CRYSVITA® (burosumab-twza) safety was studied in 126 pediatric patients with XLH treated over 40 weeks

Adverse reactions related to taking CRYSVITA
Adverse reactions related to taking CRYSVITA

Adverse reactions

CRYSVITA was evaluated in 3 clinical studies of pediatric patients with XLH.

Study 1 was a Phase 3 randomized, open-label study in children aged 1 to 12 years in which patients (N=61) received CRYSVITA or conventional therapy for at least 64 weeks.

Adverse Reactions Reported in 10% or More of CRYSVITA-treated Pediatric Patients and With Higher Frequency Than Conventional Therapy–treated Patients in Study 1
Adverse
Reaction
CRYSVITA
(N=29) n (%)
Conventional Therapy
(N=32) n (%)
Pyrexia 16 (55) 6 (19)
Injection site reactiona 15 (52) 0 (0)
Coughb 15 (52) 6 (19)
Vomiting 12 (41) 8 (25)
Pain in extremity 11 (38) 10 (31)
Headache 10 (34) 6 (19)
Tooth abscessc 10 (34) 4 (13)
Dental caries 9 (31) 2 (6)
Diarrhea 7 (24) 2 (6)
Vitamin D decreasedd 7 (24) 1 (3)
Constipation 5 (17) 0 (0)
Rasha 4 (14) 2 (6)
Nausea 3 (10) 1 (3)

n, number of patients with an event; N, total number of patients who received at least 1 dose of CRYSVITA or conventional therapy.

  • aInjection 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.
  • bCough includes: cough and productive cough.
  • cTooth abscess includes: tooth abscess, tooth infection, and toothache.
  • dVitamin D decreased includes: vitamin D deficiency, blood 25-hydroxycholecalciferol decreased, and vitamin D decreased.
  • eRash includes: rash, rash pruritic, rash maculopapular, rash erythematous, rash generalized, and rash pustular.

Study 2 was a Phase 2 open-label study in children aged 5 to 12 years in which patients (N=52) received CRYSVITA for at least 64 weeks. Study 3 was a Phase 2 open-label study in children aged 1 to 4 years in which patients (N=13) received CRYSVITA for at least 40 weeks.1

Adverse Reactions Reported in More Than 10% of
Pediatric Patients Receiving CRYSVITA in Studies 2 and 3
Adverse
Reaction
Study 2
(N=52) n (%)
Study 3
(N=13) n (%)
Overall
(N=65) (%)
Headache 38 (73) 1 (8) 39 (60)
Injection site reactiona 35 (67) 3 (23) 38 (59)
Vomiting 25 (48) 6 (46) 31 (48)
Pyrexia 23 (44) 8 (62) 31 (48)
Pain in extremity 24 (46) 3 (23) 27 (42)
Vitamin D decreasedb 19 (37) 2 (15) 21 (32)
Rashc 14 (27) 1 (8) 15 (23)
Toothache 12 (23) 2 (15) 14 (22)
Myalgia 9 (17) 1 (8) 10 (15)
Tooth abscess 8 (15) 3 (23) 11 (17)
Dizzinessd 8 (15) 0 (0) 8 (12)

n, number of patients with an event; N, total number of patients who received at least one dose of CRYSVITA.

  • aInjection 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.
  • bVitamin D decreased includes: vitamin D deficiency, blood 25-hydroxycholecalciferol decreased, and vitamin D decreased.
  • cRash includes: rash, rash pruritic, rash maculopapular, and rash pustular.
  • dDizziness includes: dizziness, and dizziness exertional.
Incidence of hypersensitivity reactions related to taking CRYSVITA in children
Incidence of hypersensitivity reactions related to taking CRYSVITA in children

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

Incidence of hyperphosphatemia related to taking CRYSVITA in children
Incidence of hyperphosphatemia related to taking CRYSVITA in children

Hyperphosphatemia

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

Incidence of injection site reactions related to taking CRYSVITA in children
Incidence of injection site reactions related to taking CRYSVITA in children

Injection site reactions (ISRs)

In Study 1 (N=29 for CRYSVITA arm), 52% of the patients had a local injection site reaction (e.g., injection site urticaria, erythema, rash, swelling, bruising, pain, pruritus, and hematoma) at the site of CRYSVITA injection. In Studies 2 and 3 (N=65), approximately 58% of the patients had a local injection site reaction (e.g., injection site urticaria, erythema, rash, swelling, bruising, pain, pruritus, and hematoma) 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

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.

Pre-existing anti-drug antibodies (ADAs) have been detected in up to 10% of patients in clinical studies. ADA was not detected in patients who were antibody negative at the start of treatment. However, the assay used to measure ADA is subject to interference by serum CRYSVITA, possibly resulting in an underestimation of the incidence of antibody formation. Due to the limitation of the assay conditions, the potential clinical impact of antibodies to CRYSVITA is not known.

Reference
  1. CRYSVITA (burosumab-twza) US Prescribing Information; September 2019.