iness 7 (10) 4 (6)
Constipation 6 (9) 0 (0)
Blood phosphorus increased4 4 (6) 0 (0)
n = number of patients with an event; N = total number of patients who received at least one dose of CRYSVITA or placebo
1 Headache includes: headache, and head discomfort
2 Tooth infection includes: tooth abscess, and tooth infection
3 Vitamin D decreased includes: vitamin D deficiency, blood 25-hydroxycholecalciferol decreased, and vitamin D decreased
4 Blood phosphorus increased includes: blood phosphorus increased, and hyperphosphatemia
Hypersensitivity Reactions
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.
Hyperphosphatemia
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 two occasions). The hyperphosphatemia was managed with dose reduction. The dose for all patients meeting the protocol-specified criteria was reduced 50 percent. A single patient required a second dose reduction for continued hyperphosphatemia.
Injection Site Reactions (ISR)
In the double-blind period of Study 3, approximately 12% of patients in both the CRYSVITA and placebo treatment groups had a local reaction (e.g. 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.
Restless Leg Syndrome (RLS)
In the double-blind period of Study 3, approximately 12% of the CRYSVITA treatment group had worsening of baseline restless leg syndrome (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 one case, worsening baseline RLS led to drug discontinuation and subsequent resolution of the event.
Spinal Stenosis
Spinal stenosis is preva lent in adults with XLH and spinal cord compression has been reported. In the CRYSVITA phase 2 and phase 3 studies of adults with XLH (total N=176), a total of 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.
6.2 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 burosumab-twza in the studies described below with the incidence of antibodies in other studies or to other products may be misleading.
Pre-existing anti-drug antibodies (ADA) have bee |
