The observed incidence of ADA (including neutralizing antibodies [Nab]) is highly dependent on the sensitivity and specificity of the assay. Differences in assay methods preclude meaningful comparisons of the incidence of ADA in the studies described below with the incidence of ADA in other studies, including those of ELELYSO or of other taliglucerase alfa products.
Anti-Drug Antibodies
In Trials 1, 2, and 3, a greater portion of ELELYSO-treated patients who developed ADA had hypersensitivity reactions compared to those who did not develop ADA [see Adverse Reactions (6.1) and Warnings and Precautions (5.1)].
In Trial 1 (treatment-naïve adults with Gaucher disease) [see Clinical Studies (14.1)], 17 (53%) of 32 ELELYSO-treated patients developed ADA. Additionally 2 (6%) patients tested positive for ADA at baseline prior to ELELYSO treatment.
In Trial 2 (treatment-naïve pediatric patients with Gaucher disease) [see Clinical Studies (14.1)], 2 (22%) of 9 Type 1 Gaucher disease ELELYSO-treated patients developed ADA. Additionally, 1 patient was ADA-positive prior to initiation of ELELYSO.
In Trial 3 (switched from imiglucerase to ELELYSO), of 31 ELELYSO-treated patients (26 adult and 5 pediatric patients) [see Clinical Studies (14.2)], 6 adults (23% of adult patients) developed ADA and no pediatric patient developed ADA. Additionally, 3 (10%) patients were ADA positive prior to initiation of ELELYSO.
There is insufficient information to characterize the ADA response to ELELYSO and the effects of ADA on pharmacokinetics, pharmacodynamics, or effectiveness of taliglucerase alfa products.
Neutralizing Antibodies
In Trials 1, 2 and 3 with a total number of 72 patients, 30 of the 31 ELELYSO-treated adult and pediatric patients who developed ADA or tested positive for ADA at baseline were evaluated for neutralizing activity of the ADA in the mannose receptor binding and enzyme activity assays.
- o
- Nineteen (63%) of the 30 patients had neutralizing antibodies (Nab) capable of inhibiting in vitro mannose receptor binding of ELELYSO.
- o
- Eight (42%) of these 19 patients had Nab capable of inhibiting the in vitro enzymatic activity of ELELYSO.
Although the effectiveness was numerically lower (less spleen and liver volume reduction) in ELELYSO-treated patients who developed Nab compared to those that did not develop Nab, the data were not sufficient to fully assess whether the observed Nab reduces effectiveness.
Other Antibodies
Nine (29%) of the 31 ELELYSO-treated adult and pediatric patients who developed ADA during treatment or tested positive for ADA at baseline also developed antibodies against plant-specific glycans in ELELYSO.