National Institutes Of Health Announces New Program To Develop Therapeutics For

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National Institutes Of Health Announces New Program To Develop Therapeutics For

Rare And Neglected Diseases

http://www.medicalnewstoday.com/articles/151541.php

The National Institutes of Health is launching the first integrated, drug

development pipeline to produce new treatments for rare and neglected diseases.

The $24 million program jumpstarts a trans-NIH initiative called the

Therapeutics for Rare and Neglected Diseases program, or TRND.

The program is unusual because TRND creates a drug development pipeline within

the NIH and is specifically intended to stimulate research collaborations with

academic scientists working on rare illnesses. The NIH Office of Rare Diseases

Research (ORDR) will oversee the program, and TRND's laboratory operations will

be administered by the National Human Genome Research Institute (NHGRI), which

also operates the NIH Chemical Genomics Center (NCGC), a principal collaborator

in TRND. Other NIH components will also participate in the initiative.

A rare disease is one that affects fewer than 200,000 Americans. NIH estimates

that, in total, more than 6,800 rare diseases afflict more than 25 million

Americans. However, effective pharmacologic treatments exist for only about 200

of these illnesses. Many neglected diseases also lack treatments. Unlike rare

diseases, however, neglected diseases may be quite common in some parts of the

world, especially in developing countries where people cannot afford expensive

treatments. Private companies seldom pursue new therapies for these types of

illnesses because of high costs and failure rates and the low likelihood of

recovering investments or making a profit.

" NIH is eager to begin the work to find solutions for millions of our fellow

citizens faced with rare or neglected illnesses, " said NIH Acting Director

Raynard S. Kington, M.D., Ph.D. " The federal government may be the only

institution that can take the financial risks needed to jumpstart the

development of treatments for these diseases, and NIH clearly has the scientific

capability to do the work. "

Developing Drugs

The drug development process is complicated and expensive. Studies suggest that

it currently takes more than a dozen years and hundreds of millions of dollars

to take a potential drug from discovery to the marketplace. And the failure rate

is high.

" This initiative is really good news for patients with rare or neglected

diseases, " said ORDR Director C. Groft, Pharm.D. " While Congress has

previously taken important steps to help these patients, such as providing

incentives for drug companies under the Orphan Drug Act, this is the first time

NIH is providing support for specific, preclinical research and product

development known to be major barriers preventing potential therapies from

entering into clinical trials for rare or neglected disorders. While we do not

underestimate the difficulty of developing treatments for people with these

illnesses, this program provides new hope to many people world-wide. "

Typically, drug development begins when academic researchers studying the

underlying cause of a disease discover a new molecular target or a chemical that

may have a therapeutic effect. Too often, the process gets stuck at the point of

discovery because few academic researchers can conduct all the types of studies

needed to develop a new drug. If a pharmaceutical company with the resources to

further the research does get involved, substantial preclinical work begins with

efforts to optimize the chemistry of the potential drug. This involves an

iterative series of chemical modifications and tests in progressively more

complex systems - from cell cultures to animal tests - to refine the potential

medicine for use in people. Only if these stages are successful can a potential

treatment move to clinical trials in patients.

Unfortunately, the success rate in this preclinical process is low, with 80 to

90 percent of projects failing in the preclinical phase and never making it to

clinical trials. And the costs are high: it takes two to four years of work and

$10 million, on average, to move a potential medicine though this preclinical

process. Drug developers colloquially call this the " Valley of Death. "

TRND will work closely with disease-specific experts on selected projects,

leveraging both the in-house scientific capabilities needed to carry out much of

the preclinical development work, and contracting out other parts, as scientific

opportunities dictate. Its strategies will be similar to approaches taken by

pharmaceutical and biotechnology companies, but TRND will be working on diseases

mostly ignored by the private companies. Importantly, TRND will also devote some

of its efforts to improving the drug development process itself, creating new

approaches to make it faster and less expensive.

If a compound does survive this preclinical stage, TRND will work to find a

company willing to test the therapy in patients. There are several stages to the

clinical trials process that can take several years before the safety and

efficacy of a new drug is determined. FDA will only approve a drug for general

use after it passes these trials. The clinical trials process is also expensive,

but the failure rate is lower at this stage.

" NIH traditionally invests in basic research, which has produced important

discoveries across a wide range of illnesses, " said NHGRI Acting Director Alan

E. Guttmacher, M.D. " Biotechnology and pharmaceutical companies have enormous

strength and experience in drug development, but to maximize

return-on-investment work primarily on common illnesses. TRND will develop

promising treatments for rare diseases to the point that they are sufficiently

" de-risked " for pharmaceutical companies, disease-oriented foundations, or

others, to undertake the necessary clinical trials. NIH's goal is to get new

medications to people currently without treatment, and thus without hope. "

NIH already has many components of the drug development pipeline within its

research programs. TRND will begin its work in collaboration with the NIH

Chemical Genomics Center (NCGC), a center initially developed as part of the NIH

Roadmap for Medical Research. NCGC has developed a robotic, high-throughput

screening system and a library of more than 350,000 compounds that it uses to

make basic discoveries and probe cellular pathways. NCGC also has developed a

team of researchers skilled in developing assays representing disease processes

that can be tested in its screening system, and has extensive experience

building collaborative projects with investigators from across the research

community. Molecules with potential therapeutic properties that emerge from the

NCGC screening process could be fed into the TRND drug development pipeline.

" With this new funding, TRND will develop teams of scientists who can do the

hard work of optimizing chemicals that we or others discover that may treat rare

diseases and turn them into actual drugs, " said NCGC Director P.

Austin, M.D., who is also the Senior Advisor for Translational Research to the

NHGRI Director. " This will still be hard work and it will take time and produce

failures. Unlike traditional drug development, however, where only successes are

published, we will publish our failures as well, so everyone in the drug

development community can learn from them. That alone could be revolutionary. "

If all the preclinical hurdles can be crossed, a possible treatment must still

be tested in a series of clinical trials. TRND will seek to take advantage of

several NIH resources that can help launch human studies, including the NIH

Clinical Center, the NIH Rapid Access to Interventional Development (NIH-RAID),

and the Clinical and Translational Science Awards (CTSA) program.

External Partners

Numerous obstacles impede the development of new drugs for rare and neglected

diseases. In addition to the reluctance of private companies to risk their

capital on a potentially low return, relatively few basic researchers study rare

diseases, so the underlying cause of the illness frequently remains unknown.

And, because rare diseases are rare, researchers often have difficulty

recruiting enough people with the disorder to participate in a clinical trial

once a candidate compound reaches the stage where it can be tested in people.

Moreover, for many rare diseases, the natural history of the disease is poorly

understood, so researchers lack the needed clinical measures (such as blood

pressure) that can demonstrate whether a treatment is working.

To address these difficulties, TRND will seek a wide range of collaborations

with academic researchers, as well as partnerships with patient advocacy

organizations, disease-oriented foundations and others interested in treatments

for particular illnesses. TRND's leaders hope that the collaborations will help

lay the groundwork for clinical trials once that point in drug development is

reached.

TRND is currently setting up an oversight process to help it decide which

projects that address thousands of rare and neglected diseases will be pursued.

Leadership currently envisions a small number of diseases being studied each

year, with strict criteria used to determine which molecules will be studied for

which diseases. NIH expects to use existing intellectual property policies to

transfer licenses for TRND-discovered drugs to private companies or others for

development, clinical testing and marketing.