x-ray image example labeled RSS 1.5 on the Thacher Rickets Severity Score scale
Show description

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

Secondary endpoint

CRYSVITA maintained greater improvement in lower extremity skeletal abnormalities in children with XLH at week 641

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

X-ray images showing lower legs at baseline and at week 64 with CRYSVITA treatment;X-ray images showing lower legs at baseline and at week 64 with conventional therapy
Show description

X-ray images of 2 pairs of long leg radiographs at baseline and after 64 weeks of treatment with CRYSVITA® (burosumab-twza) or conventional therapy.

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

In Study 3 of children with XLH, CRYSVITA helped to improve lower extremity skeletal abnormalities among patients.

  • Study 3: In patients receiving CRYSVITA, the mean (SE) change in lower extremity skeletal abnormalities as assessed by RGI-C in standing long leg radiographs was +1.3 (0.14) at week 401

§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.1,3

Growth increase

Secondary endpoint

CRYSVITA increased growth vs conventional therapy in children with XLH through week 641,2

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

Line graph showing least squares mean increase in height z-score from baseline to week 64 of 0.17 with CRYSVITA and 0.02 with conventional therapy in children with XLH.
Show description

A graph showing the change from baseline in height z-scores with CRYSVITA® (burosumab-twza) vs conventional therapy.

  • Week 64 – CRYSVITA +0.17, conventional therapy +0.02

At 64 weeks, the following improvements were seen in mean (SD) standing height z-score1:

  • 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)

In Study 2 of children with XLH, CRYSVITA helped increase growth among patients.

  • Study 2: In patients receiving CRYSVITA every 2 weeks, the mean (SD) standing height z-score increased from -1.72 (1.03) at baseline to -1.54 (1.13) at 64 weeks1

||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.1,2

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 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 and ALP

Secondary endpoint

CRYSVITA increased and maintained serum phosphorus levels in children with XLH through week 641,6

Mean serum phosphorus levels in children receiving CRYSVITA or conventional therapy change from baseline (mg/dL)1,6

Line graph showing mean serum phosphorus levels in mg/dL from baseline through week 64 in children receiving CRYSVITA or conventional therapy. CRYSVITA increases from 2.4 mg/dL at baseline to 3.6 mg/dL at week 4, 3.2 mg/dL at week 24, and 3.3 mg/dL at weeks 40 and 64. Conventional therapy measures 2.3 mg/dL at baseline, 2.5 mg/dL at week 4, 2.6 mg/dL at week 24, 2.5 mg/dL at week 40, and 2.5 mg/dL at week 64. A dashed line indicates the lower limit of normal at 3.2 mg/dL.
Show description

A graph showing the mean serum phosphorus levels in children receiving CRYSVITA® (burosumab-twza) 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 levels 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 641
  • An increase in serum phosphorus levels above the lower limit of normal (LLN) was observed with CRYSVITA at week 1. Increased levels were maintained through week 641,3

In Studies 2 and 3 of children with XLH, CRYSVITA increased and maintained serum phosphorus levels within the normal range.#

  • Study 2: In patients receiving CRYSVITA every 2 weeks, the mean (SD) serum phosphorus levels increased from 2.4 (0.40) mg/dL at baseline to 3.3 (0.40) mg/dL at week 40 and to 3.4 (0.45) mg/dL at week 641
  • Study 3: In patients receiving CRYSVITA, the mean (SD) serum phosphorus levels increased from 2.5 (0.28) mg/dL at baseline to 3.5 (0.49) mg/dL at week 401

Serum ALP activity:

  • For Study 1, mean (SD) total serum ALP 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 641

In Studies 2 and 3 of children with XLH, CRYSVITA decreased serum ALP activity among patients.

  • Study 2: In patients receiving CRYSVITA every 2 weeks, the mean (SD) serum total ALP activity decreased from 462 (110) U/L at baseline to 354 (73) U/L at week 64 (mean change: -23%)1
  • Study 3: In patients receiving CRYSVITA, the mean (SD) serum total ALP activity decreased from 549 (194) U/L at baseline to 335 (88) U/L at week 40 (mean change: -36%)1

Mean serum phosphorus level (mg/dL). LLN is 3.2 mg/dL.1

#Normal levels of serum phosphorus for children aged 1-12 years range from 3.2 mg/dL to 6.1 mg/dL. Note that the normal levels of serum phosphorus vary by age and sex.3,12

Safety

Clinical safety profile of CRYSVITA 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%
Most common adverse reactions (≥10%) in patients treated with CRYSVITA observed in Study 11**

Adverse reaction

Pyrexia

CRYSVITA
(n=29) accordion-arrow
55%
Conventional therapy
(n=32) accordion-arrow
19%

Adverse reaction

Injection site reaction††

CRYSVITA
(n=29) accordion-arrow
52%
Conventional therapy
(n=32) accordion-arrow
0%

Adverse reaction

Cough‡‡

CRYSVITA
(n=29) accordion-arrow
52%
Conventional therapy
(n=32) accordion-arrow
19%

Adverse reaction

Vomiting

CRYSVITA
(n=29) accordion-arrow
41%
Conventional therapy
(n=32) accordion-arrow
25%

Adverse reaction

Pain in extremity

CRYSVITA
(n=29) accordion-arrow
38%
Conventional therapy
(n=32) accordion-arrow
31%

Adverse reaction

Headache

CRYSVITA
(n=29) accordion-arrow
34%
Conventional therapy
(n=32) accordion-arrow
19%

Adverse reaction

Tooth abscess§§

CRYSVITA
(n=29) accordion-arrow
34%
Conventional therapy
(n=32) accordion-arrow
13%

Adverse reaction

Dental caries

CRYSVITA
(n=29) accordion-arrow
31%
Conventional therapy
(n=32) accordion-arrow
6%

Adverse reaction

Diarrhea

CRYSVITA
(n=29) accordion-arrow
24%
Conventional therapy
(n=32) accordion-arrow
6%

Adverse reaction

Vitamin D decreased||||

CRYSVITA
(n=29) accordion-arrow
24%
Conventional therapy
(n=32) accordion-arrow
3%

Adverse reaction

Constipation

CRYSVITA
(n=29) accordion-arrow
17%
Conventional therapy
(n=32) accordion-arrow
0%

Adverse reaction

Rash¶¶

CRYSVITA
(n=29) accordion-arrow
14%
Conventional therapy
(n=32) accordion-arrow
6%

Adverse reaction

Nausea

CRYSVITA
(n=29) accordion-arrow
10%
Conventional therapy
(n=32) accordion-arrow
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:

A silhouette of a person with multiple circles on their body

Hypersensitivity reactions

In Study 1 (N=29 for CRYSVITA arm), the most frequent hypersensitivity reactions were rash (10%), injection site rash (10%), and injection site urticaria (7%).1

In Studies 2 and 3 (N=65), the most frequent hypersensitivity reactions were rash (22%), injection site rash (6%), and urticaria (5%).1

Phosphate element, as shown in the periodic table

Hyperphosphatemia

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

A syringe

Injection site reaction

In Study 1 (N=29 for CRYSVITA arm), 52% of the patients had a local injection site reaction (eg, injection site urticaria, erythema, rash, swelling, bruising, pain, pruritus, and hematoma) at the site of CRYSVITA injection.1

In Studies 2 and 3 (N=65), approximately 58% of the patients had a local injection site reaction at the site of CRYSVITA 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

Cora, a person living with XLH, standing and smiling while holding a hula hoop

Cora,

on CRYSVITA since 2018

Want to learn more about starting your pediatric patients with XLH on CRYSVITA?

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REQUEST A REP
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.

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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.

Hypercalcemia

  • Increases in serum calcium have been reported in patients treated with CRYSVITA. Patients with risk factors such as pre-existing hyperparathyroidism, prolonged immobilization, dehydration, hypervitaminosis D, or renal impairment, are at higher risk of hypercalcemia. Monitor these patients for serum calcium and parathyroid hormone levels before and during CRYSVITA treatment for moderate to severe hypercalcemia. In patients with moderate to severe hypercalcemia, CRYSVITA should not be administered until hypercalcemia is adequately managed.

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%).

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.

Hypercalcemia

  • Increases in serum calcium have been reported in patients treated with CRYSVITA. Patients with risk factors such as pre-existing hyperparathyroidism, prolonged immobilization, dehydration, hypervitaminosis D, or renal impairment, are at higher risk of hypercalcemia. Monitor these patients for serum calcium and parathyroid hormone levels before and during CRYSVITA treatment for moderate to severe hypercalcemia. In patients with moderate to severe hypercalcemia, CRYSVITA should not be administered until hypercalcemia is adequately managed.

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%).

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; April 2026. 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. 3. Data on file. 301-Week 64 CSR. Ultragenyx Pharmaceutical Inc.; 2019. 4. Carpenter TO, Whyte MP, Imel EA, et al. Burosumab therapy in children with X-linked hypophosphatemia. N Engl J Med. 2018;378(21):1987-1998. doi:10.1056/NEJMoa1714641 5. Whyte MP, Carpenter TO, Gottesman GS, et al. Efficacy and safety of burosumab in children aged 1-4 years with X-linked hypophosphataemia: a multicentre, open-label, phase 2 trial. Lancet Diabetes Endocrinol. 2019;7(3):189-199. 6. Data on file. 301-Week 40 CSR. Ultragenyx Pharmaceutical Inc.; 2018. 7. Asfotase Alfa (Strensiq). Ottawa (ON): Canadian Agency for Drugs and Technologies in Health; Appendix 6, Validity of outcome measures. April 2017. Accessed September 3, 2025. https://www.ncbi.nlm.nih.gov/books/NBK476053/ 8. Data on file. UX023-CL201 CSR. Ultragenyx Pharmaceutical Inc.; 2019. 9. Data on file. UX023-CL205 CSR. Ultragenyx Pharmaceutical Inc.; 2019. 10. UX023-CL301 Picture Book; 2019. 11. Koek WNH, Campos-Obando N, van der Eerden BCJ, et al. Age dependent sex differences in calcium and phosphate homeostasis. Endocr Connect. 2021;10(3):273-282. doi:10.1530/EC-20-0509 12. Lim R, Shailam R, Hulett 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. doi:10.1016/j.bone.2021.115964 13. Thacher TD, Pettifor JM, Tebben PJ, Creo AL, Skrinar A, Mao M, 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

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COMM-US-CRY-0777 June 2026