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APPENDIX F Approval Dates for Existing and Prospects for Development of New Antituberculosis Drugs and Vaccines
Please refer to the page image for an unflawed representation of this content. TABLE F-1 Approval Dates for Antituberculosis Drugs and Vaccines Drug
FDA Approval Date or Year of First USPHS Published Trial (*)
Isoniazid
1953*
Rifamycins
rifampin
1974*
rifabutin
12/23/1992
rifapentine
6/22/1998
Pyrazinamide
1959*
Ethambutol
1968*
Streptomycin
1947*
Para-aminosalicylic acid (PAS)
1950*
Ethionamide
1968*
Cycloserine
1968*
Capreomycin
1956*
Kanamycin
Discovered early 1950s; not studied in USPHS trial
Thiacetazone (not available in United States)
—
Fluoroquinolones
ciprofloxacin
12/26/1990
ofloxacin
12/28/1990
levofloxacin
12/20/1996
Amikacin
Before 1/01/1982
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Please refer to the page image for an unflawed representation of this content. TABLE F-2 Pharmaceutical Companies: Current (1999) Prospects for Development of New Antituberculosis Drugs and Vaccines New Antimicrobials Available in:
Company
2 Years
5 Years
8 Years
Vaccines
Abbott Laboratories
0
0
0
0
American Home Products (Lederle/Wyeth-Ayerst)
0
0
0
0
Astro-Zeneca Pharmaceuticals
0
0
0
0
Bristol-Myers Squibb
0
0
0
0
Dupont Pharmaceuticals
0
?oxazolidinones
?oxazolidinones
0
Eli Lilly and Company
0
0
0
0
Glaxo-Wellcome
0
0
?
Working on vaccines
DNA
Whole attenuated live organism
Therapeutic vaccine
Hoechst Marion Roussel
0
0
0
0
Rifapentine approved by FDA in 1998
Janssen Pharmaceuticals
0 0
0 0
Merck and Company
0 0
0
Very exploratory; have rights to a DNA vaccine in the public domain. Would also be interested in a subunit vaccine
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Novartis Pharmaceuticals
0
0
0
0
Ortho-McNeil Johnson & Johnson
0
Sending some candidate drugs out for in vitro testing; marketing experts not enthusiastic
0
Parke-Davis
0
0
0
0
Pfizer, Inc.
0
0
0
0
Pharmacia/Upjohn
0
?oxazolidinones
?oxazolidinones
0
Rhone-Poulene Rorer
0 0
0 0
Roche Pharmaceuticals
Had some preliminary work on IL-12 but gave up when in animals it increased CFU in lung
Had some preliminary work on IL-12 but gave up when in animals it increased CFU in lung
Had some preliminary work on IL-12 but gave up when in animals it increased CFU in lung
Had some preliminary work on IL-12 but gave up when in up when in animals it increased CFU in lung
Schering-Plough Corp.
0
0
0
0
G.D. Searle-Monsanto Co.
0
0
0
0
Smith Kline Beecham Pharmaceuticals
0
0
0
0
Warners Chilcott Laboratories
0
0
0
0
Warner Lambert Co.
0
0
0
0
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Please refer to the page image for an unflawed representation of this content. TABLE F-3 Biotechnology Companies: Current (1999) Prospects for Development of New Antituberculosis Drugs and Vaccines New Antimicrobials Available in:
Company
2 Years
5 Years
8 Years
Vaccines
Biogen
0
0
0
0
Corixa Corp.
0
0
0
Vaccines are their approach, not antimicrobials
Collaborating with Smith Kline Beecham
Working on vaccine for 3 years
Have developed a vaccine utilizing 3–5 protein antigens made by incorporating genes for these proteins (a synthetic gene) with effective epitopes (multiple) in one recombinant protein
Efficacy already shown in a rodent model
Safety already shown in monkeys
Clinical trials (Brazil and in another country) phase I/II in approximately 1 year
Genetech
0
0
0
0
Genetics Institute
IL-12 plus 3 drugs—study vs. TB in Gambia (currently under way)
IL-12 plus 3 drugs—study vs. MA-I in patients with genetic defects in interferon receptor
IL-12 plus 3 drugs—study in treatment of M. tuberculosis or MA-I in HIV-infected patients, an ACTG study
?
?
?
Pathogenesis Corp.
Rifamycin analog (Rifalizyl) with longer half-life cross- resistant with rifampin so not pursuing any longer
PA 824 (a nitroimidizopyrene) under development—active as a drug vs. drug-resistant M. tuberculosis (acts by inhibiting glycolipid cell wall synthesis, but at a different step than is inhibited by ethambutol). Presented as a prodrug that is activated in host (as in the case of INH).
0
0
0
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1) Activity: mole for mole as active as INH
2) Orally active
3) Bactericidal
4) Active vs. nongrowing organisms (e.g., M. tuberculosis cultured under anaerobic conditions)
5) Now in initial stages of testing
Ribozyme Pharmaceuticals
0
0
0
0
Sequella Corp.
Ethambutol analogs (3 candidates)
Clinical testing probably
Clinical testing probably
Vaccine: Has license for new experimental vaccine (Nature 400[6741]:269; 1999)
Shikemic acid pathway
0
0
(inhibitor)
New diagnostic being studied: A patch test that may be positive in patients with active disease but not in individuals with prior infection
Representative terms from entire chapter:
antituberculosis drugs
