Table 2.
Summary of differences or omissions in comparability exercise not precluding conclusion on biosimilarity
| Reference | Quality | Functional | PK | PD | Clinical (E/S) | Immunogenicity | Regulatory outcome in EU |
|---|---|---|---|---|---|---|---|
| Remsima (infliximab) | Decreased % of afucosylated species | Decreased ADCC activity | ✓ | Supportive | ✓ | ✓ | Approved |
| Cyltezo (adalimumab) | ✓ | ✓ | Initial PK study failed | Supportive | ✓ | ✓ | Approved |
| Hyrimoz (adalimumab) | ✓ | ✓ | Initial PK study failed | Supportive | ✓ | ✓ | Approved |
| Terrosa (teriparatide) | ✓ | ✓ | 90% CI of primary endpoints not covering unity | ✓ (PD analysis included in PK study) | NA | NA | Approved |
| Efgratin (pegfilgrastim) | ✓ | ✓ | PK study failed | ✓ | ✓ | ✓ | Withdrawn |
| Ziextenzo (pegfilgrastim) | ✓ | ✓ | Initial PK study failed | ✓ (PD analysis included in PK study) | ✓ | ✓ | Approved |
| Grastofil (filgrastim) | ✓ | ✓ | 90% CI of some endpoints not covering unity | ✓ | NA | NA | Approved |
| Semglee (insulin glargine) | ✓ | ✓ | ✓ | Formally failed PD (AUCGIR 0–30 h and GIR max) due to several patients with very low PD response | ✓ | ✓ | Approved |
| Ontruzant (trastuzumab) | ✓ | ✓ | ✓ | NA | Failure to meet upper equivalence limit for 1st EP of clinical S/E trial | ✓ | Approved |
| Kanjinti (trastuzumab) | ✓ | ✓ | ✓ | NA | Failure to meet upper equivalence limit for 1st EP of clinical S/E trial | ✓ | Approved |
| Rixathon (rituximab) | ✓ | ✓ | ✓ | Supportive | Pivotal trial: 1st EP: ORR was met, uncertainty regarding 2nd EPs PFS, OS | ✓ | Approved |
| Truxima (rituximab) | ✓ | ✓ | ✓ | Supportive | Pivotal trial: 1st EP: ACR20 was met, uncertainty regarding 2nd EPs PFS, OS | ✓ | Approved |
| Flixabi (infliximab) | ✓ | ✓ | ✓ | Supportive | ✓ | Slightly increased ADA | Approved |
| Benepali (etanercept) | ✓ | ✓ | ✓ | ✓ | ✓ | Reduced immunogenicity | Approved |
The table lists products for which a particular component of the comparability exercise raised a red flag during the assessment. Review of products for which an opinion was given between July 2012 and July 2019. References in all instances are the EPAR of the products
ACR20 improvement of 20% according to criteria of the American College of Rheumatology, ADA antidrug antibodies, ADCC antibody-dependent cell-mediated cytotoxicity, CI confidence interval, E efficacy, EP efficacy endpoint, GIR glucose infusion rate, NA not applicable, ORR objective response rate, PD pharmacodynamics, OS overall survival, PFS progression-free survival, PK pharmacokinetics, S safety, ✓ indicates results supporting biosimilarity