|Adverse Reactions Occurring in More Than 5% of CRYSVITA-treated Adult Patients and in at Least 2 Patients More Than With Placebo in Study 31|
(N=68) n (%)
(N=66) n (%)
|Back pain||10 (15)||6 (9)|
|Headachea||9 (13)||6 (9)|
|Tooth infectionb||9 (13)||6 (9)|
|Restless leg syndrome||8 (12)||5 (8)|
|Vitamin D decreasedc||8 (12)||3 (5)|
|Dizziness||7 (10)||4 (6)|
|Constipation||6 (9)||0 (0)|
|Blood phosphorus increasedd||4 (6)||0 (0)|
n, number of patients with an event; N, total number of patients who received at least 1 dose of CRYSVITA or placebo.
- aHeadache includes: headache and head discomfort.
- bTooth infection includes: tooth abscess and tooth infection.
- cVitamin D decreased includes: vitamin D deficiency, blood 25-hydroxycholecalciferol decreased, and vitamin D decreased.
- dBlood phosphorus increased includes: blood phosphorus increased and hyperphosphatemia.
In the double-blind period of Study 3, approximately 6% of patients in both the CRYSVITA and placebo treatment groups experienced a hypersensitivity event. The events were mild or moderate and did not require discontinuation.1
In the double-blind period of Study 3, 7% of patients in the CRYSVITA treatment group experienced hyperphosphatemia, meeting the protocol-specified criteria for dose reduction (either a single serum phosphorus greater than 5.0 mg/dL or serum phosphorus greater than 4.5 mg/dL [the upper limit of normal] on 2 occasions). The hyperphosphatemia was managed with dose reduction. The dose for all patients meeting the protocol-specified criteria was reduced by 50%. A single patient required a second dose reduction for continued hyperphosphatemia.1
In the double-blind period of Study 3, approximately 12% of patients in both the CRYSVITA and placebo treatment groups had a local reaction (eg, injection site reaction, erythema, rash, bruising, pain, pruritus, and hematoma) at the site of the 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
In the double-blind period of Study 3, approximately 12% of the CRYSVITA treatment group had worsening of baseline RLS or new onset RLS of mild to moderate severity; these events did not lead to dose discontinuation. Nonserious RLS has also been reported in other repeat-dose adult XLH studies; in 1 case, worsening baseline RLS led to drug discontinuation and subsequent resolution of the event.1
Spinal stenosis is prevalent in adults with XLH, and spinal cord compression has been reported. In the CRYSVITA phase 2 and phase 3 studies of adults with XLH (N=176), 6 patients underwent spinal surgery. Most of these cases appeared to involve progression of a pre-existing spinal stenosis. It is unknown if CRYSVITA therapy exacerbates spinal stenosis or spinal cord compression.1
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 (ADA) 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.
CRYSVITA (burosumab-twza) US Prescribing Information; September 2018.