The document discusses drug repurposing as a method of finding new uses for existing drugs, which can significantly reduce development costs and timelines. It highlights various successful examples of repurposed drugs, such as thalidomide for multiple myeloma and celecoxib for colorectal cancer, and outlines the benefits of repurposing, including safety and lower risk. The conclusion emphasizes the potential of drug repurposing to enhance pharmaceutical product pipelines and provide new treatments for serious diseases.

1. Drug Repurposing-Amazing
Opportunity
Dr. Seema Kohli
HOD-Pharmacy Deptt.
KN Polytechnic College, Jabalpur, MP
Mission Star Conference- 07.06.2020
4.00pm

2. Introduction
• Establishing other new medical usages for
already known drugs, including approved drugs.
• Drug repurposing or repositioning lies in
repurposing an active pharmaceutical
ingredient for a new indication that is already
on the market.
• Drug repurposing is a promising approach and is
mainly applied for the treatment of rare genetic
diseases, and it offers significant benefits to the
pharmaceutical industries.

3. History of Repurposing
• In mid 2000s sildenafil for angina was repositioned to
erectile dysfunction and thalidomide for morning sickness
was repositioned to multiple myeloma. The success created
a big interest in repurposing which resulted in the
formation of many repurposing focused startup companies.
• Drug repurposing has since been extended to include active
substances that failed clinical phase of their development
due to their toxicity/insufficient efficacy, or drugs
withdrawn from the market.
• Few examples include Chloroquine was a well-known
antimalarial compound synthesized in the year 1934 and
was later targeted towards many other diseases including
parasitic diseases, fever, lupus skin rashes, and recently
being useful for Corona Virus patients.

4. Repurposing Definition
• "At its simplest, drug repurposing is taking an
existing drug and seeing whether it can be
used as an effective treatment for another
condition.“
• “Repurposing generally refers to studying
drugs that are already approved to treat one
disease or condition to see if they are safe and
effective for treating other diseases”.

5. Why Drug Repurposing
• The usual drug development process may delay the
translation of discovery from bench to bedside.
• The repurposing of 'old' drugs is an attractive
proposition because it involves the use of de-risked
compounds, with potentially lower overall
development costs and shorter development
timelines.
• Drug repurposing was initiated with expanding interest
from pharmaceutical organizations and the
recognizable proof of different cheminformatics and
bioinformatics findings.
• Out of these, nearly 10% of repurposed drugs were
approved by regulatory bodies and 70% are in various
stages of clinical development

6. Drug Discovery Process
• Researchers identify particular cellular and genetic
factors that play a major role in each disease condition.
• The discovery and developmental stages of new drug
molecules include target identification (targeting
cellular and genetic markers associated with a particular
disease), target prioritization/validation (identification
of developed molecule that have an effect on selected
target), lead identification (molecules capable of
treating the disease), and lead optimization
(comparison of properties of various lead compounds
and selection of lead compound with the greatest
potential).

7. Drug Discovery Process

8. Drug Discovery & Drug Repurposing
• Preclinical studies which follow drug discovery ensure the safety of
the drug by laboratory and animal testing. After the preclinical
research, investigational new drug (IND) application is submitted to
FDA for permission to conduct clinical testing.
• Clinical research phase includes phase I, II and III studies and is mainly
to ensure safety and efficacy of drug in humans.
• Despite the huge investments and time-consuming processes, the
chances of the new drug molecule clearing all the drug approval
processes are often negligible.
• So, the drug manufacturing companies focus on other viable options
for drug research.
• Which defined drug repurposing as “studying the drugs that are
already approved to treat one disease or condition to see if they are
safe and effective for treating other diseases”.
• That is why drug repurposing is the need for all.

9. Pharmaceutical development
• Drug repurposing is an innovation stream of pharmaceutical
development that offers advantages for drug developers
along with safer medicines for patients.
• Several drugs have been successfully repositioned to a new
indication, with the most prominent of them being viagra
and thalidomide, which have generated historically high
revenues.
• Repurposing can be seen as a business opportunity for
pharmaceutical companies, weighing both challenges and
opportunities of repurposing.
• In addition, Repurposing can be extended profiling as a
lower-risk cost-effective repurposing model for
pharmaceutical companies and elucidate the novel
collaborative business opportunities that help to realize
repositioning of shelved and marketed compounds.

10. Various stages of drug
development and
drug repurposing

11. .

12. Nutraceuticals & Familial Dysautonomia
• Familial dysautonomia is a debilitating pediatric
disorder characterized by symptoms such as
cardiovascular problems, increased sensitivity to
pain and temperature, gastrointestinal dysfunction
and increased occurrence of pneumonia. If left
untreated, most children with the disease do not
live past the age of three.
• However, recent research have revealed that
common nutraceuticals can be combined to
prevent the mutated gene that causes FD from
being transcribed in patients’ brain cells. These
compounds include isoflavones, which are plant-
derived substances with estrogenic activity, and
EGCG, which is found in green tea .

13. CELEBREX (CELECOXIB) & COLORECTAL POLYPS
• The popular drug Celebrex known for its effectiveness in
osteoarthritis, a disease characterized by bone damage,
chronic pain, and decreased range of motion. The drug’s
mechanism of action involves selective inhibition of
COX-2 receptors, which cause inflammation in the body.
However, this condition is not the only one that can
come about when COX-2 receptors are overexpressed.
• Recent research has shown that COX-2 activity is
correlated with increased risk of colorectal cancers, and
that using drugs such as Celebrex can significantly
decrease the risk of additional polyp formation in
patients who have had colon cancer in the past).
Though Celebrex is not risk-free and carries with it some
chance of adverse cardiovascular reactions, the
discovery of its repurposed use has been a significant
milestone in colon cancer research.

14. METFORMIN & BREAST CANCER
• Metformin, a common diabetes drug that has
been manufactured at low cost for years, has a
long record of safety, effectiveness, and limited
side effects in diabetics.
• In the mid-2000s an interesting discovery was
made and published in the British Medical Journal:
patients taking metformin for diabetes saw a
significantly lowered risk for breast cancer .
Further investigation into this phenomenon is
ongoing at institution such as the Mayo Clinic and
University of Chicago, focusing on several other
types of cancer, as well .

15. METHROTREXATE & RHEUMATOID ARTHRITIS
(Dose adjustments to existing treatments)
The effects of certain drugs can vary greatly based on
dosage, making them ideal candidates for repurposing
research. Methrotrexate was developed as a
chemotherapy drug in the 1950s and has since been
administered at a very high dose to cancer patients.
At a low dose, and because of totally different
mechanisms of the drug, it has become a standard of
care for auto-immune diseases such as rheumatoid
arthritis . Researchers have since ironed the drug’s
alternative mechanisms through studies on juvenile
idiopathic arthritis .

16. THALIDOMIDE & MULTIPLE MYELOMA
(Dangerous originally, repurposed safely)
• One reason for the low success rate of novel drug
development is the high percentage of adverse side effects
found in late-stage clinical trials. However, failed drugs can be
repurposed for different diseases with new patient
populations that would not be affected by such side effects,
creating benefit for both pharmaceutical companies and for
patients.
• Most adults have heard about “thalidomide babies” born with
birth defects in the 1950s. however, they might not know that
this drug, developed as a treatment for morning sickness, has
some redeeming qualities. While it was dangerous in its initial
disease indication, this drug has been explored for its other
properties and has been proven effective in the treatment
of multiple myeloma, a devastating blood cancer and the
treatment of leprosy.

17. CHLOROQUINE & LUNG CANCER
(Combining new drugs with repurposed old drugs)
• Chloroquine, a drug that has historically been used
to treat malaria, has recently been combined with a
new drug, Tarceva, which kills lung cancer cells.
Tarceva only works for some patients, and the
cancer almost always becomes resistant after
prolonged exposure to the drug.
• However, the addition of chloroquine to the
treatment regimen appears to increase the number
of patients for whom Tarceva works, and helps it
work for longer.

18. RAPAMYCIN & PAEDIATRIC BLOOD DISEASE
(Repurposing generics for rare diseases)
• Rapamycin was just such a drug: originally
developed as a transplant anti-rejection drug,
it is now available generically.
• Through some fairly straightforward trials,
it was found to be an effective treatment for
the pediatric blood disease Autoimmune
Lymphoproliferative Syndrome (ALPS) due to
its immunosuppressant properties.

19. ITRACONAZOLE & CANCER
• The anti-fungal compound itraconazole was developed
in the 1980s, and suppresses fungal growth by inhibiting
membrane function in fungal cells . But a 2007 study
showed that the drug also has potent anti-cancer
properties .
• Further studies of itraconazole on its own, and
combined with other medicines, showed that it was an
effective treatment for cancers of the prostate, skin,
lungs, and other areas of the body. Clinical trials at
Johns Hopkins and Stanford University have yielded
positive results , and although the specific mechanisms
by which it works are unknown, this common antifungal
has made its way into the toolbox of oncologists across
the country.

20. ATRA & LEUKEMIA
• Another cancer treatment success story involves
the repurposing of all-trans retinoic acid (ATRA), a
chemical compound historically used in
medications that treat severe acne.
• Though it does not have anti-cancer properties
when used alone, ATRA has been combined with
traditional chemotherapy and to induce complete
remission in 90% of patients with acute
promyelocytic leukemia. The drug combination has
also been proven to significantly decrease the
chance of relapse among leukemia patients in
remission.

21. Drugs helpful in = Sars Cov2
• The US Food and Drug Administration (FDA)
approved limited emergency use for chloroquine and
hydroxychloroquine as a treatment for COVID-19.
• China has approved the use of Favilavir, an anti-viral
drug, as a treatment for coronavirus.
• The antiviral drug remdesivir gained emergency use
authorization (EUA) from the FDA on May 1, 2020,
based on preliminary data showing a faster time to
recovery of hospitalized patients with severe disease

23. Drug Repurposing in India
• Drug repurposing in India TB, HIV/AIDS, malaria, NTDs like
leprosy, lymphatic filariasis , visceral leishmaniasis ( kala-azar).
• Lifestyle diseases: diabetes, hypertension, IHD, cancers.
Reluctance of companies to invest in R&D of drugs for
infectious diseases and NTDs
• Drug repositioning in India Global initiatives based on public-
private partnership models: WHO special programme for
research and training in Tropical diseases (WHO/TDR)
Medicines for malaria venture, Global Alliance for TB Drug
Development, Drugs for Neglected Diseases.
• Paromomycin and miltefosine for kala-azar following trials in
India.
• Under the patent act of India, use of patent for a new
indication is not permissible for an already patented drug

24. Benefits of Drug Repurposing
• It’s Less Risky:
risks are better known and the chance of
failure due to adverse side effects is reduced.
• It’s Faster:
patients with terminal cancers, orphan
diseases, and other incurable conditions often
do not have a decade to spare.
• It’s Cheaper:
more patients will have access to and be able
to afford their repurposed medications

25. Barriers To Drug Repurposing
• Lack of Financial Incentives
• Undermines Existing Markets
• Legal and Intellectual Property Issue
• Still a Risky Business
• Scientists Rewarded for Originality

26. Conclusion
Drug repurposing is a promising approach and is
mainly applied for the treatment of rare genetic
diseases, and it offers significant benefits to the
pharmaceutical industries. In the current
economic climate, two factors may continue
impact into repurposing projects.
• the need to expand product pipelines with new
projects has become more acute, especially
with projects for which an element of the risk
has been removed.
• the pool of potential compounds abandoned for
strategic reasons is growing.

27. Conclusion
• Pharma industry is looking to explore the full
potential of their compounds at a much earlier
stage, perhaps even in late preclinical development,
offering additional opportunities for these
companies.
• Drug repurposing is expected to add value to the
product portfolio of the drug companies and
enhances the ability to bring new and affordable
treatment options for a number of serious and
neglected diseases.
• Since drug development involves multistage
process, time and money intense, thus, this type of
innovative ideas and novel concepts definitely will
expedite the drug development process.

28. References:
• Drug Repositioning (New Uses of Old Drugs) Dr. Amol
Khanapure, available at
http://www.authorstream.com/Presentation/doc18-
2055920-presentation1/
• D.J. Wallace, The history of antimalarials, Lupus5
(1_suppl) (1996) 2-3
• M. Schlitzer, Malaria chemotherapeutics part I: history of
antimalarial drug development, currently used
therapeutics, and drugs in clinical development,
ChemMedChem 2 (7) (2007) 944-986
• Rajesh Kumar a , Seetha Harilal, “Exploring the new
horizons of drug repurposing: A vital tool for turning hard
work into smart work”, European Journal of Medicinal
Chemistry, 182 (2019). 11602.
Continued…..

29. Now……
Some life examples of repurposing

30. Plastic bottle into plant-repurposing

31. Plastic spoons into lamp-repurposing

32. thank you
for listening