Drug Development Essay

7/27/2019 Drug Development Essay

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How are biotechnology medicines discovered and developed? (AMGEN)

The first step in treating any disease is to clarify how the disease is caused. Many questions must

be answered to arrive at an understanding of what is needed to pursue new types of treatments.

How does a person get the disease? Which cells are affected? Is the disease caused by genetic factors? If so, what genes are turned on or off in the

diseased cells?

What proteins are present or absent in diseased cells as compared with healthy cells? If the disease is caused by an infection, how does the infectious organism interact with

the body?

In modern labs, sophisticated tools are used for shedding light on these questions. The tools are

designed to uncover the molecular roots of disease and pinpoint critical differences between

healthy cells and diseased cells. Researchers often use multiple approaches to create a detailed

picture of the disease process. Once the picture starts to emerge, it can still take years to learn

which of the changes linked to a disease are most important. Is the change the result of the

disease, or is the disease the result of the change? By determining which molecular defects are

really behind a disease, scientists can identify the best targets for new medicines. In some cases,the best target for the disease may already be addressed by an existing medicine, and the aim

would be to develop a new drug that offers other advantages. Often, though, drug discovery aims

to provide an entirely new type of therapy by pursuing a novel target.

Selecting a target

The term targetrefers to the specific molecule in the body that a medicine is designed to affect.

For example, antibiotics target specific proteins that are not found in humans but are critical to

the survival of bacteria. Many cholesterol drugs target enzymes that the body uses to make

cholesterol.

Scientists estimate there are about 8,000 therapeutic targets that might provide a basis for new


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medicines. Most are proteins of various types, including enzymes, growth factors, cell receptors,

and cell-signaling molecules. Some targets are present in excess during disease, so the goal is to

block their activity. This can be done by a medicine that binds to the target to prevent it from

interacting with other molecules in the body. In other cases, the target protein is deficient or

missing, and the goal is to enhance or replace it in order to restore healthy function.

Biotechnology has made it possible to create therapies that are similar or identical to the complex

molecules the body relies on to remain healthy.

The amazing complexity of human biology makes it a challenge to choose good targets. It can

take many years of research and clinical trials to learn that a new target wont provide the desired

results. To reduce that risk, scientists try to prove the value of targets through research

experiments that show the targets role in the disease process. The goal is to show that the

activity of the target is driving the course of the disease.

Selecting a drug

Once the target has been set, the next step is to identify a drug that impacts the target in the

desired way. If researchers decide to use a chemical compound, a technology called drug

screening is typically used. With automated systems, scientists can rapidly test thousands of

compounds to see which ones interfere with the targets activity. Potent compounds can be put

through added tests to find a lead compound with the best potential to become a drug.

In contrast, biologics are designed using genetic engineering. If the goal is to provide a missing

or deficient protein, the gene for that protein is used for making a recombinant version of the

protein to give to patients. If the goal is to block the target protein with an antibody, one common

approach is to expose transgenic mice to the target so as to induce their immune systems to make

antibodies to that protein. The cells that produce these specific antibodies are then extracted and

manipulated to create a new cell line. The mice used in this process are genetically modified to

make human antibodies, which reduces the risk of allergic reactions in patients.

Developing the drug

Once a promising test drug has been identified, it must go through extensive testing before it can

be studied in humans. Many drug safety studies are performed using cell lines engineered to


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express the genes that are often responsible for side effects. Cell line models have decreased the

number of animals needed for testing and have helped accelerate the drug development process.

Some animal tests are still required to ensure that the drug doesnt interfere with the complex

biological functions that are found only in higher life-forms.

If a test drug has no serious safety issues in preclinical studies, researchers can ask for regulatory

permission to do clinical trials in humans. There are three phases of clinical research, and a drug

must meet success criteria at each phase before moving on to the next one.

Phase 1: Tests in 20 to 80 healthy volunteers and, sometimes, patients. The main goals are to

assess safety and tolerability and explore how the drug behaves in the body (how long it stays in

the body, how much of the drug reaches its target, etc.).

Phase 2: Studies in about 100 to 300 patients. The goals are to evaluate whether the drug appears

effective, to further explore its safety, and to determine the best dose.


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Phase 3: Large studies involving 500 to 5,000 or more patients, depending on the disease and the

study design. Very large trials are often needed to determine whether a drug can prevent bad

health outcomes. The goal is to compare the effectiveness, safety, and tolerability of the test drug

with another drug or a placebo.

If the test drug shows clear benefits and acceptable risks in phase 3, the company can file an

application requesting regulatory approval to market the drug. In the United States, the Food and

Drug Administration evaluates new medicines. In the European Union, the European Medicines

Agency manages that responsibility. Regulators review data from all studies and decide whether

the medicines benefits outweigh any risks it may have. If the medicine is approved, regulators

may still require a plan to reduce any risk to patients. A plan to monitor side effects in patients is

also required.

A company can continue doing clinical trials on an approved medicine to see if it works under

other specific conditions or in other groups of patients, and additional trials may also be required

by regulatory agencies. These are known as phase 4 studies.

The whole drug development process takes 10 to 15 years to complete on average. Very few test

drugs are able to clear all the hurdles along the way.

Why is it better to fail early?

Fail early, fail cheap is the goal.No company wants to discover a major problem after millions

of dollars and years of research have been invested, once clinical trials are well under way as is

the case with Rezulin ( Anti diabetic and anti inflammatory drug) (Varma-OBrien, S., 2009).

Biotechnology companies have been attempting to decrease the technical uncertainty

surrounding a product before it enters the expensive stages of developmentin particular Phases

II and III, when there are significant costs associated with recruiting patients and monitoring

them for extended periods.


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Savings realised by avoiding late-stage R&D failures are re-invested in R&D to further enhance

R&D productivity through work on candidate selection, first efficacy dose, first human dose, and

product decision. Key to the quick win/fast fail approach is a feedback loop in which data

gathered at the early proof of concept stage are fed back to discovery scientists for future benefit.

Drug developers can remove some of the uncertainty in the outcomes of their research and

improve their return on investment substantially. For example, demonstrating in the course of a

year that a drug forAlzheimers does or does not alter the disease progression before it becomes

symptomatic would produce savings over having to wait perhaps five years for the conclusion of

a later-phase study.

What is the rationale for the high costs of medicines developed by Pharma?

Research and development costs vary widely from one new drug to the next. Those costs depend

on the type of drug being developed, the likelihood of failure, and whether the drug is based on a

molecule not used before in any pharmaceutical product (a new molecular entity, or NME) or

instead is an incremental modification of an existing drug. A recent, widely circulated estimate

put the average cost of developing an innovative new drug at more than $800 million, including

expenditures on failed projects and the value of forgone alternative investments (Marron D.B,

The Congress of the United States, 2006).

Clinical research is expensive. This is demonstrated by Phase I and II protocols. They experience

the biggest annual growth in complexity and execution as more data is gathered in these earlier

phases. Similarly, Phase IV is expensive as more post-marketing data is collected for safety and

marketing purposes. But the main expense is failure. AstraZeneca does badly by this measure

because it has had so few new drugs hit the market.

Drug Development Essay

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