海德里尼--Hedriny

2003 sales (est.), 34.5 billion; 2002 sales, 31.8 billion; 2001 sales, 26.2 billion;1998 sales, 20 billion;

Glaxo spent nearly $4 billion on R&D in 2002. Glaxo has tried to revitalize its research laboratories by separating them into six Centers for Excellence in Drug Development that compete against one another like individual biotechs.

No. of R&D products (2002): 176; Ranking: 1st; No. of R&D products (2003): 190 (112 of own products); Ranking: 1st;

Anti-Infectives:

Marketed

Augmentin (amoxicillin and clavulanic acid combination): penicillin antibiotic with b-lactamase inhibitor; generic competition

Year	Sales (pounds)	No Structure
2003	872 million (est)
2002	1.8 billion
2001	1.42 billion
2000	1.22 billion
1999	?
1998	964 million

Fortaz/Fortum (ceftazidime): cephalosporin antibiotic; 2001 sales, 201 million;

Agenerase (amprenavir): HIV protease inhibitor; 2001 sales, 50 million;

Combivir/Biovir (lamivudine and zidovudine): RTIs for HIV infections; approved September 1997

Year	Sales (pounds)	No Structure
2002	588 million
2001	606 million
2000	562 million
1999	?
1998	267 million

Zovirax (aciclovir): DNA polymerase for herpes, shingles, chickenpox, cold sores; 2001 sales, 296 million; 1998 sales, 403 million

Ziagen (abacavir): DNA polymerase inhibitor for HIV; 2001 sales, 167 million

Valtrex/Zelitrex (valacyclovir): DNA polymerase inhibitor (nucleoside analog) for genital herpes; 2001 sales, 350 million;

Epivir (lamivudine): nucleoside RTI for hepatitis B infections; 2001 sales, 302 million; 1998 sales, 359 million;

Famvir (famciclovir): DNA polymerase inhibitor for genital herpes and shingles; approved September 1997

Relenza (zanamivir): neuraminidase inhibitor for influenza;

Ceftin/Zinnat (cefuroxime axetil): cephalosporin antibiotic; approved September 1997; 2001 sales, 409 million; 1998 sales, 411 million;

Retrovir (zidovudine): nucleoside RTI for HIV; 2001 sales, 55 million;

In Development

tRNA synthetase inhibitor program (antibacterial) (2002); HCV NS3/4A protease program (2003); FabI/FabK inhibitor program (2003); HCV NS5B inhibitor program (2002);HCV immunomodulator program (2002);

Fosamprenavir: HIV protease inhibitor; prodrug of amprenavir; Phase II/Phase III (2003); possible advantage with once a day dosing;

43908: HIV protease inhibitor; Phase III (2003)

640385: HIV protease inhibitor; Phase I (2002)

695634: NNRTI for HIV; Phase I (2002)

ONO-4128: CCR5 antagonist for HIV; from Ono Pharmaceuticals; Phase I (2003)

810781: HIV integrase inhibitor; Phase II (2002)

MIV-210: nucleoside RTI for HIV; prodrug of dideoxyguanidine; from Medivir; Phase I (2003)

Factive (gemifloxacin mesylate): DNA gyrase and topoisomerase IV inhibitor; quinolone antibiotic; Phase III (2003)

Hepatitis E Vaccine: Phase II (2003)

Hepatitis B Vaccine: Phase III (2003)

Cardiovascular:

Marketed

Coreg (carvedilol): a,b-blocker for congestive heart failure; 2001 sales, 251 million;

In Development

a-1 adrenergic receptor antagonist program (2002);

Ariflo (cilomilast): PDE-IV inhibitor for chronic obstructive pulmonary disease; rejected by FDA for that indication (2003); Phase II (2003) for asthma

Piboserod HCl: 5-HT4 receptor antagonist for gastric esophageal reflux disease and atrial fibrillation; Phase I (2003); Phase III in 1997 for irritable bowel

GW-473178: thrombin inhibitor for thrombosis; iv formulation; Phase I (2003)

SB-424323: indirect thrombin inhibitor for thrombosis; oral formulation; Phase II (2003)

GW-501516: PPAR d agonist for dyslipidemia; with Ligand; Phase I (2003)

GW-590735: PPAR agonist for dyslipidemia; Phase I (2003)

GW-249417: anti-Factor IX monoclonal antibody for stroke

CNS:

Marketed

Paxil (paroxetine): selective serotonin reuptake inhibitor for generalized anxiety disorder; anxiety, and depression; Paxil litigation with Apotex starts Feb 5, 2003; Generic competition; may be addictive; removed labeling claim that it was not addictive in Britain (2003);British drug regulators warned that Paxil should not be used to treat depression in people under 18 (6/03);

Year	Sales (pounds)
2003	1.96 billion (est)
2002	3.1 billion
2001	1.86 billion
2000	1.55 billion
1999	?
1998	1.06 billion

Imigran/Imitrex (sumatriptan): 5-HT1 agonist for migraines; approved August 1997

Year	Sales (pounds)
2002	798 million
2001	758 million
2000	?
1999	?
1998	698 million

Wellbutrin (bupropion HCl): noradrenaline/dopamine reuptake inhibitor for ADHD; Phase III (2003)

Year	Sales (pounds)
2003	864 million (est)
2002	882 million
2001	647 million
2000	?
1999	?
1998	307 million

Naramig/Amerge (naratriptan): 5-HT1 agonist for migraines; 2001 sales, 91 million;

In Development

5-HT7 receptor antagonist program (2002);

Talnetant: tachykinin (NK3) antagonist for schizophrenia; Phase II (2003)

Alvimopan: mu opioid antagonist for post-operative ileus; Phase III (2003)

Caraberset: benzopyran for migraines and epilepsy; Phase II (2003)

Manifaxine (GW-320659): noradrenergic and dopaminergic reuptake inhibitor for ADHD; Phase II (2003)

SB-271046: 5-HT6 antagonist for schizophrenia and Alzheimer’s disease; Phase I (12/2002)

SB-424323: for stroke; Phase II (2003)

SB-683698: dual a-4 integrin (VLA4) antagonist for inflammatory bowel disease and multiple sclerosis; Phase I (12/2002)

Vilazodone (EMD-68843; SB-659746): selective serotonin reuptake inhibitor/5-HT1A partial antagonist for depression; Phase IIb (2003); dropped 5/2003 due to lack of efficacy

SB-679769: NK1 antagonist for depression and anxiety; Phase II (2002)

SB-597599: NK1 antagonist for depression and anxiety; Phase I (2002)

353162: noradrenaline/dopamine reuptake inhibitor for depression and bipolar disorder; Phase I (2003)

723620: corticotropin releasing factor antagonist for anxiety and depression; Phase I (2002)

Diabetes/Obesity:

Marketed

Avandia (rosiglitazone): PPARg agonist for type 2 diabetes

Year	Sales (pounds)
2003	904 million (est)
2002	809 million
2001	707 million
2000	462 million
1999	?
1998	-

In Development

GI-181771: CCK-A antagonist for obesity; Phase II (2003); non-insulin dependent diabetes mellitus, Phase I (2003)

GW-427353: b3 adrenergic receptor agonist for non-insulin dependent diabetes mellitus; Phase I (12/2002)

GW-677954: PPAR agonist for non-insulin dependent diabetes mellitus; Phase I (2003)

876167: 5-HT2C agonist for obesity;

Gastrointestinal

In Development

Lotronex (alosetron HCl): 5-HT3 receptor antagonist for irritable bowel; Phase III (2003)

Talnetant: tachykinin (NK3) antagonist for irritable bowel; Phase I (2003)

Alvimopan: peripheral mu opioid antagonist for irritable bowel; Phase II (2003)

SB-723620: corticotropin releasing factor antagonist for irritable bowel; Phase I (2003)

SB-281832: for inflammatory bowel disease; Phase I (2003)

SB-683698: dual a-4 integrin (VLA4) antagonist for inflammatory bowel disease and multiple sclerosis; Phase I (2003)

Repifermin (keratinocyte growth factor-2 / KGF): for inflammatory bowel disease; Phase II (2003)

Piboserod HCl: 5-HT4 receptor antagonist for gastric esophageal reflux disease and atrial fibrillation; Phase I (2003); Phase III in 1997 for irritable bowel

SB-641257: for gastric esophageal reflux disease; Phase I (2003)

Inflammation/Immunology:

Marketed

Advair/Seretide (salmeterol): b2 agonist for asthma

Year	Sales (pounds)
2003	2.06 billion (est)
2002	2.4 billion
2001	850 million
2000	208 million

Flixonase/Flonase (fluticasone propionate): inhaled corticosteroid for asthma

Year	Sales (pounds)	No Structure
2002	534 million
2001	504 million
2000	?
1999	?
1998	273 million

Flixotide/Flovent (fluticasone propionate): inhaled corticosteroid for asthma

Year	Sales (pounds)	No Structure
2002	783 million
2001	915 million
2000	?
1999	?
1998	498 million

In Development

PLA2 program (2002); p38a MAP kinase inhibitor program (2002);

406381: COX-2 inhibitor for inflammation and pain;

SB-480848: lipoprotein-associated phospholipase A2 inhibitor; Phase I (2003)

SB-659032: lipoprotein-associated phospholipase A2 inhibitor; Phase I (2003)

Men's health:

Marketed

Avodart (dutasteride): 5a-reductase inhibitor; approved and on market for benign prostatic hyperplasia; male hair loss; approved November 2001;

Levitra (vardenafil): PDE-5 inhibitor for erectile dysfunction; analysts predict that it could generate annual sales of 1 billion by 2007; approved 8/03;

Oncology:

Marketed

Zofran (ondansetron): 5-HT3 receptor antagonist for prevention of postoperative nausea and vomiting (PONV), cancer chemotherapy-induced nausea and vomiting (CINV), and radiotherapy-induced nausea and vomiting (RINV)

Year	Sales (pounds)
2003	728 million (est)
2002	708 million
2001	601 million
2000	?
1999	?
1998	389 million

In Development

Erb-2/EGFR tyrosine kinase inhibitor program (2002);

Bexxar: radioimmunotherapy for non-Hodgkins lymphoma; to be launched over next two years (2003); FDA has decided to extend its review for up to 3 months;

GW-572016: EGF receptor and HER2 tyrosine kinase inhibitor for solid tumors; Phase I (2003)

572016: Erb-2 and EGF receptor tyrosine kinase inhibitor for breast and colorectal cancer; Phase II (2002)

786034: VEGF receptor tyrosine kinase inhibitor for solid tumors; Phase I (2002)

Hycamtin (topotecan): topoisomerase I inhibitor for ovarian and non-small cell lung cancers; Phase II (2002)

Navelbine (vinorelbine): for non-small cell lung cancer;