Increasing knowledge of genetics and cell processes leads to potential new biologic (and drug) targets at each step in the protein-production process. This leads to new therapies, which in turn lead to new understanding of diseases. Here is an update on relatively new drugs called biologics...

1. Dr. Ananya Chakraborty, MD
Professor, Pharmacology, VIMS & RC
Member, Board of studies, RGUHS
Ethics Committee Member, Manipal Hospital
Secretary, IPS-B- Bangalore Chapter
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3. the “Poison of Kings” and the
“Saviour of…………”
Compound “606”…
What is it?
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4. Introduction
The journey of biologics
 The expectations
 The challenges
Biosimilars
 The regulations
 The road ahead
Biological drugs in dermatology
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5. Protein-based drug from living cells
 Human, animal, microorganisms
 PREVENTION, TREATMENT or CURE of disease
Examples of biological products
 Vaccines
 Blood products for transfusion
 Allergenic extracts
 Gene therapies, Analogous products
http://www.fda.gov/AboutFDA/Transparency/Basics/ucm194516.htm
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6. Monoclonal antibodies
Fusion antibody proteins
Recombinant human cytokines and
growth factors
Sehgal VN, Pandhi D and Khurana A. Biologics in dermatology: An Integrated Review. Ind J Dermat 2014;59(5): 425-441.
Hassan I, Aleem S, Sheikh G and Anwar P. Biologics in dermatology: A Brief Review. British J Medical Practitioner 2013;6(4).
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7. http://www.nobleprize.org
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10.  Large molecules, specific to targets
 Contain IgG Fc pieces as part of construct
 Actions on the immune system
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11. Biosynthetic "human" insulin
Marketed: Since 1982
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12.  Chimeric proteins
 Created by fusion of the receptor domain of a
human protein with the constant region of IgG
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13. Improved tolerability
Convenience in usage
Lasting remissions
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14. The manufacturing processes:
Complex and very sensitive
Slight changes in temperature or
other factors: Impact the final product
Changes in the manufacturing process
or facility: Clinical studies to
demonstrate safety, purity and potency
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Copies of biologic drugs
developed after the
patent of an original
expired
Similar to the reference
product, but are virtually
never the same

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Monoclonal antibodies
•Infliximab (1998, Anti-TNFalpha)
•Adalimumab (Anti-TNFalpha human)
•Rituximab (Anti CD20)
•Basiliximab (Anti CD25)
•Omalizumab (Anti IgE)
•Itolizumab (2013 Biocon; Anti CD6)
• Remicade (Pfizer 2016,
biosimilar of Infliximab)
• Exemptia (Zydus cadila 2014,
biosimilar of Adalimumab)
•Reditux (Dr Reddy’s 1997,
world’s first biosimilar of
Rituximab)
Fusion anibody proteins
•Eternacept (1998)
• Alefacept
Benepali (Biogen 2016,
biosimilar of Eternacept)
Recombinant human cytokines and
growth factors
Interferon alpha, Anakinra (IL1Ra),
GM-CSF, PDGF
Drugs in the pipeline

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19.  Drug development:
 Three levels of fermentation
 Upstream process Pka data
 Reference not marketed in India
 Reference biologic lisensed in any ICH country
 EU, Japan, US, Canada and Switzerland
 Post marketing study:
 Within 2 yrs of marketing permission
 More than 200 evaluable patients
 Primary endpoint as “SAFETY”
Raps.org/Regulatory-Focus/Nres/2016/03/28/24638/India-Releases-New-Biosimilars-Guidance/
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20. Infliximab
 Psoriasis: Psoriatic arthritis and plaque
psoriasis
 Atopic dermatitis, Hidradenitis suppurativa
 Dose: 5 or 10mg/kg i.v. infusion over a period
of 2 hours at weeks 0, 2 and 6, followed up
with a repeat single infusion at 8-12 weeks
Adalimumab
 Administered subcutaneously
 Dose: 80mg  40mg every other week
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21. Pyoderma gangrenosum
 Case reports with Adalimumab
 Case reports with Eternacept
Autoimmune bullous disease
 Efficacy studies with Infliximab
 Case report with Eternacept  tapering of steroid
Connective tissue disorders
 Retrospective study with Eternacept
 ? Infliximab
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22. Rituximab
 Pemphigus vulgaris
 Paraneoplastic pempgigus
 Cutaneous B-cell lymphoma
Intravenous immunoglobulin
 Autoimmune bullous disorders
 Connective tissue diseases
 Kaposi’s sarcoma
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23. Increased incidence of infections
Reactivation of tuberculosis
Relapse during treatment or
inadequate response
Usage in special population
 Pediatrics, Geriatrics
 Pregnancy and lactation
Carcinogenic potential?
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25.  In-depth understanding of the real-life
capabilities, in terms of both efficacy and
safety of biologics is emerging
 Drug selection based on multiple factors
 Patient preference, cost, tolerance
 Adverse effects, dosing schedule
 Mode of administration
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