DDD LEC - DRUG DISCOVERY & DEVELOPMENT PROCESS

Drug Discovery

It includes all of the experimentation and studies designed to move a program from the initial identification of a biological target and associated disease state to the identification of a single compound with the potential to be clinically relevant.

Drug Development

Typically begins once a single compound has been identified, which is then progressed through various studies designed to support its approval for sale by the appropriate regulatory bodies

Target Discovery

Phase 1 is known as

Lead Discovery

Phase 2 is known as

Lead Optimization

Phase 3 is known as

Phase 1: Target Discovery

This process, often referred to as target progression and target validation, is accomplished through the use of molecular probes designed to identify multiple series of compounds that will modulate the activity of the biological target of interest.

Phase 2: Lead Discovery

It sets of structurally related compounds with the desired biological activity are identified through biological screening of large numbers of compounds.

Phase 3: Lead Optimization

In this phase, structural analogs within a lead series are studied to identify a single compound that may be progressed into the drug development stage.

Submission of Investigational New Drug (IND) Application

1st Step in Drug Development

Investigational New Drug (IND) Application

• Permit a clinical compound to move into human study

• This document provides regulatory agencies with detailed preclinical data describing animal pharmacology and toxicology studies, chemical manufacturing information and, detailed clinical protocols that describe how the clinical compounds will be studied in human populations if the studies are approved.

20 – 100

Clinical trial Phase 1 participants

100 – 300

Clinical trial Phase 2 participants

300-1000

Clinical trial Phase 3 participants

Safety and Tolerability

Clinical trial Phase 1 Goal

Safety and Effectiveness

Clinical trial Phase 2 and 3 Goal

Detect rare adverse effects across a much larger population

Clinical trial Phase 4 (Post Marketing Surveillance) Goal

Phase 1

What Clinical Trial Phase?
Phase intending to determine if safety margins are suitable for further progression in the clinical trial process.

Phase 1

What Clinical Trial Phase?
Pharmacokinetic and pharmacodynamic aspects of the candidate are closely monitored, and the drug candidate is typically administered first in a single ascending dose (SAD) study, followed by a multiple ascending dose (MAD) study

Phase 1

What Clinical Trial Phase?

The data developed through the course of this phase’s studies are used to determine the dose that will be used in phase II and phase III clinical trials

Phase 2

What Clinical Trial Phase?

is designed to determine whether or not the clinical candidate provides the desired biological impact. Safety studies also continue through this trial phase

Phase 2A

What Clinical Trial Phase 2?
The goal is to determine the dose required to provide the desired therapeutic impact or endpoint for the clinical candidate. Once the proper dose levels are determined

Phase 2B

What Clinical Trial Phase 2?

The goal of this phase’s studies is to determine the overall efficacy of candidate compounds in a limited population of subjects.

Phase 3

What Clinical Trial Phase?

studies are typically randomized and involve hundreds to thousands of patients at multiple clinical trial sites and are designed to determine the efficacy of the candidate compound relative to the current standard of care.

Phase 3

What Clinical Trial Phase?

Patients are also closely monitored for adverse side effects, as the larger patient pools can identify safety issues that did not become apparent in smaller phase II trials.

Phase 3

What Clinical Trial Phase?
Considered as the most expensive aspect of drug discovery and development, considering the number of subjects, time requirements, and complex design.

Submission of New Drug Application (NDA)

3rd Step in Drug Development

New Drug Application (NDA)

This document typically contains comprehensive details of both animal and human studies, all safety findings (adverse and side effects), manufacturing procedures (including methods of analysis to ensure drug quality), detailed formulation information for all dosing methods studied, and storage conditions.

Phase 4

What Clinical Trial Phase?

In general, these studies are designed to detect rare adverse effects across a much larger population of patients than could be supported in phase III trials or long-term adverse effects that might be outside of the scope of phase III trial durations.

Phase 4

What Clinical Trial Phase?

The impact of studies can include alterations to labeling based on safety results, contraindication for use of the new drug in combination with other medications, or even the withdrawal of marketing approval if the findings are severe enough.

Phase 4

What Clinical Trial Phase?

Safety studies are not the only reason for conducting clinical trials, data provided in this phase is often used it in post marketing surveillance and additional clinical studies to identify competitive advantages, new markets, and new indication for their products.

Rofecoxib (Vioxx)

Clinicial Trial Phase 4 example:
– a COX-2 selective NSAID was removed from the market after phase IV due to risk of ischemic events in patients.

Cerivastatin (Baycol)

Clinicial Trial Phase 4 example:

an HMG-CoA reductase inhibitor marketed by Bayer AF for the treatment of high cholesterol and cardiovascular disease was voluntarily removed from the market after reports of fatal rhabdomyolysis