Orphan Drug status in India and Orphan drug status worldwide.

1. ORPHAN DRUGS
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2. DEFINITION
• “The Orphan Drug Designation program provides orphan status to
drugs and biologics which are defined as those intended for the safe
and effective treatment, diagnosis or prevention of rare
diseases/disorders.”
• The so-called 'orphan drugs' are intended to treat diseases so rare that
sponsors are reluctant to develop them under usual marketing
conditions.
• Because the manufacturer wont be able to recover the costs incurred,
& it remains in the phase 3 clinical trial , even after the approval from
the Ethics Committee.
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3. WHAT IS ‘RARE’ ?
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4. oDepending on the frequency of a disease in the
general population:
"Rare" means "less than 1 patient per xxx people."
oDefinition is arbitrary. Authorities in different countries or regions use
different cut-off values:
• WHO defines an incidence of 0.65-1/1000 as ‘Rare’
• US defines <2,00,000 (1/1500) patients as ‘Rare’
• EU defines <5/10,000 as ‘Rare’
• Japan defines <50,000 as ‘Rare’
• Australia defines <2000 as ‘Rare’4/8/2015 4

5. ACTS & REGULATIONS
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6. • ORPHAN DRUG ACT-The Orphan Drug Act (ODA) of
January 1983, passed in the United States, is meant to
encourage pharmaceutical companies to develop drugs for
diseases that have a small market
• Rare Diseases Act, 2002- establish the Office of Rare Diseases. It also
increased funding for the development of treatments for patients with rare
diseases.
• European Union(EU)- Committee on Orphan Medicinal Products- broader
definition than that of the USA, in that it also covers some tropical diseases
• The Humanitarian Use Device (HUD) program designates a device that is
intended to benefit patients by treating or diagnosing a disease or condition
that affects fewer than 4,000 individuals in the United States per year.
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7. 4/8/2015 8

8. • Orphan Designated Drugs in Clinical Phase: 400
• Marketed Orphan Designated Drugs: 281
• Highest Number of Drugs in Phase-2 Trial: 231
• US Dominates Clinical Trial Process: 350 in Pipeline (Research till
Registration)
• Indication for Clinical Trials for Orphan Drug: More than 30% for
Cancer Treatment
• Key Market: US (Sales > US$ 40 Billion)
IMPACT OF THE ACTS
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9. INDIAN PERSPECTIVE
• About 6000-8000 rare diseases, mostly genetic in nature.
• Initial estimation- over 31 million Indians are suffering from rare
diseases
• Taking the lower limit of global prevalence estimate, populous nations
like India and China should have more than 70 million rare disease
cases each.
• With a rare disease population estimated to be around 72,611,605 and
with little in place so far, India represents a lucrative market to
developers and pharma looking to expand their orphan operations.
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10. 4/8/2015 11

11. ORGANISATION FOR RARE
DISEASES INDIA (ORDI)
• Launched on Feb. 18, 2014
• Theoretically, 400 US FDA & 80 EMA approved orphan drugs- Available
• Practically, most are either not accessible to most patients in India or are
unaffordable
• It is ORDI’s mission and hope to make these and new approved orphan
drugs easily accessible and affordable to patients with rare diseases in India.
• Currently, drug developers in India are receiving no formal incentives from
the Government and hence are more focused on developing affordable
drugs
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12. COMPARISON OF ORPHAN AND
ESSENTIAL DRUGS
Aspect Essential drugs Orphan drugs
Concrete policies
in place since
1977 worldwide 1983:USA
2000: EU
Primary focus Public health Individual patient
Initiated by WHO & member states USA, EU, Japan,
Australia
Criteria Drug driven Disease driven
Policies aim to
provide
established medicines new medicines to yet
untreated patients
Economics Cost effectiveness,
sustainable & affordable access
High prices per patient
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13. PRIORITIES IN BRINGING DRUGS TO
PATIENTS
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14. PREVALENCE OF RARE
DISEASES
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15. CLINICAL TRIALS OF ORPHAN DISEASES
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16. Scientific Limitations
• Due to the rarity of the disease, a statistically powerful study with a
high sample size may not be feasible. "Statistical significance" may be
limited.
• Two studies (as otherwise typical) may not be feasible, because the
existing patients may hardly be sufficient to fill one study.
• Prognostic factors or disease course indicators might not be known.
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17. Use of Placebo
• When there is no treatment and the safe investigational drug is the
only (even if only theoretical) hope
– how can we justify not giving it?
• When the disease will inevitably create damage
– how can we justify withdrawing concurrent treatment in order to
have a "clean" placebo-controlled study?
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?!

18. HOW TO APPLY FOR ORPHAN
DRUG DESIGNATION
A sponsor shall submit two copies of a completed, dated, and signed request
for designation that contains the following:
1) A statement that the sponsor requests orphan-drug designation for a rare
disease or condition
2) The name and address of the sponsor; the name of the sponsor's primary
contact person
3) A description of the rare disease or condition for which the drug is being
or will be investigated, the proposed use of the drug, and the reasons why
such therapy is needed.
contd..
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19. HOW TO APPLY FOR ORPHAN
DRUG DESIGNATION- Contd..
4. A description of the drug, to include the identity of the active moiety, all relevant
data from in vitro laboratory studies, preclinical efficacy studies.
5. Where the sponsor seeks approval of an already approved orphan-drug, stating an
explanation as to why the proposed variation in his drug may be clinically superior
to the first drug.
6. A summary of the regulatory status and marketing history of the drug in the
United States and in foreign countries
7. Documentation, with appended authoritative references
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20. CHALLENGES FACED BY ORPHAN
DRUGS
• Difficulties in attracting public and private funding for research and
development
• Insufficient numbers of research participants for clinical studies
• Lack of knowledge and training for many rare diseases
• Lack of adequate expertise and review by authorities
• Deficient diagnostic systems
• High price of "orphan drugs"
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21. Development of Orphan drugs is costlier because:
The limitations of medical and scientific knowledge related to
the pathogenesis
A limited market
High research and manufacturing costs (50 to 80 per cent of
rare diseases are from genetic origin)
 Use of high tech products genetic therapies,
cellular therapies, recombinant proteins
Impossibility of patenting certain ingredients
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22. INCENTIVES
The incentives include:
• Funding towards investigation
• Tax credit for clinical research
• Waiver of fees for new drug application
• Market exclusivity of “Orphan drugs”
• Accelerated approval or fast track or priority review, may also be
available for sponsors of orphan drugs.
• Enhanced patent protection.
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23. EXCLUSIVITY PERIOD
COUNTRY EXCLUSIVITY TME (YEARS)
USA 7
JAPAN 10
AUSTRALIA 5
EUROPE (EU) 10
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24. COMPANIES INVOLVED IN THE
MANUFACTURE OF ORPHAN DRUGS
 Pfizer
 GlaxoSmithKline
 Novartis
 Sanofi Aventis
 Johnson and Johnson
 Bayer
 Orphan drug specialists
- Genzyme
- Actelion
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25. ORPHAN DRUGS AND MARKET PLAYERS
DRUG COMPANY THERAPEUTIC
INDICATION
Zavesca (miglustat) Actelion Pharmaceuticals US, Inc Type 1 Gaucher’s disease
Trisenox (arsenic trioxide injection) Cephalon, Inc. Acute promyelocytic leukemia
(APL)
Aldurazyme (Laronidase) Genzyme Ltd. Mucopolysaccharidosis I
Glivec (Imatinib mesylate) Novartis Philadelphia chromosome positive
chronic myeloid leukemia
Fabrazyme (Agalsidase beta) Genzyme Ltd. Fabry disease
Ventavis (iloprost) Actelion Pharmaceuticals US, Inc Pulmonary arterial hypertension
(WHO Group I) in patients with
NYHA Class III or IV symptoms.
Litak (cladribine) Lipomed Hairy cell leukemia
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26. CLASSIFICATION OF ORPHAN DRUGS
ACCORDING TO INDICATIONS AND COUNTRIES
DRUG INDICATIONS COUNTRY
Acetylsalicylic acid Polycythemia Vera Europe
Tobramycin Inhalational Powder/
Solution
Cystic Fibrosis
Pneumonia due to Pseudomonas
Aeruginosa
US
Europe
Desipramine Chlorhydrate Rett Syndrome Europe
Indomethacin Patent Ductus Arteriosus Japan
Histamine Dihydrochloride Acute Myeloid Leukemia
Acute Erythroid/Promyelocytic
Leukemia
Europe
USA
4/8/2015
Contd..

27. CLASSIFICATION OF ORPHAN DRUGS ACCORDING TO
INDICATIONS AND COUNTRIES- Contd..
DRUG INDICATIONS COUNTRY
Adrenomedullin (AM/ADM) Acute Lung Injury Europe
Acadesine B- Cell leukemia
Multiple Myeloma
Europe
Afamelanotide Solar Urticaria
Familial Benign Chronic Pemphigus
Europe
USA
Aclotine (Human Antithrombin III) Congenital Antithrombin III
Deficiency
France
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28. ORPHAN DRUGS IN INDIA
• The Hyderabad based NATCO Pharma’s novel anti-cancer drug,
NRC-AN-019 has received “ Orphan Drug Designation” from the
US-FDA for 3 indications-
1. Glioma
2. Pancreatic Cancer
3. Chronic Myeloid Leukemia
contd…
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29. ORPHAN DRUGS IN INDIA- Contd..
• Troikaa Pharmaceuticals, Ahmedabad manufactures following
orphan preparations:
1. Tachyban ( Adenosine injection)
2. Hemaprot (Aprotinin injection)
3. Neopam ( Pralidoxime injection)
4. Narcotam ( Naloxone hydrochloride injection)
5. Cyan SOS (Cyanide antidote kit)
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30. THE ORPHAN DRUG PIPELINE
ONCOLOGY- BRAND NAME GENERIC NAME
Istodex Romidepsin
Yondelis Trabectedin
Onrigin Laromustine
CENTRAL NERVOUS SYSTEM-
BRAND NAME GENERIC NAME
Zenas Amiframpidine
ITI 111 Midazolam
ANTI-INFECTIVES
BRAND NAME GENERIC NAME
Cayston Aztreonam Lysine
ABthrax Raxibacumab
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31. RECENT DEVELOPMENTS IN REGULATING ‘ORPHAN
DRUG’ APPROVAL
• The US FDA & EMA- announced a more streamlined process to help
regulators identify and share information in a better way, throughout
the development process of orphan drug and biologic products.
• If an orphan product was granted designation on the exact same day in
both the US and EU, the sponsors must submit separate reports to their
respective regulatory agency.
• Use of one annual report will also benefit sponsors by eliminating the
duplication of efforts and by simplifying the process
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32. CONCLUSION
• Orphan drugs may help pharma companies to reduce the impact of
revenue loss caused by patent expiries of blockbuster drugs.
• The new business model of orphan drugs offer an integrated healthcare
solution that enables pharma companies to develop newer areas of-
Therapeutics
Diagnosis
Treatment
Monitoring and
Patient Support
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33. THANK YOU
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