2. Acceptable changes in quality attributes of glycosylated biopharmaceuticals
Schiestl M, Stangler T, Torella C, et al. Nat Biotechnol. 2011;29(4):310-2.

3. Trial Design and Methods
Three major, marketed glycosylated biopharmaceuticals are reviewed, analyzing quality profiles of darbepoetin alfa, rituximab, and etanercept
Data revealed substantial alterations of the glycosylation profile for all tested products, most probably caused by changes in the manufacturing processes
Observed changes predicted the reference medicine, and therefore its approved biosimilar, do not alter the clinical profile and therefore are acceptable by the health authorities

4. Key Findings
Biologics are such complex glycoproteins that no one can duplicate them.
This study demonstrates that even the innovator product varies from batch-to-batch.

5. Faculty Commentary
This study provides a critical understanding of biologics without which we cannot understand biosimilars.
Results of this study can make the provider comfortable with the idea of using biosimilars, especially knowing approved biosimilars are tested to assure they are similar and perform similarly to innovator biologics.
While this study is informative about the variation in the drugs, it is not informative about what clinical implications those variations have.
The study does not tell us about the role of patient adherence and drug handling.

6. [Published online February 7, 2017]
The totality-of-the-evidence approach to the development and assessment of GP2015, a proposed etanercept biosimilar
Strand V, Girolomoni G, Schiestl M, et al. Curr Med Res Opin. 2017;7:1-11.
[Published online February 7, 2017]

7. Key Findings
Totality-of-the-evidence includes all analyses and performed trials used to approve the product and justify use of the biosimilar in all indications for which the reference medicine is approved.
Analytical data serve as the foundation of the overall comparability exercise and totality-of-the-evidence concept.
Biosimilars offer an opportunity to learn more about biologic medicines in general.

8. Faculty Commentary
This study highlights the extent to which biosimilars are studied to assure they will function the same as the innovator biologic.
This manuscript provides detailed descriptions of studies done on biosimilars, assuring providers and patients they can expect the same benefits from biosimilars as from innovator biologics.

9. Efficacy and safety of CT-P13 (biosimilar infliximab) in patients with rheumatoid arthritis: comparison between switching from reference infliximab to CT-P13 and continuing CT-P13 in the PLANETRA extension study
Yoo DH, Prodanovic N, Jaworski J, et al. Ann Rheum Dis. 2017;76(2):355–363.

10. Trial Design and Methods
Switching analysis of 302 patients with rheumatoid arthritis
Patients completed 54-week, PLANETRA study comparing CT-P13 with reference product (RP)
Switching from infliximab RP to CT-P13, or continuing CT-P13 in patients with RA for an additional 6 infusions
CT-P13 (3 mg/kg) administered intravenously every 8 weeks from weeks 62 to 102
Efficacy assessments at weeks 14, 30, 54, 78 and 102
Efficacy endpoints patients meeting ACR20, ACR50, and ACR70 criteria
RP, reference product; RA, rheumatoid arthritis; ACR, American College of Rheumatology.

11. Key Findings
Patients with RA received methotrexate, switched from RP to CT-P13 were not associated with any detrimental effects on efficacy, immunogenicity or safety.
CT-P13 remained efficacious and was well tolerated during a 2-year treatment period.
Data support long-term efficacy of CT-P13 in patients with RA.
RA, rheumatoid arthritis; RP, reference product.

12. Faculty Commentary
Patients on infliximab biosimilar seem to do as well as patients on infliximab.
This study shows patients who switch from reference infliximab to the biosimilar infliximab also do well.
Switching is unlikely to affect patients’ treatment outcome.
Data show CT-P13 biosimilar of infliximab does not have any unusual immunogenicity.
This study provides confidence that biosimilar infliximab is appropriate for use in patients who are currently doing well on reference infliximab.

13. The PROSIT-BIO cohort: A prospective observational study of patients with inflammatory bowel disease treated with infliximab biosimilar
Fiorino G, Manetti N, Armuzzi A, et al. Inflamm Bowel Dis. 2017;23(2):233–243.

14. Trial Design and Methods
Analysis of 547 patients previously diagnosed either as UC (n=234) or CD (n=313)
97 switched to CT-P13 from infliximab and followed for a mean of /- 2.8 months
311 patients were naive to anti-tumor necrosis factor alpha
139 had previous exposure to biologics
97 switched after a mean of 18 ± 14 infusions of infliximab
Efficacy was evaluated in 434 patients who received treatment for at least 8 weeks

15. Key Findings
Efficacy in terms of induction and/or maintaining of remission/response was high, approximately 90% at 24 weeks.
Patient Type
8 weeks
16 weeks
24 weeks
Naive
95.7%
86.4%
73.7%
Pre-exposed
97.2%
85.2%
62.2%
Switched
94.5%
90.8%
78.9%
Preliminary data on efficacy and safety of CT-P13 were in line with those of infliximab.

16. Faculty Commentary
Given this similarity of biosimilar to innovator, we should expect biosimilars to perform similarly to the innovator drug.
The main finding is the biosimilar gave similar clinical outcomes.
This study may make doctors and patients more comfortable with the idea of using a biosimilar.
Insurers may use these data to encourage greater use of biosimilars if doing so provides a cost saving.

17. Lai Z, La Noce A. RMD Open. 2016;2(1):e000154.
Key design considerations on comparative clinical efficacy studies for biosimilars: adalimumab as an example
Lai Z, La Noce A. RMD Open. 2016;2(1):e

18. Key Findings
Key study design elements vary among 9 phase 3 studies for 8 adalimumab biosimilars.
Phase 3 comparative biosimilar clinical studies have design features distinct from those for novel biological products.
Even if the RP is approved for multiple indications, pivotal phase 3 studies are done to demonstrate comparative efficacy and safety for biosimilars in one disease indication and extrapolated to other indications.
RP, reference product.

19. Faculty Commentary
To get a biosimilar approved, data from studies must show it is similar to the innovator biologic.
To alleviate uncertainty that the drugs would perform similarly, a single clinical trial is done with patients who have the condition that would be most sensitive for identifying differences between products.
In the future, this study can provide confidence that adalimumab biosimilars have similar actions as the innovator products; currently there are no adalimumab biosimilars on the market in the United States.