Biologics

Question 1

what are the types of biologics?

Answer 1

1. monoclonal antibodies (mAbs)
2. proteins/peptides
   e.g. growth factors
3. RNA-based therapeutics
   e.g. microRNAs

Question 2

how can RNAi be used in biologics?

Answer 2

they are antisense RNA (microRNA) molecules that target mRNAs for degradation to control disease states

Question 3

what are the stages of antibody drug pipeline? and what do they contain?

Answer 3

Question 4

whats the difference between small molecule drugs and biologics?

Answer 4

Question 5

whats the difference between small molecule drugs and mABs?

Answer 5

Question 6

how can small molecule drugs and antibodies differ in targeting HER2 receptors in breast cancer?

Answer 6

Question 7

what are bi-specifics? and when do you use them?

Answer 7

use them when you want to target two different proteins or two sites on the same protein (bi-paratopic)

this increases the efficacy of inhibition of protein activity

Question 8

what are antibody drug conjugates (ADCs)?

Answer 8

antibody target specific antigen
drug is linked to the antibody and is delivered to the targeted cell using a linker

Question 9

how can you increase tissue penetration of ADCs?

Answer 9

using Fabs and scFvs to improve penetration as the Fc domain is not required

Question 10

what are Antibody-oligonucleotide Conjuagtes?

Answer 10

Antisense Oligoncleotide allow silencing of intracellular drug targets
However, specific delivery across the plasma membrane is a challenge

Question 11

what are the PK considerations of biologics?

Answer 11

1.oral bioavailability is low due to enzymatic digestion in the GI tract therefore most are given through IV/subcut/intramuscular
2. slow absorption due to their size = longer to reach peak conc.
3. poor distribution
4. eliminated via intracellular lysosomal proteolytic degradation
5. drug interactions

Question 12

what are the main interactions of biologics?

Answer 12

Exposure to factors in the blood e.g platelets
Binding to neonatal Fc Receptors (FcRn) allowing recycling
Immunogenicity e.g production of anti-drug antibodies (ADA) and neutralising antibodies
Interactions with other drugs (polypharmacy)

Question 13

what drugs impact Fc receptors/domains ?

Answer 13

romiplostim

Question 14

what is romiplostim?

Answer 14

Thrombopoietin mimetic for patients with ITP (Immune thrombocytopenia)
»Binds to Thrombopoeitin receptor and promotes platelet production
Fusion protein analog of thrombopoietin, a hormone that regulates platelet production
Binding of the drug to platelets affects its clearance
MONITORING REQUIRED

Question 15

what is immunogenicity to biologics?

Answer 15

1. Production of anti-drug antibodies (ADA)
   »Potential adverse events
2. Production of neutralising antibodies (NAb)
   »Decrease in efficacy over time and potential treatment failure

Question 16

importance of influximab treatment?

Answer 16

Infliximab is a mAb prescribed for patients with RA, Crohn’s, Psoriasis
- Binds to TNFa and prevents TNFa binding to the TNF receptor of target cells

Question 17

what occurs between tocilzumab and simvastatin? how can this be avoided?

Answer 17

1. drug-drug interaction

pt with RA, sjrogrens = have elevated pro inflammatory cytokines = reducing CYP activity
= reduce drug metabolism = increases simvastatin exposure time