FIXED DOSE COMBINATION (FDC)
PRODUCTS OVERVIEW
Tugrul T. Kararli, Ph.D. MBA
President and Founder
PharmaCircle LLC
OUTLINE
• Rational
• Marketed and Developmental stage FDCs
– Global picture
– Large pharma
– Ther. categories
– Delivery Routes/DD technologies
• Conclusions
FIXED DOSE COMBINATIONS (FDC)
RATIONAL
• Improved patient compliance: Simplified disease
management for chronic diseases (e.g. HIV,
asthma, diabetes, lipid regulation, hypertension,
etc.)
• Better efficacy: Synergistic mechanisms,
improved ADME & drug resistance
• Simplified/cost effective handling & distribution
especially for HIV drugs
• Effective LCM strategy: New products from
proven molecules; patent/market exclusivity, may
also combine formulation patent exclusivity
MARKETED FDC PRODUCTS
n=1597
MANY OLD MARKETED PRODUCTS
-Cough and cold
-Topicals, etc.
MARKETED FDC PRODUCTS
Includes, new combinations, indications and formulations and territories
Exclude Generic/OTC and approvals, n=230
ØGrowing number of Rx FDCs approved since 90’s
Ø90% with 2 molecules and only 7% with 3 molecules
1990
ROUTES FOR MARKETED FDC PRODUCTS
Includes, new combinations, indications and formulations and territories
Exclude Generic/OTC and approvals n=206
Ø25of based DD technology
Ø83% Tablet
80% Topicals
MARKETED ORAL COMBO PRODUCTS
Includes, new combinations, indications and formulations and territories
Exclude Generic/OTC and approvals , n=30
Majority Matrix MR Tablets
25% (n=30) of all oral (n = 120) based DD technology
APPROVALS VS. INDICATIONS (GLOBAL)
Includes, new combinations, indications and formulations and territories
Exclude Generic/OTC and approvals , n=234
Pain Management and
Cardiovascular Local Anesthesia
ØHypertension
ØLipid Lowering Infections
ØHIV/AIDS
ØBacterial
infections
Respiratory
Endocrine
ØAsthma
ØDiabetes
ØCOPD
ØLipid lowering
Womens’s Diseases
ØContraceptives
Skin Diseases
ØOsteoporosis
ØAcne
ØMenopause
ØSkin Infections
ØAnti-inflammatory
CARDIOVASCULAR FDCs
n=37
78% for Hypertension
Majority Hydrochlorothiazide combinations
Renin Inhibitor, AT I R and AT II R antagonist, FDCs are likely to
Ace Inhibitors, Ca+2 Channel blocker, etc.
improve adherence in
Hydroxymethylglutaryl-CoA a range of settings,
Reductase Inhibitor combos : but uncertainty
Vytorin, Caduet, Simcor ER,
Tredaptive, Advicor, etc. remains about the
size of these benefits
FDCs for INFECTION
n=35
Viral Infections; HIV/AIDS,etc. • Old gold standard for
HIV: Combivir an FDC of
zidovudine and
lamivudine -2xday
• Newer FDCs with once
daily dosing and
improved tolerability
and toxicity profiles
• Simplified
dosing/handling-
improved compliance,
better disease control
FDCs for ENDOCRINE/METABOLISM
n=20
Diabetes FDCs are likely to
improve adherence in
a range of settings,
but uncertainty
remains about the
size of these benefits
ASTHMA/COPD FDCs, n=30
FDA recommends the use of FDCs containing an inhaled corticosteroid
and a LABA because of the difficulty of ensuring compliance with both
medications when they are administered separately
ØSymbicort (AZ)
Advair
ØFOSTER Modulite (Chiesi)
• Advair (GSK) and
Symbicort (Astra
Zeneca) combined sales
$9.5bil-50% of
Inhalation market
%18b-20 products
FDC PIPELINE (GLOBAL)
n=391
ØMajority with
2 molecules
ØOnly 18 with
have 3 mol.
(HIV, Pain,
Diabetes, etc.)
Ø1 has 4
molecules (HIV)
ROUTES FOR FDC PIPELINE
n=332
Oral
ORAL FDC PIPELINE
n=87
Oral MR
FDCs MARKETED by LARGE PHARMA
Marketed since 1990 (no OTC), n=58
Novartis
FDC PIPELINE - LARGE PHARMA
n=45
Novartis has been most active
TOP SELLING FDC PRODUCTS
Name /Form Molecules Indication Approval Year/ Sales 2009
Company ($Mil)
Advair Discus/DPI/HFA fluticasone/salmeterol Asthma/COPD 2000/GSK 7800
Hyzaar/Cozaar losartan/HCT Hypertension 1995/Merck & Co. 3561
Truvada emtricitabine /tenofovir HIV/AIDS Gilead/2004 2490
Atripla Tablets efavirenz/ emtricitabine/ HIV/AIDS 2007/Gilead/BMS 2382
tenofovir
Vytorin ezetimibe /simvastatin Lipid regulation 2004/Merck/SP 2352
Symbicort /DPI/MDI budesonide/formoterol Asthma/COPD 2006/Astra Zeneca 2004
Avandamet Tablets rosiglitane/metformin Diabetes 2002/GSK 1200
Kaletra soft gel lopinavir /ritonavir HIV/AIDS 2000/Abbott 1366
Epzicom abacavir /lamivudine HIV/AIDS 2005/Shire 854
Combivir Tablets lamivudine /zidovudine HIV/AIDS 1997/Shire 665
RECENT FDC APPROVALS
Product Molecules Indications Approval/Company
Ristfor Tablet sitagliptin/metformin Diabetes March 10/Merck(EU)
Duodart dutasteride/tamsulosin BPH March 10/GSK (EU) Tent.
Approved Jan. 10 (USA)
DuoCover/DuoPlavin clopidogre/aspirin ACS/MI March 2010 BMS/SA (EU)
tablet
Azor Tablet amlodipine /olmesartan Hypertension 08/09/Daiichi Sankyo
(USA&EU)
EMBEDA Abuse morphine /naltrexone Pain 09/Alpharma/King Pharma
resistant capsule (USA)
Lipsovir cream acyclovir /hydrocortisone Herpes 09/Medivir/Meda (USA)
Copalia HCT amlodipine /valsartan/ 09/Novartis (EU)
Hypertension
hydrochlorothiazide
09/Takeda (USA)
ACTOplus met XR metformin/pioglitazone Diabetes
Tablets
CONCLUSIONS
• FDCs may offer better treatment through improving
patient compliance
• Greater the noncompliance chance with individual
drugs higher the chance of FDC product success
• New products with patent/market exclusivity.
Overcome formulation challenges for stronger patents
• Growing number of products/pipeline for
cardiovascular, lipid regulation, diabetes, pain,
respiratory diseases and infections
• Majority are based on two molecules, and several 3
mol. FDCs for HIV, Diabetes, Hypertension, etc. and
even 4 mol FDCs for HIV
• Majority are delivered as IR/MR tablets. Also
Inhalation, Topical and Transdermal products
QUESTIONS?
Tugrul Kararli, Ph.D. MBA
Pharmacircle
[Link]
tkararli@[Link]
(760) 436 1199