Seqens eBook - 20

DRUG DEVELOPMENT

with Fragile-X syndrome, a genetic disorder that leads to cognitive
disabilities. It is being evaluated in clinical trials.7
Recent efforts have focused on identifying existing drugs that can
be repositioned or repurposed as antibiotics for the treatment of
infections caused by drug-resistant bacteria. In late 2016, Researchers
at NIH's Institutes of Health's National Center for Advancing
Translational Sciences (NCATS), Clinical Center and National Institute
of Allergy and Infectious Diseases (NIAID) reported that they had
tested approximately 4,000 approved drugs and other biologically
active compounds for antibiotic effectiveness against drug-resistant
bacteria using a newly developed screening method. They identified
25 compounds that suppressed the growth of two drug-resistant
strains of Klebsiella pneumonia, which have caused fatal infections in
hospitals across the US.8
In August 2017, Mohamed Seleem and colleagues at Purdue
University received a $1.6 million grant from NIH to determine if two
existing drugs can be repurposed to treat drug-resistant bacteria.
Ebselen is a clinical molecule that is potentially effective against
methicillin-resistant Staphylococcus aureus (MRSA), while auranofin,
which is FDA-approved for the treatment of unresponsive rheumatoid
arthritis, appears to be effective against Clostridium difficile.9

Widespread Effort
In addition to government organizations such as NCATS, there is a
broad array of groups focused on identifying new uses for existing
drug candidates and approved products. Public-private partnerships,
nonprofits, academic researchers and companies, including Big
Pharma firms and startups with advanced technologies specifically
designed to facilitate DRPx activities, are all involved.
Cures Within Reach is perhaps the most well-known nonprofit group
focused on drug repurposing. UK-based Findacure and Globalcures
are others. Examples of public-private partnerships include the Center
for Drug Repurposing (operated jointly by Ariel University and Drug
Rediscovery Ltd.) and the Drug Repurposing Hub (a collaboration
between the Broad Institute Cancer Program, the Center for the
Development of Therapeutics, and the Connectivity Map group); and
The Repurposing Drugs in Oncology (ReDO) project.
Startups with proprietary screening, computational and datamining technologies include Biovista, GVK Bio, NuMedii, Excelra, and
Recursion Pharmaceuticals, among others.
A large number of academic research groups are also actively seeking
to find new treatments for rare diseases using existing compounds.
In addition to Seleem's group at Purdue University, other groups can
be found at the University of Pennsylvania, the Houston Methodist
Research Institute, the University of Texas Health Science Center,
McGill University and many other academic institutions.10
Large pharmaceutical companies have formed partnerships with
many of these organizations to help facilitate the repurposing and
repositioning of their existing products. For instance, Sanofi Genzyme
signed a research agreement with Recursion and Astellas Pharma has
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formed strategic collaborations with Excelra, Biovista and NuMedi.2
NCATs works with pharmaceutical companies to make data and
sample of existing compounds available to academic researchers
at no cost for evaluation with the intention of repositioning or
repurposing them as new treatments.10 Even publishing companies
are becoming involved. In late 2016, Elsevier began collaboration
with Findacure, providing analytics tools and access to literature data
on known compounds.11

Regulatory Pathway
The regulatory pathway used to repurpose/reposition existing
drugs is typically the 505(b)(2) application. The 505(b)(2) new drug
application (NDA) was created by the Hatch-Waxman Amendments
of 1984 and allows the filer to use data for previously approved
("reference" or "listed") drugs not developed by the NDA applicant.
Changes that can lead to submittal of a 505(b)(2) application can
be related to the formulation, dosing regimen or indication, among
others.12
In the US, several pieces of legislation have been introduced that
address drug repurposing,12 including the Modernizing Our Drug
& Diagnostics Evaluation and Regulatory Network Cures Act, or
"Dormant Therapies" Act, introduced in the House in 2013 (H.R.3116),
provides patent and exclusivity protection enhancements and is a
reworking of the MODDERN Cures Act of 2011 (H.R.3497). The Orphan
Product Extensions Now Accelerating Cures & Treatments (OPEN
ACT) was introduced in the House (H.R.1223) in 2017 and is designed
to encourage drug makers to repurpose existing drugs for rare and
pediatric diseases.

The Promise of Big Data and
Computing Power
When looking at the potential of an existing compound as a treatment
for a new indication, scientific rationale, clinical viability, commercial
viability and regulatory path all must be considered, according
to Deshpande.1 The indication must be a true clinical need, the
mechanism of action must be appropriate, formulation and delivery
with high bioavailability and efficacy must be manufacturable in
a cost-effective manner and the market dynamics (competition,
pricing, reimbursement etc.) must be appropriate.
Big-data analytics, advanced modeling software and high throughput
screening techniques are making it possible to systematically and
rapidly evaluate the thousands of existing compounds against
different indications and cell lines to find molecules that show
promise for biologically matching disease targets.13 Similarly,
significant advances have been made in the instrumentation and
techniques for physically analyzing genomic data, which is allowing
the identification of more specific disease targets for subgroups
of patients.11 Advances in the field of transcriptomics, or the study
of active genes within cells, are also allowing the investigation of
transcriptomic signals resulting from specific drugs.6
Biovista, for instance, maps the connections between drugs, molecular
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Seqens eBook

Table of Contents for the Digital Edition of Seqens eBook

Contents
Seqens eBook - 1
Seqens eBook - Contents
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