美国2001年开发中的抗爱滋病新药

As the war against AIDS enters its third decade, phar-maceutical companies are continuing to research newweapons to thwart this persistent and deadly enemy. The 98 drugs and vaccines currently in the pharmaceutical pipeline will augment the 68 medicines already approved for the treatment of AIDS and AIDS-related conditions. In the past year alone, four new medicines were added to this arsenal: a medicine for an AIDS-related fungal infection; a medicine for AIDS-related cytomegalovirus (CMV) retinitis; a medicine that combines three antiretroviral drugs in one tablet, and the first in a new class of medicines called nucleotides which, in clinical trials, proved effective in patients who had developed resistance to other drugs. In 1987, just four years after the virus that causes AIDS was identified, a pharmaceutical company introduced the first medicine approved to treat this disease. In the years that followed, dozens more medicines were invented, both to fight the virus and to treat the opportunistic infections that attack the weakened immune systems of AIDS patients. There is strong evidence that these medicines are working to prolong the lives of AIDS patients and to improve the quality of their lives. New medicines have drastically reduced the incidence of mother-to-child transmission of AIDS, and, since the mid-1990s, when the first protease inhibitors were launched and combination drug therapy was introduced, the U.S. death rate from AIDS has dropped about 80 percent. New treatments have proved not only effective, but cost-effective. According to a study published in March in The New England Journal of Medicine, combination drug therapy not only saves lives and improves the quality of life—it also saves health care dollars compared to the inferior therapy it replaces. The study found that after the advent of combination drug therapy, hospitalization costs fell by 43 percent while spending on pharmaceuticals rose 33 percent. Despite these inroads against AIDS, it remains a formi- dable and wily foe. Today, the Centers for Disease Control estimates that 800,000 to 900,000 people in the United States are infected with the virus and more than 320,000 are living with AIDS. And the virus itself has the ability to con- stantly mutate—or change—outwitting and resisting drugs. “Drug resistance with this virus is a big issue,” says Dr. Michael Rogers, head of HIV Clinical Development at GlaxoSmithKline. “We are constantly looking for new drugs that can defeat these mutated viruses.” Some of the medicines in the pipeline attempt to address the problem of drug resistance by working in different ways from existing medicines. For example, there are several fusion inhibitors, which work by blocking the virus from fusing with healthy cells. Several companies are working on vaccines—which would be especially helpful in the developing world where most of the 35 million adults and 1.3 million children afflicted with HIV/AIDS worldwide live (See page 15). “Everything in science suggests that a vaccine is possible,” says Seth Berkley, CEO of the International AIDS Vaccine Initiative. One promising candidate combines, in a disabled cold virus, DNA snippets from the AIDS virus with a protein that boosts the immune response. The aim is not to prevent infection but to limit the damage the virus can cause. Companies are also working on ways to halt the progres- sion from HIV infection to AIDS. For example, one medicine in development is an immune-regulating hormone designed to induce the immune system to mount a defense that will keep the virus in check and slow or prevent the progression to AIDS. Instead of attacking the virus directly, the medicine aims to increase the percentage of patients who, though infected, avoid the symptoms of AIDS. In all, 68 companies are working on AIDS medicines, some in conjunction with the National Institutes of Health. All of the medicines are either in clinical trials or awaiting approval by the Food and Drug Administration. Alan F. Holmer President and CEO PhRMA 2001 AIDS N E W M E D I C I N E S I N D E V E L O P M E N T F O R Survey P R E S E N T E D B Y A M E R I C A ’ S P H A R M A C E U T I C A L C O M P A N I E S Drug Companies Keep Up AIDS Research Momentum With 98 Medicines in Development Vaccines Immunomodulators Antivirals Antifungals Anti-Infectives 6 7 38 8 14 Anticancers 15 14Others 2001 MEDICINES IN DEVELOPMENT FOR AIDS* *Some medicines are l is ted in more than one category. New Medicines in Development for AIDS A N T I C A N C E R S Product Name Company Indication Development Status* A-007 Dekk-Tec AIDS-related Kaposi’s sarcoma Phase I New Orleans, LA ATRAGEN® Antigenics non-Hodgkin’s lymphoma Phase II tretinoin New York, NY (212) 332-4774 Beta LT LifeTime Pharmaceuticals B-cell lymphoma, multiple Phase I/II beta-alethine College Park, MD myeloma (301) 314-1480 (Orphan Drug) BMS 275291 National Cancer Institute AIDS-related Kaposi’s sarcoma Phase I/II (MMPI) Bethesda, MD N C I T R I A L Bristol-Myers Squibb (800) 422-6237 Princeton, NJ DaunoXome® Gilead Sciences non-Hodgkin’s lymphoma and Phase II daunorubicin Foster City, CA certain leukemias (650) 574-3000 citrate liposome injection interleukin-12 National Cancer Institute AIDS-related Kaposi’s sarcoma Phase II Bethesda, MD N C I T R I A L (800) 422-6237 Metastat™ CollaGenex Pharmaceuticals HIV-related Kaposi’s sarcoma Phase II 4-dedimethyl- Newtown, PA (215) 579-7388 sancycline Multikine CEL-SCI cervical cancer in HIV and Phase I leukocyte Vienna, VA human papillomavirus (HPV) (703) 506-9460 interleukin co-infected women injection (see also immunomodulators) Onco TCS Inex Pharmaceuticals non-Hodgkin’s lymphoma Phase II/III Burnaby, British Columbia (604) 419-3200 ONTAK® Seragen/Ligand non-Hodgkin’s lymphoma Phase II denileukin Pharmaceuticals (858) 550-7500 diftitox San Diego, CA Panretin® Capsules Ligand Pharmaceuticals AIDS-related Kaposi’s sarcoma Phase II alitretinoin, San Diego, CA (858) 550-7500 9-cis-retinoic acid Paxene™ IVAX Pharmaceuticals AIDS-related Kaposi’s sarcoma Phase III paclitaxel Miami, FL (305) 575-6000 Proleukin® National Cancer Institute AIDS-related lymphoma and Phase II aldesleukin, Bethesda, MD non-Hodgkin’s lymphoma N C I T R I A L interleukin-2 (see also immunomodulators) (800) 422-6237 (IL-2) Rituxan™ National Cancer Institute HIV-related non-Hodgkin’s Phase II rituximab Bethesda, MD lymphoma, HIV-associated N C I T R I A L IDEC Pharmaceuticals lymphomas (800) 422-6237 San Diego, CA 2 N E W M E D I C I N E S I N D E V E L O P M E N T F O R AIDS 2001 * For more information about a specific medicine in this report, please call the telephone number listed. A N T I C A N C E R S Product Name Company Indication Development Status* Taxol® National Cancer Institute AIDS-related Kaposi’s sarcoma Phase II/III paclitaxel Bethesda, MD N C I T R I A L Bristol-Myers Squibb (800) 422-6237 Princeton, NJ A N T I F U N G A L S Product Name Company Indication Development Status AmBisome® Fujisawa Healthcare histoplasmosis Phase III liposomal Deerfield, IL (800) 727-7003 amphotericin B Gilead Sciences for injection Foster City, CA FK463 Fujisawa Healthcare esophageal candidiasis in AIDS Phase III Deerfield, IL patients (800) 727-7003 Nyotran® Antigenics candidemia, systemic Phase III completed liposomal nystatin New York, NY fungal infections, cryptococcal (212) 332-4774 meningitis, aspergillosis Oramed® Biosyn HIV-related oral candidiasis Phase II C31G oral rinse Philadelphia, PA (215) 387-5338 posaconazole Schering-Plough opportunistic fungal infections Phase III (oral triazole) Kenilworth, NJ (908) 298-4000 Vfend® Pfizer serious fungal infections application submitted voriconazole New York, NY (860) 732-6058 A N T I - I N F E C T I V E S Product Name Company Indication Development Status dapsone Jacobus Pharmaceutical Pneumocystis carinii pneumonia Phase III Princeton, NJ (PCP) prophylaxis (609) 921-7447 dapsone and Jacobus Pharmaceutical PCP and toxoplasmosis Phase III pyrimethamine Princeton, NJ prophylaxis (609) 921-7447 and folinic acid dapsone with Jacobus Pharmaceutical PCP treatment Phase III trimethoprim Princeton, NJ (609) 921-7447 DB 289 Immtech International PCP treatment Phase I Vernon Hills, IL DiffGAM Immucell treatment and prevention of Phase II hyperimmune Portland, ME diarrhea caused by (800) 466-8235 globulin (bovine Clostridium difficile milk), oral (enterocolonic) SYNSORB-Cd® SYNSORB Biotech treatment of recurrent Phase III Calgary, Alberta Clostridium difficile infections (403) 283-5900 (AIDS-related diarrhea) Ushercell Polydex Pharmaceuticals prevention of AIDS and other Phase I Toronto, Ontario sexually transmitted diseases (416) 755-2231 3N E W M E D I C I N E S I N D E V E L O P M E N T F O R AIDS 2001 A N T I V I R A L S Product Name Company Indication Development Status adefovir dipivoxil Gilead Sciences chronic hepatitis B virus Phase III Foster City, CA (650) 574-3000 Alferon N Interferon Sciences HIV infection Phase III Injection® New Brunswick, NJ (888) 728-4372 interferon alfa-n3 -------------------------------------------------------------------------------------- HIV & hepatitis C co-infection Phase II (see also immunomodulators) (888) 728-4372 amdoxovir Abbott Laboratories HIV disease treatment Phase II (DAPD) Abbott Park, IL (919) 493-5980 (purine nucleoside Triangle Pharmaceuticals analogue) Durham, NC Ancer 20 Injection Zeria USA HIV infection Phase I Scarsdale, NY Anticort™ Samaritan Pharmaceuticals HIV infection Phase II completed procaine HCl Las Vegas, NV (see also other) (702) 735-7001 atazanavir Bristol-Myers Squibb first-line combination therapy for Phase III BMS 232632 Princeton, NJ the treatment of acute and chronic (212) 546-4000 (protease inhibitor) HIV infection Aztec® Verex Laboratories HIV infection/AIDS Phase III completed zidovudine Englewood, CO (controlled release) BMS 561390 Bristol-Myers Squibb HIV infection Phase I/II (non-nucleoside Princeton, NJ (212) 546-4000 reverse transcriptase inhibitor) calanolide A Sarawak MediChem HIV infection Phase II (non-nucleoside Pharmaceuticals (630) 739-6744 reverse transcriptase Lemont, IL inhibitor) capravirine Agouron Pharmaceuticals, HIV infection/AIDS Phase II AG 1549 a Pfizer Company (860) 732-6058 (non-nucleoside La Jolla, CA reverse Pfizer transcriptase New York, NY inhibitor) clevudine Abbott Laboratories hepatitis B treatment Phase II (pyrimidine nucleo- Abbott Park, IL (919) 493-5980 side analogue) Triangle Pharmaceuticals Durham, NC Coactinon® Abbott Laboratories HIV disease treatment Phase III emivirine Abbott Park, IL (919) 493-5980 (non-nucleoside Triangle Pharmaceuticals reverse transcriptase Durham, NC inhibitor) Coviracil® Abbott Laboratories HIV disease treatment Phase III emtricitabine Abbott Park, IL (919) 493-5980 (nucleoside Triangle Pharmaceuticals -------------------------------------------------------------------------------------- analogue) Durham, NC hepatitis B treatment Phase III (919) 493-5980 4 N E W M E D I C I N E S I N D E V E L O P M E N T F O R AIDS 2001 A N T I V I R A L S Product Name Company Indication Development Status entecavir Bristol-Myers Squibb HIV & hepatitis B co-infection Phase II (BMS 200475) Princeton, NJ (212) 546-4000 Epivir® GlaxoSmithKline HIV infection application submitted lamivudine Philadelphia, PA (888) 825-5249 (once-daily dosing) Rsch. Triangle Park, NC Epivir® GlaxoSmithKline HIV infection Phase III lamivudine Philadelphia, PA (888) 825-5249 Ziagen® Rsch. Triangle Park, NC abacavir (combination tablet) GEM®92 Hybridon HIV infection Phase I Cambridge, MA (617) 679-5500 low-dose oral Atrix Laboratories treatment of oral warts Phase I interferon-alpha Fort Collins, CO (970) 482-5868 ME-609 cream Medivir recurrent labial herpes Phase II completed Huddinge, Sweden (cold sores) 46-8-608-3100 MIV-150 Chiron HIV infection Phase I (non-nucleoside Emeryville, CA 46-8-608-3100 reverse transcriptase Medivir inhibitor) Huddinge, Sweden MIV-210 Medivir hepatitis B virus Phase I Huddinge, Sweden 46-8-608-3100 MIV-310 Medivir multi-resistant HIV infection Phase II Huddinge, Sweden 46-8-608-3100 mozenavir Triangle Pharmaceuticals HIV disease treatment Phase II (second generation Durham, NC (919) 493-5980 protease inhibitor) PRO 542 Progenics Pharmaceuticals HIV infection Phase II Tarrytown, NY (914) 789-2800 Genzyme Transgenics Framingham, MA PRO 2000 Interneuron Pharmaceuticals prevention of HIV infection Phase II (topical gel) Lexington, MA transmission (781) 861-8444 protease inhibitor Bristol-Myers Squibb HIV infection Phase I Princeton, NJ (212) 546-4000 S-1360 GlaxoSmithKline HIV infection/AIDS Phase II (HIV integrase Philadelphia, PA (888) 825-5249 inhibitor) Rsch. Triangle Park, NC (973) 966-6900 Shionogi USA Florham Park, NJ SPD 754 Shire Pharmaceutical AIDS Phase I Development (240) 453-6400 Rockville, MD SPD 756 Shire Pharmaceutical AIDS Phase I Development (240) 453-6400 Rockville, MD 5N E W M E D I C I N E S I N D E V E L O P M E N T F O R AIDS 2001 A N T I V I R A L S Product Name Company Indication Development Status Sustiva® Bristol-Myers Squibb HIV infection application submitted efavirenz Princeton, NJ (212) 546-4000 (once-daily) T-20 Roche HIV-1 infection Phase III (fusion inhibitor) Nutley, NJ (973) 235-5000 (R029-9800) Trimeris Durham, NC T-1249 Roche HIV-1 infection Phase I/II (fusion inhibitor) Nutley, NJ (973) 235-5000 (R029-9801) Trimeris Durham, NC tipranavir Boehringer Ingelheim AIDS of HIV-1 type Phase II (protease inhibitor) Pharmaceuticals (203) 798-9988 Ridgefield, CT TMC120 Tibotec HIV infection Phase II (non-nucleoside Rockville, MD (301) 519-1919 reverse transcriptase inhibitor) Valtrex™ GlaxoSmithKline cold sores Phase III valacyclovir Philadelphia, PA (888) 825-5249 Rsch. Triangle Park, NC -------------------------------------------------------------------------------------- herpes simplex virus (HSV) Phase III suppression in immuno- (888) 825-5249 compromised patients -------------------------------------------------------------------------------------- prevention of HSV transmission Phase III (888) 825-5249 Veldona® Amarillo Biosciences human papillomavirus- Phase II interferon-alpha Amarillo, TX induced oral warts related to (806) 376-1741 lozenges HIV infection (Orphan Drug) VX-175 GlaxoSmithKline HIV infection Phase III (GW433908) Philadelphia, PA (888) 825-5249 Rsch. Triangle Park, NC Vertex Pharmaceuticals Cambridge, MA Zerit® Bristol-Myers Squibb HIV infection Phase III stavudine Princeton, NJ (212) 546-4000 (extended-release formulation) 6 N E W M E D I C I N E S I N D E V E L O P M E N T F O R AIDS 2001 I M M U N O M O D U L A T O R S Product Name Company Indication Development Status Alferon N Interferon Sciences HIV infection Phase III Injection® New Brunswick, NJ (888) 728-4372 interferon alfa-n3 -------------------------------------------------------------------------------------- HIV & hepatitis C co-infection Phase II (see also antivirals) (888) 728-4372 Ampligen® Hemispherx Biopharma HIV infection/AIDS Phase II Philadelphia, PA (215) 988-0080 CBP-1011 InKine Pharmaceutical idiopathic thrombocytopenic Phase III Blue Bell, PA purpura (215) 283-6850 HE2000 Hollis-Eden HIV infection/AIDS Phase I/II Pharmaceuticals (858) 587-9333 San Diego, CA HspE7 StressGen Biotechnologies anal dysplasia in HIV-infected Phase III Victoria, British Columbia individuals (800) 661-4978 -------------------------------------------------------------------------------------- genital warts Phase II (800) 661-4978 Multikine CEL-SCI cervical dysplasia in HIV and Phase I leukocyte Vienna, VA human papillomavirus (HPV) (703) 506-9460 interleukin co-infected women injection (see also anticancers) Proleukin® Chiron HIV infection Phase III aldesleukin, Emeryville, CA (see also anticancers) (510) 655-8730 interleukin-2 (IL-2) WF10 OXO Chemie late stage HIV disease Phase III South San Francisco, CA V A C C I N E S Product Name Company Indication Development Status AIDS subunit ID Vaccine treatment of AIDS Phase II vaccine Bothell, WA TheraGuide New York, NY AIDS vaccine United Biomedical HIV infection Phase I Hauppauge, NY AIDSVAX® VaxGen HIV infection prophylaxis Phase III Brisbane, CA (650) 624-1000 ALVAC™ Aventis Pasteur HIV infection prophylaxis and Phase II (vCP1452) Swiftwater, PA immunotherapy (570) 839-4267 ALVAC™ Aventis Pasteur HIV infection prophylaxis and Phase II (vCP1521) Swiftwater, PA immunotherapy (570) 839-4267 cytomegalovirus Aviron cytomegalovirus (CMV) Phase I (CMV) vaccine Mountain View, CA (650) 919-6500 7N E W M E D I C I N E S I N D E V E L O P M E N T F O R AIDS 2001 V A C C I N E S Product Name Company Indication Development Status Genevax-HIV® Wyeth-Lederle Vaccines HIV infection prophylaxis Phase I APL-400-003 Philadelphia, PA and treatment (610) 902-1200 (end/rev) facilitated DNA-based vaccine Genevax-HIV® Wyeth-Lederle Vaccines HIV infection prophylaxis Phase I APL-400-047 Philadelphia, PA and treatment (610) 902-1200 (gag/pol) facilitated DNA-based vaccine HGP-30W CEL-SCI HIV infection prophylaxis Phase II HIV-1 vaccine Vienna, VA (703) 506-9460 HIV peptide National Cancer Institute early HIV infection Phase I AIDS vaccine Bethesda, MD N C I T R I A L (800) 422-6237 HIV recombinant GlaxoSmithKline HIV prophylaxis Phase I vaccine Philadelphia, PA (888) 825-5249 Rsch. Triangle Park, NC HIV vaccine Merck prevention and treatment of HIV Phase I Whitehouse Station, NJ infection/AIDS (800) 672-6372 Simplirix GlaxoSmithKline genital herpes prophylaxis Phase II recombinant Philadelphia, PA (888) 825-5249 vaccine Rsch. Triangle Park, NC TBC-3B Therion Biologics AIDS Phase I recombinant Cambridge, MA (617) 876-7779 vaccine O T H E R S Product Name Company Indication Development Status Anticort™ Samaritan Pharmaceuticals AIDS-associated dementia Phase II completed procaine HCl Las Vegas, NV (see also antivirals) (702) 735-7001 CCR5 receptor Schering-Plough HIV infection in clinical trials antagonist Kenilworth, NJ (908) 298-4000 Cytolin® Amerimmune HIV infection Phase I/II Pharmaceuticals (714) 734-5000 Irvine, CA DPI3290 Ardent Pharmaceuticals severe pain Phase II Durham, NC (919) 806-1806 HGTV43 Enzo Biochem HIV infection Phase I (gene therapy) Farmingdale, NY HIV therapeutic United Biomedical block progression from Phase I Hauppauge, NY HIV infection to AIDS Morphelan™ ROER Elan Pharmaceuticals moderate to severe pain application submitted morphine sulfate South San Francisco, CA (858) 550-7500 rapid onset Ligand Pharmaceuticals extended release San Diego, CA 8 N E W M E D I C I N E S I N D E V E L O P M E N T F O R AIDS 2001 O T H E R S Product Name Company Indication Development Status NEUPOGEN® Amgen treatment of neutropenia application submitted filgrastim Thousand Oaks, CA in HIV-infected patients (805) 447-1000 (G-CSF) Savvy® Biosyn prevention of HIV transmission and Phase I/II C31G vaginal gel Philadelphia, PA other sexually transmitted diseases (215) 387-5338 (vaginal microbicide) Serostim™ Serono abnormal fat accumulation in Phase II somatropin (rDNA Norwell, MA HIV-related lipodystrophy syndrome (800) 283-8088 origin) for injection (Orphan Drug) T902611 (T611) Tularik treatment of cytomegalovirus (CMV) Phase I South San Francisco, CA (650) 825-7000 Thalomid™ Celgene AIDS wasting Phase III completed thalidomide Warren, NJ (800) 890-4619 -------------------------------------------------------------------------------------- aphthous ulcers in HIV positive Phase III patients (800) 890-4619 Zadaxin® SciClone Pharmaceuticals HIV infection/AIDS Phase II thymalfasin San Mateo, CA (650) 358-3456 ziconotide Elan Pharmaceuticals management of severe pain application submitted South San Francisco, CA (including HIV-infected patients) (650)