Exam 3: Lecture 14, Toxicology Drug Discovery and Development

Question 1

% New chemical entities that’s begin preclinical safety studies fail due to toxicity?

Answer 1

40%

Question 2

NCEs that enter clinical trials and fail?

Answer 2

89%

Question 3

highest costs of new drugs?

Answer 3

occurs in preclinical and clinical trials

Question 4

Biggest challenges facing Pharma industry today?

Answer 4

unanticipated adverse effects from promising new drug

late stage attrition increase time req to bring new drug to market, increase costs, major source of inefficiency

Question 5

drug development =

Answer 5

focused on eval of safety and efficacy of candidate drug in humans

Question 6

drug discovery =

Answer 6

screening new drug molecules in vitro and vivo

establish suitable models to test bio activities

set up working hypothesis

Question 7

major steps drug discovery process

Answer 7

“Early Discovery” = Hit -> Lead, 3-5 yrs

“Late-Discovery” = Lead -> optimization, 3-5 yrs

Question 8

Ultimate goal of toxicology studies?

Answer 8

translate animal model responses into understanding the risk of human subjects

Question 9

Typical toxicology profile consists of…

Answer 9

acute/subchronic/chronic toxicology
safety pharmacology
genetic toxicology
reproductive and developmental toxicology
eval of carcinogenic potential

Question 10

Limitations of preclinical safety testing?

Answer 10

toxicity testing time consuming/expensive

large numbers of animals may be needed to obtain valid preclinical data

extrapolations of TI and toxicity data from animals to humans are reasonably predictive for many but not all toxicities

for statistical reasons, rare adverse effects unlikely to be detected in preclinical trials

Question 11

IND includes

Answer 11

1. info on composition and source of drug
2. chemical and manufacturing info
3. all data from animal studies
4. proposed plan for clinical trials
5. names/credentials of physicians who conduct trials
6. compilation of key data relevant to study of drug in humans

Question 12

example of where toxicity in animals is unique and not relevant to humans?

Answer 12

phenobarbital

drugs that show classical phenobarbital-like effects and produce tumors in rodents can still be FDA aproved

Question 13

Personnel required for clinical trial?

Answer 13

basic scientist
clinical pharmacologists
clinician specialist
statisticians
and others

Question 14

Confounding factors in clinical trials?

Answer 14

variable natural history of most diseases

presence of other diseases and risk factors

placebo response

single-blind, double blind design

Question 15

Which 2 groups increasing # of FDA approvals?

Answer 15

antibody-based

oligonucleotide-based therapeutics

Question 16

Small molecules and oligonucleotides are approved under…

Answer 16

New molecular entities

Question 17

Protein-based candidates are approved under….

Answer 17

biologics license applications

Question 18

Immune checkpoint inhibitors work by

Answer 18

blocking PD-L1/PD-1 and allows T cell to kill tumor cell

Question 19

how Car-T therapy works

Answer 19

T cell and CAR are put together

CAR-T cell helps find and fight specific cells

Question 20

Leukapheresis or apheresis is..

Answer 20

CAR-T cell procedure