Hoodia, a case study 1963-2008

Hoodia, a case study

1963-2008

November 2008November 2008

Dr Vinesh Maharaj

Research Group Leader

CSIR, Biosciences

Hoodia Development Cycle

DiscoveryDevelopment: Clinical

and regulatory approval

Commercial Sales

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LeadHit Preclinical

Slide 2 © CSIR 2006 www.csir.co.za

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CSIR

What is Hoodia?

Hoodia is a novel method of weight management Hoodia is a novel method of weight management derived from the Hoodia plantderived from the Hoodia plant

•Based on formulations invented by CSIR

•processed herbal extracts

•purified chemical compounds or analogues


•purified chemical compounds or analogues thereof

•synthetic or natural

Hoodia: History of use

•Hoodia research was stimulated by traditional use of plant by San people

•Used by San people as substitute for food and water (Marloth, 1932: White and Sloan, 1937)

•Has an insipid taste and used to quench thirst (Pappe, 1862)


1862)

Hoodia in its natural habitatHoodia in flower

Hoodia:Early Research

19631963--19711971

• NFRI of CSIR launched a project to investigate food from the “veld”

• Nutritional value and long term toxicity studies was the focus of study

• Hoodia was one of several 100 plants


• Hoodia was one of several 100 plants• Prepared several extracts of the plant• Extracts tested in rodents• Appetite suppressant properties with weight

loss• No apparent side effects• Data kept confidential

Hoodia: Early Research

19831983--19861986

•Active isolated through bioassay guided fractionation•Fractions tested in vivo•Innovation made possible by acquisition of world-class instrumentation for structure elucidation


Biological assaying

Food consumption

10

15

20

25

30

Foo

d co

nsum

ptio

n (g

)

Vehicle

6.25


Dosage on days 1,2,3 given in mg/kg/day

0

5

1 2 3 4 5 6 7 8

Days

Foo

d co

nsum

ptio

n

6.25

12.5

25

37.5

50

Ref: Phytochemistry, 68, 2545–2553, (2007)

Biological assaying

Food consumption: Active vs fenfluramine

10

15

20

25

30

Foo

d co

nsum

ptio

n (g

)

Vehicle


Dosage on days 1,2,3 given in mg/kg/day• Active : 30 mg/kg• Fenfluramine: 15 mg/kg

0

5

Day -1

Day 1 Day 2 Day 3 Day 4 Day 5 Day 6 Day 7 Day 8

Foo

d co

nsum

ptio

n (g

)

Vehicle

Compound 1

Fenfluramine

Hoodia: Innovations19901990--19971997

•Additional studies

•Acute in vivo toxicity

•Attempted synthesis

•Efficacy confirmed in independent labs

•Cultivation of plants with confirmation of active in


•Cultivation of plants with confirmation of active in plant extracts

•New formulation for obesity control invented and patented




Commercial Sales

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CSIR CSIR/Phytopharm

Hoodia: Further development

•CSIR licensed patent to Phytopharm plc in UK

•CSIR/Phytopharm joint research programme focused on:

•GMP manufacturing

•Quality control


•Quality control

•Safety and efficacy

Hoodia: Manufacturing

• Botanical and Clinical Supplies Unit for the manufacture herbal extracts

• Manufacture extracts in compliance with GMP

• Material approved for clinical trials


Hoodia: Quality Control

• HPLC method developed for the quantitative analysis of steroid glycosides

• HPLC MS used to confirm the compounds• Method applied to the analysis of steroid glycosides in a range

of samples 100

761.557295.239

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601 457 313

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100761.557295.239

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601 457 313

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0

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%

28.38

2.55

1.85

3.45

24.034.42 22.7418.505.54

14.10

27.6325.19

31.94

30.77

28.93

37.0233.87

32.3734.45

35.19

38.12

40.3538.53

Time (min.)

Rel

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e in

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ity

0

100

%

28.38

2.55

1.85

3.45

24.034.42 22.7418.505.54

14.10

27.6325.19

31.94

30.77

28.93

37.0233.87

32.3734.45

35.19

38.12

40.3538.53

Time (min.)

Rel

ativ

e in

tens

ity

[M -

H2O

+ H

]+

-tiglate

701.517

-The

-tiglate

-Cym-Cym

-tiglate-tiglate

-H2O-H2O

50 100 150 200 250 300 350 400 450 500 550 600 650 700 750 800 850 900 950m/z

0

%

273.165

255.151239.153

313.254457.355

413.320395.313 557.424

601.456

861.630

Rel

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295

[M -

H2O

+ H

]+

-tiglate

701.517

-The

-tiglate

-Cym-Cym

-tiglate-tiglate

-H2O-H2O

50 100 150 200 250 300 350 400 450 500 550 600 650 700 750 800 850 900 950m/z

0

%

273.165

255.151239.153

313.254457.355

413.320395.313 557.424

601.456

861.630

Rel

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295295

Hoodia: Safety and efficacy

•Obtained preclinical data

•Acute and chronic in vivo toxicology studies

•pK data obtained

•In vitro toxicology, metabolism

•In vivo efficacy, 2 animal species


•In vivo efficacy, 2 animal species




Commercial Sales

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CSIR CSIR/PhytopharmMultinational


•Phytopharm further on licensed to Pfizer for further development and commercialization

•Completed early clinical studies

•Pfizer discontinued clinical development



•Phytopharm sub-licensed to Unilever

•Currently in development as a food ingredient for weight management

•Safety and clinical studies on-going

•Establishing a supply chain for product


•Establishing a supply chain for product

•Expect a commercial product in 2-3 years

Hoodia cultivation-Supply Chain


“..San people are custodians of an ancient body of traditional knowledge …related inter alia to human uses of the Hoodia plant …”,

“The CSIR acknowledges the existence and the importance of the traditional

Indigenous Knowledge & the CSIR/San Indigenous Knowledge & the CSIR/San AgreementAgreement

S A San Council visits CSIR facilities


and the importance of the traditional knowledge of the San people, and the fact that such body of knowledge, existing for millennia, predated scientific knowledge developed…”

S A San Council visits CSIR facilities

CSIR/San Agreement: NumbersCSIR/San Agreement: Numbers

CSIR and San agreed for CSIR to pay eight percent of all milestone payments it receives from its licensee, UK-based Phytopharm plc, as well as six percent of all royalties that the CSIR receives once the drug is commercially available.

Potential income into a San Hoodia Benefit Sharing TrustTrustees include:


Trustees include:•SA Department of Science and Technology•CSIR•San Representatives (≠ Khomani,!Xun, Khwe)•Other San in the southern African region•Working Group of Indigenous Minorities in Southern Africa

• Full involvement of South African scientists in development

• Transfer of state-of-the-art phyto-medicine production technology to South Africa

Hoodia Licensing: Benefits to SA


•Potential royalty revenue through licensing of patented technology; milestone payments linked to clinical trials•Global recognition of SA’s innovation capacity•Agroprocessing businesses established in SA for both commercial and community farmers

Summary of events

1963

CSIR includes Hoodia in research project on edible plants, based on ethnobotany

1971 Hoodia project mothballed, insurmountable technical problems

1983-1986 Technological advances. Scientific breakthrough at CSIR leads to discovery of active ingredient in Hoodia.

1986-1996 CSIR continues development of Hoodia, files world-wide patents to protect its invention of novel method of obesity control.


its invention of novel method of obesity control.

1997 CSIR licenses Phytopharm for further development of Hoodia

1998 CSIR publishes its Bioprospecting Policy, guaranteeing sharing of benefits with owners of Indigenous Knowledge

1998 Phytopharm sub-licenses Pfizer to complete Hoodia clinical development, obtain regulatory approval and commercialize

Summary of events cont…..1999 CSIR signs historical bioprospecting agreement with South African

Traditional Healers, invited by UN to present details at Lyon Summit on Trade and Development

2001 UK newspaper reporter questions CSIR-Phytopharm-Pfizer collaboration, without involvement of San

2002-2003 CSIR and San meet regularly to share Hoodia information; involve independent experts in workshops; negotiate benefit sharing agreement


24 March 2003

CSIR and San sign Hoodia benefit sharing agreement

2003 Pfizer discontinues clinical development

2004 Phytopharm sub licenses Unilever to continue development

Today Hoodia being developed as a food ingredient for weight management

Thank you!

Thank you!


Hoodia, a case study 1963-2008

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