atraumatic lucencies extending across one cortex. There were 52% of patients who had either active (unhealed) fractures (12%) or active pseudofractures (47%) at baseline. The active fractures and pseudofractures were predominantly located in the femurs, tibia/fibula, and metatarsals of the feet. Assessment of these active fracture/pseudofracture sites at week 24 demonstrated a higher rate of complete healing in the CRYSVITA group compared to placebo as shown in Table 8. During treatment through week 24, a total of 6 new fractures or pseudofractures appeared in 68 patients receiving CRYSVITA, compared to 8 new abnormalities in 66 patients receiving placebo.
Table 8:Comparison of Fracture Healing with CRYSVITA vs Placebo in Study 3
Active Fractures Active Pseudofractures Total Fractures
Placebo
n (%) CRYSVITA
n (%) Placebo
n (%) CRYSVITA
n (%) Placebo
n (%) CRYSVITA
n (%)
No. of fractures at baseline 13 14 78 51 91 65
Healed at week 24 0 (0%) 7 (50%) 7 (9%) 21 (41%) 7 (8%) 28 (43%)
Bone Histomorphometry
In Study 4, after 48 weeks of treatment, healing of osteomalacia was observed in ten patients as demonstrated by decreases in Osteoid volume/Bone volume (OV/BV) from a mean (SD) score of 26% (12.4) at baseline to 11% (6.5), a change of -57%. Osteoid thickness (O.Th) declined in eleven patients from a mean (SD) of 17 (4.1) micrometers to 12 (3.1) micrometers, a change of -33%. Mineralization lag time (MLt) declined in 6 patients from a mean (SD) of 594 (675) days to 156 (77) days, a change of -74%.
16 HOW SUPPLIED/STORAGE AND HANDLING
CRYSVITA (burosumab-twza) injection for subcutaneous administration is supplied as a sterile, preservative-free, clear to slightly opalescent and colorless to pale brown-yellow solution. The product is available as one single-dose vial per carton in the following strengths:
10 mg/mL (NDC# 69794-102-01)
20 mg/mL (NDC# 69794-203-01)
30 mg/mL (NDC# 69794-304-01)
CRYSVITA vials must be stored in the original carton until the time of use under refrigerated conditions at 36°F to 46°F (2°C to 8°C). Keep CRYSVITA vial in the original carton to protect from light until time of use.
Do not freeze or shake CRYSVITA.
Do not use CRYSVITA beyond the expiration date stamped on the carton.
CRYSVITA vials are single-dose only. Discard any unused product.
17 PATIENT COUNSELING INFORMATION
Hypersensitivity Reactions
Advise patients that CRYSVITA may cause hypersensitivity events such as rash, injection site rash and urticaria. Instruct the patients to contact their physician if such reactions occur [see Adverse Reactions (6.1)].
Injection Site Reactions
Inform patients that injection site reactions (e.g. erythema, rash, swelling, bruising, pain, pruritus, urticaria, and hematoma) have occurred at the site of CRYSVITA injection. Instruct the patients to contact their physician if such reactions occur [see Adverse Reactions (6.1)].
Restless Leg Syndrome
Advise patients that CRYSVITA can induce RLS or worsen the symptoms of existing RLS. Instruct the patients to contact their physician if such a reaction occurs [see Adverse Reactions (6.1)].
Pregnancy
Report pregnancies to the Ultragenyx Adverse Event reporting line at 1-888-756-8657 [see Use in Specific Populations (8.1)].
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