Drug Resistance in Malaria an Industry Perspective

1
Drug Resistance in Malaria an Industry
Perspective

• Heiner Grüninger, Global Program Head Tropical
  Medicines
• Novartis Pharma Development, Basel, Switzerland
• All-Party Parliamentary Group on Malaria, London,
  June 24, 2009

2
Novartis experience based on 235 mio. treatments
(cumulative) deployed since 2001

• Total deliveries 2008 74 mio. Tx
• Top 10 countries
• Tanzania 15.9
• Uganda 11.4
• Kenya 6.9
• Mozambique 6.3
• Nigeria 4.7
• Malawi 4.5
• Ethiopia 4.1
• Angola 3.0
• Benin 2.8

worldwide 54 countries deploying ACTs of which 45
Coartem
2
3
Artemisinin Combination Therapies (ACTs)for
Uncomplicated P.falciparum Malaria

• WHO recommends ACTs as first-line treatment
  because
• Limited (if any) resistance to artemisinin
  derivatives
• Artemisinin derivatives act rapidly, with short
  half-lives
• Rapid clearance of parasitemia and symptoms
• Limits selection of resistant parasites
• Combining with longer half-life partner drug
  provides high long-term cure rate with short
  treatment course

http//www.who.int/malaria/docs/TreatmentGuideline
s2006.pdf
4
WHO malaria treatment guidelines give criteria
for efficacy and for policy change

• Efficacy criteria
• ... new recommended antimalarial medicine should
  have cure rates 95 in assessed clinical trials
  ...
• Faliure criteria
• ... change anti-malarial treatmnet policy when
  cure rates fall below 90 (28days, PCR
  corrected)...

5
Coartem 28-Day PCR-Corrected Cure Rates gt 95 in
various endemic regions
a
a Uncorrected cure rate http//www.fda.gov/ohrms/
dockets/ac/08/briefing/2008-4388b1-02-Novartis.pdf
.
6
Treatment Failure Reports

• Each failure report followed up through
  industrys mandatory pharmacovigilance process
  (individual patients).
• Treatment failures can be caused by reasons other
  than resistance (Vestergaard Ringwald, 2007)
• Insufficient blood concentration of drug
• Drug cause
• Patient cause
• Diagnosis
• No malaria presumptive treatment
• New infection (not recrudescence) PCR
  confirmation
• Sometimes failure reports cannot be associated
  with a patient i.e. report is more a general
  impression than a documented fact
• - - -
• Studies showing reduced susceptibility / delayed
  response to artemisinins from the Thai-Cambodian
  border ongoing dialogue with Mahidol University
  / Oxford groups

7
Summary

• Follow up each treatment failure report
• Continue to perform studies assessing efficacy
  and effectiveness of Coartem (3rd parties and
  industry-led)
• Cooperate and exchange data with global
  initiatives for resistance monitoring (WHO,
  WWARN) e.g. yearly report on resistance to FDA
  (own data and literature), regular updates on
  safety and efficacy to other HAs
• Dialogue with Mahidol University / Qxford groups
  in Thailand to better understand mechanisms of
  reduces susceptability / delayed response to
  artemisinin derivatives
• Perform RD for novel anti-malarials - e.g.
  Novartis Institute for Tropical Diseases,
  Singapore together with Welcome Trust, MMV and
  others.