Benefits and Risks to Biosimilars :

from a Patient Perspective?

• Dr Tanoy Bose. MD. EULAR Cert.Rheumatology

Consultant
Department of Rheumatology & Internal Medicine
Narayana Health Rabindranath Tagore Surgical Center
Hiland Park, Kolkata, West Bengal
Biosimilar: Definition

Highly similar to the reference

product not with- standing minor
differences in clinically inactive
components,” and that “there are no
clinically meaningful differences
between the biologic product and the
reference product in terms of the
safety, purity, and potency of the
product.

1. Biologics Price Competition and Innovation Act of 2009, United States Code. Pub- lic Law 111–148, 124 Stat. 119, x7001-7003.
 Biosimilar & Biologics: Differences

Parameters Biologics Biosimilars

Neucleotide Sequence of Starting

Original Different
Gene

Codons 20 18

Translated Amino Acid Sequence Similar Similar

Vector Used Proprietary May be same or different

Post Translational Modification

(Choice of Cell Line)
Proprietary May be same or different

Culture Medium for Cell Line

Proprietary May be same or different
growth

Bioreactors Proprietary Similar but not identical

Process of harvesting from cell culture

(Filtration, Centrifugation etc)
Proprietary Different

Therapeutic Benefit Reference Similar

Cost Reference Cheaper

 Biosimilar: Approval criteria

• Must demonstrate similar efficacy and safety, compared with its reference product,
• In a pharmacokinetic study that typically is conducted in healthy volunteers, and
• In at least 1 randomized, double-blind, parallel group, active comparator clinical trial
conducted in patients with that disease indication which is most sensitive to detect potential
differences between the biosimilar candidate and its reference product.

• If an appropriate biomarker is available to assess response to therapy, a pharmacodynamic study

may be performed in patients with a disease for which the reference product is indicated.

• However, no such biomarker is yet available that adequately reflects response to treatment in
rheumatologic diseases. In these clinical studies, the biosimilar candidate must also demonstrate
comparable safety and immunogenicity with its reference product.

1. US Food & Drug Administration. Guidance for industry. Scientific considerations in demonstrating biosimilarity to a reference product. 2015.
Biosimilar: Advantages in approval
• All aspects of the biosimilar development program are considered together and are given equal
weight. Once equivalent efficacy and comparable safety of the biosimilar and its reference
product have been demonstrated, an approved biosimilar can be considered like another
batch of its reference product.

• Because efficacy and safety of the reference product already have been demonstrated in each
indication for which it has been approved, efficacy of the biosimilar need not be
demonstrated in every indication.

• Accumulated clinical experience with the reference product in all indications for which it is
approved can be extrapolated to the biosimilar. This opportunity for “extrapolation of
indications” in the abbreviated biosimilar approval pathway markedly reduces development
costs by eliminating the need to conduct expensive clinical trials of the biosimilar candidate in
each indication for which approval is sought.

• A biosimilar may have fewer associated adverse effects and be less immunogenic than its
reference product, provided that pharmacokinetic parameters and efficacy are equivalent.
 Biosimilar: Patient’s Perspective

• Its a WIN WIN situation for the

patients …psst if oversimplified
Only prospective, double-blind, randomized controlled trial that has
compared transitioning from a reference product with its biosimilar to
continued treatment with the reference product
 spondyloarthritis(19%), rheumatoid arthritis(16%), psoriatic arthritis(6%), and chronic

NOR-SWITCH
plaque psoriasis(7%). Trial: Summary
• 482 patients with stable disease activity for 6 months. Randomised 1:1 with Originator
and Biosimilar (allowed to switch with maintained dosing regime)

• Period of study 52 weeks

• Primary end point: Worsening of Disease activity
• Results:
• Disease worsening occurred in 53 (26%) patients in the infliximab originator group and
61 (30%) patients in the CT-P13 group (per-protocol set; adjusted treatment difference

−4·4%, 95% CI −12·7 to 3·9). The frequency of adverse events was similar between

groups (for serious adverse events, 24 [10%] for infliximab originator vs 21 [9%] for

CT-P13; for overall adverse events, 168 [70%] vs 164 [68%]; and for adverse events

leading to discontinuation, nine [4%] vs eight [3%], respectively)

• Conclusion:
• Changing to the biosimilar was noninferior to continuing treatment with the
reference product over 52 weeks in the combined population of patients with the 6

inflammatory diseases. Trough drug concentrations throughout the study and the
• 802 patients of RA,PsA, AS. All switched from INFX(originator) to Biosimilar as per government
guidelines (to save cost of therapy)

• INX treatment duration 4.3-9.5yrs(Mean 6.5 yrs)

• Evaluated for disease activity and retention rate for next 12 months.

• One year Retention rate was less for RA, Previous INX use <5yrs and No DAS 28 remission

• Disease activity remain grossly unchanged through out the observation period.
Biosimilar: The NOCEBO effect

When a patient with stable disease activity that

has been controlled on treatment with a
reference product is changed to its biosimilar,
he or she may anticipate decreased efficacy and
lesser safety of the biosimilar and therefore
may experience subjective disease worsening
or adverse events on the new medication
• 196 pts out of 222 gave consent to shift (open label transition) the treatment from REM to CT-
P13(Biosimilar) for RA, AS and PsA.

• One fourth of the patients discontinued CT-P13 after the open-label transition, which was mainly
driven by an increase in the subjective tender joint count and the patient’s global assessment of
disease activity and/or in subjective AEs, rather than by an increase in objective signs and symptoms.

• Two recent surveys investigating patient perspectives on biosimilar drugs in diabetes and inflammatory bowel
disease showed that the majority of respondents had doubts and concerns about the effectiveness and safety of the
biosimilar drugs
• Some respondents equated lower costs with diminished quality.
• Respondents had more trust in prescription of biosimilar drugs by their treating physician than by regulatory
agencies, highlighting the importance of a good doctor–patient relationship.
Overcoming the NOCEBO Effect
Final Comments: Summary

• Nocebo effect

• Quality Control

• Competitive Pricing and Government intervention

• Unpredictable Immunogenicity

• Patient orientation
Final Comments: Summary

• The justification for biosimilars is that the potential risk to an individual patient of switching to
a lower-cost biosimilar should be outweighed by the potential benefit to society of expanding
access to care for all.

• Given that a biosimilar should have equivalent efficacy and comparable safety with its reference
product, the advantage of a biosimilar should be lower cost

• Even if the actual cost of a biosimilar is higher than that of its reference product, the
introduction of the biosimilar likely provoked reduction of the reference product’s price
Thank you