Acceptable changes in quality attributes of glycosylated biopharmaceuticals Schiestl M, Stangler T, Torella C, et al. Nat Biotechnol. 2011;29(4):310-2. http://www.nature.com/nbt/journal/v29/n4/full/nbt.1839.html

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

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.

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.

[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] http://www.tandfonline.com/doi/full/10.1080/03007995.2017.1288612

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.

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.

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. http://ard.bmj.com/content/76/2/355.long

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.

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.

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.

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. http://journals.lww.com/ibdjournal/Abstract/2017/02000/The_PROSIT_BIO_Cohort___A_Prospective.7.aspx

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 4.3 +/- 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

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.

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.

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):e000154. http://rmdopen.bmj.com/content/2/1/e000154

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.

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.