Ranbaxy Laboratories Limited - Medicines for Malaria Venture · Ranbaxy as first line oral therapy...
Transcript of Ranbaxy Laboratories Limited - Medicines for Malaria Venture · Ranbaxy as first line oral therapy...
Ranbaxy Laboratories LimitedArterolane maleate + Piperaquine phosphate
Shailesh Pednekar Global Therapy ManagementMumbai – 30th Sept 09
Ranbaxy Overview
Global Presence
•Top 10 Global Generic Company
Unique Strengths & Capabilities•Entrepreneurial & Empowering
Vertically Integrated
•Manufacturing – DF and APITop 10 Global Generic Company• Sales in Over 125 Countries• 2008 Revenue: $ 1.7 Billion• 80 % International; 20% India
•Ground Presence in 49 CountriesGl b l T i h Gl b l Mi d
• Entrepreneurial & Empowering Culture
• Strong Presence in Emerging Markets : 58% of DF Sales
• Foray into Biosimilars and S i lt I j t bl
Manufacturing DF and API• 24 Plants in 11 Countries
• R&D• #1 Cumulative ANDA Filer from India• > 1400 R&D Personnel• World class Drug Discovery•Global Team with Global Mindset
• Over 12,000 Employees; Over 50 Nationalities
Specialty Injectables•Global Regulatory Prowess
• World‐class Drug Discovery Infrastructure
• NCE collaborations: GSK, Merck• Demonstrated NDDS capabilities
Largest pharmaceutical company out of Indiawith global reach and competencies across the value chain
Perhaps the largest front‐end in the generic industry
Other Emerging Markets
BRICS
• No. 1 in India • 43/54 countries in Africa• Large, reputed player in
CIS; growing rapidly• No. 6 in Brazil
No 5 in S Africa
43/54 countries in Africa• Latam & Asia Pacific:
long standing presence; good understanding; rrobust businesses
North America & Europe
• No. 5 in S. Africa rrobust businesses
North America & Japan
Europe
• Pioneer entrant from India
• Well established• 23/25 EU markets
• Strong local presence • Canada: New market,
growing rapidly
• No. 1 Generic player in Romania
Ground presence in 49 countries; products sold in 125
Background – RBx11160
Malaria is one of the most persistent killer diseases claiming more than 1 Million Lives every year. Majority being children and 40 % of world population at risk in more than 107 countries.
Anti‐malarial research has been one of the neglected researchAnti malarial research has been one of the neglected research areas in the world.
D i t il bilit d ti l bilit dDrug resistance , availability , production , scalability and affordability still remain concern areas.
MMV and Ranbaxy partnered for the drug development in year 2003 as a part of collaborative research program.
Cont…
Originally RBx11160 was being jointly developed by MMV and Ranbaxy as first line oral therapy for uncomplicated p.falciparumM l i l i f tiMalarial infection.
RBx 11160 Maleate ( Arterolane Maleate ) is a synthetic Trioxolaneand would provide an alternate to plant derivative compounds.
Subsequently the development of the drug was doneSubsequently , the development of the drug was done independently by Ranbaxy with a goal to develop a once daily FDC that will retain all attributes of ACT’s.
Partner Drugs was identified as Piperaquine phosphate.
The product is targeted to have a affordable cost of therapy and convenient dosing .
Targeted product profile
Parameter TargetCombination 2 highly active drugs
(1 short half life and 1 long half life)(1 short half-life and 1 long half-life)Efficacy ACPR day 7 = 100% & day 28 PCR-corrected ≥
95%ACPR=Adequate Clinical & Parasitological Response
Gametocytocidal at least one drug in combination
Resistance no resistance at presentSafety comparable to present drugs or better
Dosing once daily for ≤ 3 daysCo-formulated must be a fixed dose combination
Shelf life ≥ 2 yearsCost of Treatment ≤ $1.00 dollar for an adult
Status of development
Pre-clinical Phase I Phase II
Arterolane
Ph II Ph III
Pre-clinical Phase I
Filing PM CT
ComboArterolane + PQP Arterolane + PQP
Ph II Ph III Filing PM CT
Combo
Pre-clinical Phase I Phase II*
Piperaquine (PQP)
CT
CompletedOngoingOngoingTo be done
Clinical Trials with ArterolanePhase of
TrialStudy Population
(N)Country Doses in mg Findings
Young males (72) UK 25-600 mg Well tolerated
Phase I
(Safety
g ( )
(18 -45 Years)
g
(Rising single)
25-200 mg
(Rising multiple)
In healthy Vol) Elderly males & females (24)
(65 and above)
UK 100 mg (single) Well tolerated
Y l & Th il d 100 W ll t l t d PKYoung males & females (16)Pk Study – Health V
Thailand 100 mg
(single cross-over)
Well tolerated. PK similar to Caucasians
Phase II Patients (72) Thailand 25-200 mg Improved parasite
Proof of Concept
( )
Single Dose ( POC )
g
(Single)
p pclearance at 200 mg
Patients (16)
Pk Study
Thailand 100 mg
OD x7
7-day ACPR – 100%
Dose Range finding study
Patients (230)(Dose Range Finding )
Thailand India
Tanzania
50-200 mg
OD x7
Median PCT ~32 hours at 200 mg
Clinical Trials with PQP
Phase of Study Country Doses in mg FindingsTrial Population
(N)
Phase I Young Switzerland 500-1500 mg Well tolerated.
Safety In healthy Volunteers
gmales (72)
g
500-1500 OD x3
Mild AE’s
(nausea, vomiting & abdominal OD x3pain)
Published Data
Patients Vietnam
Cambodia
640 BD x2 or 640 OD
ACPR > 95%
(as non-GMP Artekin)
Cambodia
Thailand x3
Arterolane maleate + PQP ‐ Clinical DataPhase of
TrialStudy
Population (N)
Country Doses mg Findings
Phase I
( Safety )
Young males (70)
(Rising Single Dose)
Switzerland 100mg + 500mg upto 200mg + 1000mg (single)
Well tolerated.
Dose)
Young males (24 – 8 vol/cohort)
India (In-house -CPU,
Co-administration of 100mg + 500mg to 200 mg + 1000
• Well tolerated. • There seems to be a
positive interaction
(Rising Multiple Dose)
Noida) mg of RBx 11160 maleate + PQP
Multiple dose
between RBx 11160 & PQP .
• 750 mg PQP dose looks to be, just the right dose for a 3-Day regimen
Phase II
(Safety and Efficacy)
13-65 years (240) India, Thailand
Co-administration of 150mg + 750mg X 3 days
• Study completed• Well tolerated; efficacy
comparable to CoartemEfficacy) X 3 days compa able to Coa tem
Clinical Trial Sites
India
Thailand
Bangladesh
Africa ?
Status of development – Trial Timelines
S No. Trial Title Expected C l iCompletion dates
1 Phase III Trial of FDC of arterolane End 20101 Phase III Trial of FDC of arterolanemaleate and PQP vs Coartem in India and SE Asia (P.fal)
End 2010
2 Phase II Paediatric trial in India (P.fal)
End 2010(P.fal)
3 Phase II trial in patients with Vivaxmalaria in India in Adult patients
End 2010
Future Collaborative Clinical Trials
1. Second Phase III (Pf) Trial
– Africa and India
2. Arterolane efficacy trial in artemisinin resistant patients
– Western Cambodia
3. Phase II, dose ranging trial (Pf) Trial
– African children
4. Phase III, P. vivax trial
– India, SE Asia and Latin America
Queries?
For any specific commercial queries : Mr. Shailesh Pednekar ‐ Business Lead E‐mail : [email protected]
For any specific technical queries : Dr. Nilanjan Saha ‐ Technical Lead E‐mail : [email protected] mail : [email protected]
Thank You
Back Up SlidesBack Up Slides
Arterolane maleate + PQP ‐ Clinical Data
Phase of Trial
Study Population (N)
Country Doses mg Findings
Bio Avb Study with Adult formulation
Young Male volunteers
India(In-house, CPU, Noida)
150mg + 750mg (Single Dose FDC )
Comparative bioavailability
)
Bio Avb Study with Paediatricformulation
Young Male volunteers
India(In-house, CPU Noida)
37.5 mg + 187.5 mg(Single Dose FDC )
Failed formulation (Formulation issue )
CPU, Noida)
Repeat Bio Avb Young Male India 37.5 mg + 187.5 mg Showed Comparative Study with Paediatricformulation
volunteers (In-house, CPU, Noida)
(Single Dose FDC ) bioavailability