1. Biologics
Res Eman Zayed
Supervised by Prof Dr Ayman Madny

2. • Introduction
• Classification
• Commonly used agents and their pharmacology

3. • Abiological agent also called bio-agent, biological threat agent,
biological warfare agent, biological weapon, or bioweapon is a
bacterium, virus, protozoan, parasite, or fungus that can be used
purposefully as a weapon in bioterrorism or biological warfare
(BW)
• Biological Therapeutic Agents are drugs that are genetically
engineered from a living organism, such as a virus, gene or
protein, to simulate the body’s natural response to infection and
disease
• Common biological agents used are
 Tumor necrosis factor (TNF) inhibitors
 B-cells inhibitors
 Interleukin (IL) inhibitors
 Selective co-stimulation modulators

4. • A biopharmaceutical, also known as a biologic (al) medical
product, biological,or biologic, is any pharmaceutical drug
product manufactured in, extracted from, or semisynthesized
from biological sources
• Different from totally synthesized pharmaceuticals, they include
vaccines, blood, blood components, allergenics, somatic cells,
gene therapies, tissues, recombinant therapeutic protein, and
living cells used in cell therapy
• Biologics can be composed of sugars, proteins, or nucleic acids
or complex combinations of these substances, or may be living
cells or tissues.
• They (or their precursors or components) are isolated from
living sources—human, animal, plant, fungal, or microbial

5. Major classes
1. Extracted from living systems
Some of the oldest forms of biologics are extracted from the
bodies of animals, and other humans especially.
Important biologics include:
• Whole blood and other blood components
• Organs and tissue transplants
• Stem cell therapy

6. • Antibodies for passive immunization (e.g., to treat a virus
infection)
• Human breast milk
• Fecal microbiota
• Human reproductive cells
• Some biologics that were previously extracted from animals,
such as insulin, are now more commonly produced by
recombinant DNA

7. 2. Produced by recombinant DNA
• Blood factors (Factor VIII and Factor IX)
• Thrombolytic agents (tissue plasminogen activator)
• Hormones (insulin, glucagon, growth hormone,
gonadotrophins)
• Haematopoietic growth factors (Erythropoietin, colony
stimulating factors)

8. • Interferons (Interferons-α, -β, -γ)
• Interleukin-based products (Interleukin-2)
• Vaccines (Hepatitis B surface antigen)
• Monoclonal antibodies (Various)
• Additional products (tumour necrosis factor, therapeutic
enzymes)

9. 3. Vaccines
4. Gene therapy

10. • Strictly defined, a biologic is a treatment derived from an
organic source
• In this sense, vaccines for smallpox and rabies and antitoxins
for diphtheria and tetanus, which were introduced in the 19th
century, were among the first biologics
• Biologics that are derived from microorganisms, plant cells, or
animal cells are very large molecules that are often produced
by DNAtechnology (eg, monoclonal antibodies)
• Small molecules are chemically synthesized drugs that act
intracellularly (eg, sorafenib and bortezomib)

11. The 'Mabs'
• Monoclonal antibody names have four segments (and
usually five syllables)
• The first segment is the decision of the drug developer
• The next segment is the target or disease class, to which a
vowel may be added to allow pronunciation
• The third segment of the name indicates the source (eg,
human, mouse) and is useful for predicting immunogenicity
• The last syllable is "mab," for "monoclonal antibody

15. The 'Mibs'
• The suffix "zomib" is the designation for protease or
proteasome inhibitors
• Mibs are small molecules that work inside cancer cells to slow
proliferation and increase apoptosis (cell death)

16. The 'Nibs'
• The suffix "nib" indicates a small-molecule inhibitor ("nib" is
verbal shorthand for "inhibit") of kinase enzymes
• More specifically, "tinib" is used for tyrosine kinase inhibitors,
"anib" for angiogenesis inhibitors, and rafenib for rapidly
accelerated fibrosarcoma (RAF) kinase inhibitors

18. Anti-TNF Agents
• Infliximab (chimeric monoclonal antibody)
• Adalimumab and Golimumab (Humanized monoclonal antibody)
• Certolizumab pegol (Pegylated Fc-free fragment of a humanized
monoclonal antibody with binding specificity for TNF-α
• Etanercept is a soluble fusion protein comprising the TNF receptor
2 in covalent linkage with the Fc portion of IgG1.

19. • Uses of infliximab: Rheumatoid arthritis, Ankylosing
spondylitis, Inflammatory bowel diseases, Psoriasis, Idiopathic
pulmonary fibrosis and Sarcoidosis
• Uses of adalimumab: Hidradenitis Suppurativa, Uveitis,
Behcet's Disease and above
• Uses of certolozimumab: Moderate-to-Severe Crohn Disease,
Moderate-to-Severe Rheumatoid Arthritis, Active Psoriatic
Arthritis andActiveAnkylosing Spondylitis
• Uses of Golimumab: RheumatoidArthritis, PsoriaticArthritis,
Ankylosing Spondylitis and Ulcerative Colitis
• Uses of Etanercept:Ankylosing Spondylitis,Adult
RheumatoidArthritis, PsoriaticArthritis and Plaque Psoriasis

20. ADR
• Avoided in patients with active infection or a history of
hypersensitivity
• Increased risk for infection, especially opportunistic
fungal infection and reactivation of latent tuberculosis
• Lymphoma risk
• Drug-induced lupus
• Neurologic deficits

21. Dosage
• Etanercept: 50 mg SQ weekly, or 25 mg SQ biweekly
• Adalimumab: 40 mg SQ every other week
• Golimumab: 50 mg SQ monthly
• Certolizumab: 400 mg SQ weeks 0, 2, 4 then 200 mg
every other week

22. Abatacept
• Fusion protein consisting of the extracellular domain of human
cytotoxic T lymphocyte–associated antigen 4 (CTLA-4) linked
to the modified portion of human IgG
• It inhibits the co-stimulation of T cells by blocking CD28-
CD80/86 interactions and may also inhibit the function of
antigen-presenting cells by reverse signaling through CD80
and CD86
• Onset of action is usually slower than that of the anti-TNF
agents

23. • Dose: Weight based
 <60 kg: 500 mg
 60–100 kg: 750 mg
 >100 kg: 1000 mg
 IV dose at week 0, 2 and 4, and then every 4 weeks
• Uses:
 RheumatoidArthritis
 Diabetes Mellitus Type 1

24. ADR
• Risk of bacterial and viral infections
• Headache
• Nausea

25. Anakinra
• Recombinant form of the naturally occurring IL-1 receptor
antagonist
• Uses
 RheumatoidArthritis
 Neonatal-onset inflammatory disease,
 Muckle-Wells syndrome,
 Familial cold urticaria, Systemic juvenile-onset inflammatory
arthritis,
 Adult-onset Still's disease

26. • Dose: 100 mg SQ daily
• ADR
 Risk of bacterial, viral infections
 Reactivation of latent TB
 Neutropenia
 Injection site reaction
 Headache

27. Anti integrins
Natalizumab:
• Activity againstAlpha4 (4) integrin along with its beta1
or beta7 subunit
• Uses: Multiple Sclerosis, Crohn’s Disease
• Dose: 300 mg IV infusion over 1hr q4Weeks
• Risk of PML, Hepatic toxicity and increase risk of
infection

28. V
edolizumab:Activity againstAlpha4 (4) integrin beta7 subunit
• Use: Inflammatory bowel disease
• Dose
 Induction: 300 mg IV at weeks 0, 2, and 6, THEN
 Maintenance: 300 mg IV q8weeks
ADR: Increase risk of infection and hepatic toxicity

29. Rituximab
• Chimeric monoclonal antibody directed against CD20, a cell-surface
molecule expressed by most mature B-lymphocytes
• Dose: 1000 mg IV x 2, day 0 and 14; May repeat course every 24
weeks or more
• ADR
 Risk of bacterial, viral infections
 Infusion reaction
 Rash
 Fever
 PML
 Cytopenia
 Hepatitis B reactivation

30. • Uses
 Non-Hodgkin Lymphoma
 SLE
 Chronic Lymphocytic Leukemia
 RheumatoidArthritis
 Wegener Granulomatosis
 Microscopic Polyangiitis
 Immune thrombocytopenic purpura (ITP), Pemphigus vulgaris,
Rasmussen Encephalitis

31. Belimumab
• Directed against the ligand of the BLyS/BAFF receptor on B
cells that promotes B cell survival and differentiation to
plasmablasts
• Use: SLE
• Dose: 10 mg/kg i.v., wk 0,2,4 then monthly
• ADR: Infusion reactions,Allergy, Infections

32. Alemtuzumab
• Directed against CD52 antigen, which is exxpressed on both
monocytes and lymphocytes
• Causes lymphocyte depletion of both B and T cells
• Uses: Chronic Lymphocytic Leukemia, Multiple Sclerosis and
Kidney Transplantation

33. • Dose for MS:
 First treatment course: 12 mg/day IV on 5 consecutive days
(60 mg total dose)
 Second treatment course: 12 mg/day on 3 consecutive days (36
mg total dose) given 12 months after the first treatment course
• ADR:
1. Autoimmune diseases like thyroiditis, Grave’s disease,
thrombocytopenia, hemolytic anemia, pancytopenia,
antiglomerular basement membrane disease and membranous
glomerulonephritis

34. 2.Malignancies such as thyroid cancer, melanoma, breast cancer,
HPV related cancer
3. Serious infections
4. Infusion reactions

35. Tocilizumab
• Humanized monoclonal antibody directed against the membrane
and soluble forms of the IL-6 receptor
• Dose: 4–8 mg/kg; 8 mg/kg IV monthly
• Uses: RheumatoidArthritis, Systemic Sclerosis
• ADR
 Risk of infection
 Infusion reaction
 LFT elevation
 Dyslipidemia
 Cytopenias

36. Tofacitinib
• Inhibitor of JAK 1 and JAK 3 which mediate signalling of
receptors for common gamma chain related cytokines such as
IL-2, 4, 6, 7, 9, 15, 21 and gamma interferon alpha
• Uses: RheumatoidArthritis, IBD
• Dose: 5mg orally BD
• ADR: Risk of infection, LFT and creatinine elevation,
dyslipidemia and neutropenia
• Other less commonADR: URTI, Diarrhea, headache,
nasopharyngitis

37. Antibodies against agents
ATI/ HACA (Humanised antichimeric antibody):
• More common with infliximab than with adalimumab or
certololizumab pegol
• Develops in 13% of patients treated with infliximab
• Likely to develop infusion reactions consisting of chest
tightness, dyspnea, rash and hypotension
• Less likely to develop in patients treated with glucocorticoids
or immune modulators

38. • Delayed hypersensitivity reactions, consisting of severe
polyarthralgia, mylgia, facial edema, urticaria or rash which are
unusual complications occuring after 2 to 12 days after infusion
• HighATI appear in such patients after occurrence of such
reactions
• Risk factor appear to be a long delay between infusions ( ≥6
months)
• Less common if standard induction regimen or immune
modulator concurrently
• Lower infliximab serum levels in the setting of episodic therapy
whereATI is highest

39. HAHA( Human anti human antibodies):
• 2.6 % of patients in a 1 year maintenance of adalimumab in
Crohn’s disease 17% in patients with RA
• Antibody to certolozimumab develop in about 10% in
induction and maintenance trials
• Decreased response to adalimumab

40. ANA/ dsDNA:
• 50% of patients receiving infliximab after 2 years
• Out of which 30% develop ds DNA
• More common with infliximab or adalimumab than
certolizumab
• Clinical significance unknown