美国2003年开发中的HIV-爱滋病新药

To combat the one of the world’s most devastatingdiseases, pharmaceutical and biotechnologyresearchers are testing 83 medicines for HIV/AIDS and related conditions, intensifying their efforts and achieving steady progress in the development of vaccines. The medicines in the pipeline will add to the 80 that have been approved since the virus that causes AIDS was first identified just 20 years ago. In what has been called “a silent revolution in AIDS vaccine research,” 15 new vaccines are in development and, according to the R&D database, Pharmaprojects, 62 projects were being evaluated earlier this year. Vaccine research is considered crucial to control the AIDS pan- demic. In September, it was announced that the first global human tests of an experimental AIDS vaccine had begun in 18 cities in North America, South America, the Caribbean, Southern Africa, and Southeast Asia. “I’m certainly more optimistic than just a couple of years ago (about vaccine research),” said Dr. Robert Gallo, who discovered the virus that causes AIDS and is among those working to develop a vaccine. “We can see the light at the end of the tunnel.” AIDS has killed 28 million people and infected an estimated 42 million people worldwide, 70 percent of whom live in sub-Saharan Africa, where the pharmaceu- tical industry is making special efforts to counter the disease (see page 14). As many as 950,000 U.S. residents are estimated to be living with HIV infection, though the increased use of new medicines has helped to substan- tially reduce the death rate from AIDS in this country in recent years. By 2010, it’s estimated that 45 million new people could be infected with the HIV virus—unless there’s a dramatic breakthrough. “A safe and effective HIV vaccine is critical to the control of HIV globally,” says Dr. Anthony Fauci, Director of the National Institute of Allergy and Infectious Disease. In addition to the 15 vaccines, the medicines in devel- opment, which are either in human clinical trials or are at the Food and Drug Administration awaiting approval, include 33 antivirals, 7 anti-infectives, 6 anti-cancer treat- ments, 9 immunomodulators, 4 antifungals, and 13 other types of drugs. Of the medicines and vaccines in development, one vaccine is designed to induce different types of immune response, enhancing the overall immune response. The first dose primes the body to induce cellular immunity. The booster dose, consisting of genetically engineered HIV subunits, induces neutralizing antibodies. Another vaccine candidate is made from a noninfectious copy of a protein from the surface of the AIDS virus. The vaccine is designed to induce an immune response through the production of antibodies that will prevent the invading virus from attaching to a patient’s T-cells. Examples of other AIDS medicines in the pipeline include: • A medicine that tries to block the integrase enzyme. Existing drugs block one of two enzymes the HIV virus need to reproduce, the reverse transcriptase and protease enzymes. But HIV also needs an enzyme known as integrase to make more copies of itself. This potential new medicine would be the first to block that enzyme. • An antisense gene therapy that uses two novel tech- nologies to boost immune responsiveness against HIV. One involves the insertion of a new type of genetic material into blood cells to inhibit the growth of the virus. The second involves inserting new genes into target cells and integrating the gene into the chromo- some of the cell. The cells containing the new genes are then transferred to the patient. While HIV/AIDS remains a formidable foe and world- wide scourge, pharmaceutical and biotechnology companies are meeting the challenge by continuing their all-out efforts to develop novel and more effective therapies and vaccines to contain the disease. They fully understand that patients all over the world are depending on them. Alan F. Holmer President and CEO PhRMA 2003 HIV/AIDS 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 Researchers Are Testing 83 Medicines for HIV/AIDS; Progress Being Made in Developing Vaccines Vaccines Immunomodulators Antivirals Antifungals Anti-Infectives 4 7 33 9 15 Anticancers 6 13Others 2003 MEDICINES IN DEVELOPMENT FOR AIDS* *Some medicines are l is ted in more than one category. Medicines in Development for HIV/AIDS A N T I C A N C E R S Product Name Sponsor Indication Development Status* A-007 Dekk-Tec AIDS-related Kaposi’s sarcoma Phase I New Orleans, LA Avastin™ National Cancer Institute AIDS-related Kaposi’s sarcoma Phase II bevacizumab Bethesda, MD N C I T R I A L Genentech (800) 4-CANCER South San Francisco, CA BMS 275291 Bristol-Myers Squibb AIDS-related Kaposi’s sarcoma Phase II (MMPI) Princeton, NJ (212) 546-4000 halofuginone National Cancer Institute AIDS-related Kaposi’s sarcoma Phase II Bethesda, MD N C I T R I A L Collgard Biopharmaceuticals (800) 4-CANCER Atlanta, GA interleukin-12 National Cancer Institute AIDS-related Kaposi’s sarcoma Phase II Bethesda, MD N C I T R I A L (800) 4-CANCER Rituxan™ National Cancer Institute HIV-associated lymphomas Phase II rituximab Bethesda, MD N C I T R I A L IDEC Pharmaceuticals (800) 4-CANCER San Diego, CA A N T I F U N G A L S Product Name Sponsor Indication Development Status 0.5% C31G Biosyn oral infections associated with Phase I/II oral rinse Philadelphia, PA immune suppression (215) 387-5338 DB 289 Immtech International Pneumocystis carinii pneumonia Phase II Vernon Hills, IL (PCP) (847) 573-0033 (see also anti-infectives) micafungin Fujisawa Healthcare invasive fungal infections application submitted (FK463) Deerfield, IL (800) 727-7003 Noxafil Schering-Plough opportunistic fungal infections Phase III posaconazole Kenilworth, NJ (908) 298-40000 A N T I - I N F E C T I V E S Product Name Sponsor Indication Development Status dapsone Jacobus Pharmaceutical Pneumocystis carinii pneumonia Phase III completed Princeton, NJ (PCP) prophylaxis (609) 921-7447 dapsone and Jacobus Pharmaceutical PCP and toxoplasmosis Phase III completed pyrimethamine Princeton, NJ prophylaxis (609) 921-7447 and folinic acid dapsone with Jacobus Pharmaceutical PCP treatment Phase III completed trimethoprim Princeton, NJ (609) 921-7447 2 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 HIV/AIDS 2003 * For more information about a specific medicine in this report, please call the telephone number listed. A N T I - I N F E C T I V E S Product Name Sponsor Indication Development Status DB 289 Immtech International PCP Phase II Vernon Hills, IL (see also antifungals) (847) 573-0033 GEM® 92 Hybridon HIV infection Phase I Cambridge, MA (617) 679-5593 SPD705 Shire Pharmaceutical opportunistic infections Phase I Development (240) 453-6400 Rockville, MD Ushercell Polydex Pharmaceuticals prevention of HIV infection and Phase I/II Toronto, Ontario other sexually transmitted diseases (416) 755-2231 A N T I V I R A L S Product Name Sponsor Indication Development Status 640385 GlaxoSmithKline HIV infection Phase I (VX-385) Philadelphia, PA (888) 825-5249 (aspartyl protease Rsch. Triangle Park, NC inhibitor) Vertex Pharmaceuticals Cambridge, MA 678248 GlaxoSmithKline HIV infection Phase I (NNRTI) Philadelphia, PA (888) 825-5249 Rsch. Triangle Park, NC 695634 GlaxoSmithKline HIV infection Phase I (NNRTI) Philadelphia, PA (888) 825-5249 Rsch. Triangle Park, NC 810781 GlaxoSmithKline HIV infection Phase II (integrase Philadelphia, PA (888) 825-5249 inhibitor) Rsch. Triangle Park, NC (973) 966-6900 873140 GlaxoSmithKline HIV infection Phase I (ONO-4128) Philadelphia, PA (888) 825-5249 (CCR5 antagonist) Rsch. Triangle Park, NC AG-1859 Pfizer HIV positive Phase I New York, NY (860) 732-6058 Alferon N Hemispherx Biopharma 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 AMD070 AnorMed HIV infection treatment Phase I Vancouver, BC (604) 530-1057 amdoxovir Gilead Sciences HIV disease treatment Phase II (DAPD) Foster City, CA (650) 574-3000 (purine nucleoside analog) Anticort™ Samaritan Pharmaceuticals HIV infection Phase II completed procaine HCl Las Vegas, NV (702) 735-7001 3M E D I C I N E S I N D E V E L O P M E N T F O R HIV/AIDS 2003 A N T I V I R A L S Product Name Sponsor Indication Development Status Beta-L-Fd4C Achillion Pharmaceuticals HIV infection Phase II West Haven, CT (203) 624-7000 calanolide A Sarawak MediChem HIV infection Phase II (NNRTI) Pharmaceuticals and (630) 739-6744 Advanced Life Sciences Woodbridge, IL capravirine Pfizer HIV infection/AIDS Phase II (NNRTI) New York, NY (860) 732-6058 CCR5 receptor Schering-Plough HIV infection Phase I antagonist Kenilworth, NJ (908) 298-4000 entecavir Bristol-Myers Squibb HIV & hepatitis B co-infection Phase III (BMS 200475) Princeton, NJ (212) 546-4000 Epivir® GlaxoSmithKline HIV infection Phase III lamivudine Philadelphia, PA (888) 825-5249 Ziagen® Rsch. Triangle Park, NC abacavir (combination tablet) GS 7340 Gilead Sciences HIV infection/AIDS Phase I Foster City, CA (650) 574-3000 IFN-alpha lozenge Amarillo Biosciences treatment of oral warts in Phase III (natural human Amarillo, TX HIV-seropositive patients (806) 376-1741, ext. 22 interferon-alpha) (see also immunomodulators) (Orphan Drug) ME-609 Medivir oral herpes Phase I Huddinge, Sweden 46-8-608-3100 MIV-310 Medivir multi-resistant HIV infection Phase II Huddinge, Sweden 46-8-608-3100 Multikine® CEL-SCI HIV/human papillomavirus Phase I leukocyte Vienna, VA co-infection in women with (703) 506-9460 interleukin cervical dysplasia injection (see also immunomodulators) PCL-016 Novactyl herpes labialis (cold sores), Phase II St. Louis, MO herpes genitalis (genital herpes) (800) 654-2299 Upsher-Smith Laboratories Maple Grove, MN peptide T Avanced Immuni T HIV infection Phase II Stony Brook, NY PRO 542 Progenics Pharmaceuticals HIV infection Phase II Tarrytown, NY (914) 789-2800 R724 Roche HIV infection Phase II (T-1249) Nutley, NJ (973) 235-5000 (fusion inhibitor) Trimeris (919) 419-6050 Durham, NC R944 Roche HIV disease Phase I (PI) Nutley, NJ (973) 235-5000 4 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 HIV/AIDS 2003 A N T I V I R A L S Product Name Sponsor Indication Development Status SPD754 Shire Pharmaceutical HIV infection Phase II Development (240) 453-6400 Rockville, MD SPD756 Shire Pharmaceutical HIV infection Phase I Development (240) 453-6400 Rockville, MD tipranavir Boehringer Ingelheim HIV infection Phase III (PI) Pharmaceuticals (203) 798-9988 Ridgefield, CT TMC114 Tibotec HIV infection Phase I/II (PI) Yardley, PA TMC125 Tibotec HIV infection Phase II (NNRTI) Yardley, PA UK-427,857 Pfizer HIV positive Phase II New York, NY (860) 732-6058 Viread® Gilead Sciences once-daily regimen for the treatment Phase III tenofovir disoproxil Foster City, CA of HIV infection in combination (650) 574-3000 fumarate with Emtriva™ (lemtricabine) and efavirenz versus a regimen with Combivir® (lamivudine/zidovudine) and efavirenz I M M U N O M O D U L A T O R S Product Name Sponsor Indication Development Status Alferon N Hemispherx Biopharma 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 Phase II Philadelphia, PA (salvage therapy) (215) 988-0080 -------------------------------------------------------------------------------------- HIV infection Phase II (strategic treatment intervention) (215) 988-0080 BAY 50-4798 Bayer HIV infection Phase I West Haven, CT (800) 468-0894 IFN-alpha lozenge Amarillo Biosciences treatment of oral warts in Phase III (natural human Amarillo, TX HIV-seropositive patients (806) 376-1741, ext. 22 interferon-alpha) (see also antivirals) (Orphan Drug) IMMUNITIN™ Hollis-Eden HIV infection/AIDS Phase II (HE2000) Pharmaceuticals (858) 587-9333 San Diego, CA MDX-010 Medarex HIV infection Phase I Princeton, NJ (908) 479-2400 5M E D I C I N E S I N D E V E L O P M E N T F O R HIV/AIDS 2003 I M M U N O M O D U L A T O R S Product Name Sponsor Indication Development Status Multikine® CEL-SCI HIV/human papillomavirus Phase I leukocyte Vienna, VA co-infection in women with (703) 506-9460 interleukin cervical dysplasia injection (see also antivirals) SGN 00101 StressGen Biotechnologies genital warts Phase II Victoria, British Columbia (800) 661-4978 WF10 Dimethaid Research late-stage HIV disease Phase III Markham, Ontario (905) 415-1446 V A C C I N E S Product Name Sponsor Indication Development Status AG-702 Antigenics genital herpes Phase I New York, NY (212) 332-4774 AIDS vaccine United Biomedical HIV infection Phase I Hauppauge, NY (631) 273-2828 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 III (vCP1521) Swiftwater, PA immunotherapy (570) 839-4267 AVX101 AlphaVax HIV infection Phase I (HIV vaccine) Rsch. Triangle Park, NC (919) 595-0400 EP HIV-1090 Epimmune HIV-1 therapy Phase I San Diego, CA (858) 860-2515 genital herpes AuRx treatment of genital herpes Phase I/II completed vaccine Glen Burnie, MD (410) 590-7610 HIVA.DNA-MVA International AIDS HIV-1 prophylaxis Phase I/II Vaccine Initiative (212) 847-1111 New York, NY HIV recombinant GlaxoSmithKline HIV prophylaxis Phase I vaccine Philadelphia, PA (888) 825-5249 Rsch. Triangle Park, NC HIV vaccine Emory Vaccine Center HIV infection Phase I Atlanta, GA GeoVax Atlanta, GA NIAID Bethesda, MD HIV vaccine Merck prevention and treatment of HIV Phase I Whitehouse Station, NJ infection/AIDS (800) 672-6372 recombinant Therion Biologics AIDS Phase I vaccine Cambridge, MA (617) 475-7253 Simplirix GlaxoSmithKline genital herpes prophylaxis Phase III recombinant Philadelphia, PA (888) 825-5249 vaccine Rsch. Triangle Park, NC 6 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 HIV/AIDS 2003 V A C C I N E S Product Name Sponsor Indication Development Status tat toxoid Aventis Pasteur HIV infection prophylaxis and Phase I Swiftwater, PA immunotherapy (570) 839-4267 O T H E R S Product Name Sponsor Indication Development Status 1.0% C31G Biosyn prevention of HIV transmission and Phase II/III vaginal gel Philadelphia, PA other sexually transmitted diseases (215) 387-5338 AVR118 Advanced Viral Research HIV infection Phase I/II Yonkers, NY (914) 376-7383 buffer gel ReProtect prevention of sexual transmission Phase II (microbicide) Baltimore, MD of HIV infection (410) 516-7260 HGTV43 Enzo Biochem HIV-1 infection Phase I/II (gene medicine) Farmingdale, NY (631) 755-5500 HIV therapeutic United Biomedical block progression from Phase I Hauppauge, NY HIV infection to AIDS (631) 273-2828 NEUPOGEN® Amgen treatment of neutropenia application submitted filgrastim Thousand Oaks, CA in HIV-infected patients (805) 447-1000 (G-CSF) NGX-4010 NeurogesX painful HIV-associated neuropathy Phase II/III San Carlos, CA (650) 508-2116 PRO 2000 Indevus Pharmaceuticals prevention of HIV infection Phase II/III Lexington, MA transmission (intravaginal gel) (781) 861-8444 prosaptide Savient Pharmaceuticals HIV-associated neuropathic pain Phase II East Brunswick, NJ (800) 284-2480 rhlGF-1/rhlGFBP-3 Insmed AIDS lipodistrophy Phase II Richmond, VA (804) 565-3000 Serostim™ Serono HIV-associated adipose Phase III somatropin (rDNA Rockland, MA redistribution syndrome (800) 283-8088 origin) for injection (Orphan Drug) UC-781 Biosyn prevention of sexually-transmitted Phase I (microbicide) Philadelphia, PA HIV (215) 387-5338 VRX496 VIRxSYS HIV infection Phase I Gaithersburg, MD The content of this survey has been obtained through government and industry sources based on the latest informa- tion. Survey current as of November 7, 2003. The information may not be comprehensive. For more specific information about a particular product, contact the individual company directly. The entire series of “Medicines in Development” is available on PhRMA’s web site. PhRMA Internet address: http://www.phrma.org Provided as a Public Service by PhRMA. Founded in 1958 as the Pharmaceutical Manufacturers Association. Copyright © 2003 by the Pharmaceutical Research and Manufacturers of America. Permission to reprint is awarded if proper credit is given. 7M E D I C I N E S I N D E V E L O P M E N T F O R HIV/AIDS 2003 A P P R O V E D M E D I C I N E S F O R H I V I N F E C T I O N / A I D S Product Name Company Indication Agenerase® GlaxoSmithKline HIV infection/AIDS amprenavir Philadelphia, PA (PI) Rsch. Triangle Park, NC Vertex Pharmaceuticals Cambridge, MA Combivir® GlaxoSmithKline HIV infection lamivudine/ Philadelphia, PA zidovudine tablets Rsch. Triangle Park, NC (NRTI) Crixivan® Merck HIV infection indinavir sulfate Whitehouse Station, NJ (PI) Emtriva™ Gilead Sciences treatment of HIV-1 infection in adults in combination with other emtricitabine Foster City, CA antiretroviral medications (NRTI) Epivir® GlaxoSmithKline HIV infection, HIV infection (once-daily dosing) lamivudine (3TC) Philadelphia, PA (NRTI) Rsch. Triangle Park, NC BioChem Pharma Laval, Quebec Fortovase® Roche treatment of HIV infection in adults in combination with saquinavir Nutley, NJ other antiretroviral agents mesylate (PI) (soft gel formulation) Fuzeon® Roche HIV infection/AIDS enfuvirtide Nutley, NJ Trimeris Durham, NC Gamimune®-N Bayer pediatric HIV infection immune globulin Berkeley, CA intravenous (human) HIVID® Roche in combination with other antiviral agents for treatment of zalcitabine Nutley, NJ HIV infection (NRTI) Invirase® Roche treatment of HIV infection in combination with other saquinavir mesylate Nutley, NJ antiviral agents (PI) Kaletra® Abbott Laboratories treatment of HIV infection in adults and children lopinavir/ritonavir Abbott Park, IL (PI) Lexiva™ GlaxoSmithKline treatment of HIV infection in combination with other fosamprenavir Philadelphia, PA antiretroviral medications calcium Rsch. Triangle Park, NC (PI) Vertex Pharmaceuticals Cambridge, MA Norvir® Abbott Laboratories HIV infection (pediatric and adult) ritonavir Abbott Park, IL (PI) 8 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 HIV/AIDS 2003 A P P R O V E D M E D I C I N E S F O R H I V I N F E C T I O N / A I D S Product Name Company Indication Rescriptor® Agouron Pharmaceuticals, HIV infection/AIDS delvaridine a Pfizer Company (NNRTI) La Jolla, CA Retrovir® GlaxoSmithKline HIV positive (asymptomatic [CD4<500] and symptomatic zidovudine (AZT) Philadelphia, PA [ARC, AIDS]), pediatric and adult, prevention of maternal/fetal (NRTI) Rsch. Triangle Park, NC transmission of HIV infection Reyataz™ Bristol-Myers Squibb treatment of HIV-1 infection in combination with other atazanavir sulfate Princeton, NJ antiretroviral medications (PI) Sustiva® Bristol-Myers Squibb HIV infection efavirenz Princeton, NJ (NNRTI) Sustiva® Bristol-Myers Squibb HIV infection efavirenz Princeton, NJ (once-daily) (NNRTI) Trizivir® GlaxoSmithKline HIV infection treatment abacavir, Philadelphia, PA lamivudine and Rsch. Triangle Park, NC zidovudine combination tablet (NRTI) VIDEX® Bristol-Myers Squibb HIV infection, pediatric HIV infection, once-daily dosing didanosine (ddI) Princeton, NJ (NRTI) VIDEX® EC Bristol-Myers Squibb HIV infection didanosine (ddI) Princeton, NJ (NRTI) Viracept® Agouron Pharmaceuticals, HIV infection/AIDS (pediatric and adult) nelfinavir mesylate