| |
New CCR5 Drug Starts Phase I in Patients
|
| |
| |
Human Genome Sciences issued this press announcement regarding the start of study of their CCR5 entry inhibitor drug.
"HUMAN GENOME SCIENCES RECEIVES FDA CLEARANCE TO INITIATE CLINICAL DEVELOPMENT OF A NEW COMPOUND FOR THE TREATMENT OF HIV/AIDS"
ROCKVILLE, Maryland -- January 10, 2005 -- Human Genome Sciences, Inc. (Nasdaq: HGSI) announced today that it has received clearance from the U.S. Food and Drug Administration (FDA) of its Investigational New Drug (IND) application to begin clinical trials of CCR5 mAb for the treatment of HIV/AIDS. CCR5 mAb (CCR5mAb004) is a fully human monoclonal antibody that specifically recognizes and binds the chemokine receptor CCR5.1-2 The CCR5 receptor is known to be a key facilitator of infection with human immunodeficiency virus (HIV-1), the retrovirus that causes acquired immunodeficiency syndrome (AIDS).3-7
Human Genome Sciences now plans to proceed with a Phase 1 clinical trial to evaluate the safety, tolerability and pharmacology of CCR5 mAb in patients who are infected with HIV-1. The Phase 1 trial will be a randomized, placebo-controlled, dose-escalation, multi-center study. The primary objective of the study will be to evaluate the safety and tolerability of escalating doses of a single intravenous (IV) infusion of CCR5 mAb. The secondary objectives of the Phase 1 study will be to determine the pharmacokinetics of CCR5 mAb, and to assess its effect on plasma HIV-1 viral load and on CD4+ and CD8+ T-cell counts over time.
The CCR5 receptor is a co-receptor on the cell surface that, together with CD4, mediates the binding of HIV-1 and its entry into the cell. Research has shown that the CCR5 receptor is the primary co-receptor for enabling HIV-1 transmission and replication from the early stages of disease through progression to AIDS.3-7 Research also has demonstrated that people who lack a functional CCR5 receptor are resistant to HIV infection or have slower HIV/AIDS disease progression, and that blocking the biological function of CCR5 with antagonists or chemokines can inhibit HIV replication.8-17 Preclinical studies of CCR5 mAb demonstrate that it binds specifically and with high affinity to human CCR5, prevents HIV-1 entry, demonstrates no agonistic activity or effector functions, and has a prolonged serum half-life.1-2
David C. Stump, M.D., Executive Vice President, Drug Development, said, "I am pleased that we are now able to initiate a Phase 1 clinical trial of CCR5 mAb for use in the treatment of patients who are infected with HIV-1. HIV infection is a serious threat to health that continues to grow worldwide. There is a great need for novel therapeutic options, particularly given the continuing emergence of HIV resistance to currently available therapies. We believe that CCR5 mAb has the potential to provide a novel therapeutic option for the treatment of HIV infection and AIDS, which may offer the advantages of a lack of drug interactions and a reduced likelihood of the development of resistance."
Craig A. Rosen, Ph.D., President and Chief Operating Officer, said, "The ability of CCR5-receptor inhibitors to block CCR5's biological function and inhibit HIV replication has been widely reported. Our preclinical studies demonstrate that CCR5 mAb exhibits a number of characteristics that support advancing it to clinical development, including potent inhibition of CCR5-dependent entry of HIV-1 viruses into human cells, and inhibition of cell-cell fusion and viral transmission."
H. Thomas Watkins, Chief Executive Officer, said, "Human Genome Sciences set as a milestone the goal of entering 1-2 new drugs into clinical development in 2004. The FDA's December 2004 authorization of the first clinical study of CCR5 mAb in patients infected with HIV-1 completes our achievement of this important milestone. In August 2004, we began the first clinical study of another new drug, HGS-TR2J, in patients with advanced cancer. It is our hope that patients one day will benefit significantly from both of these novel therapeutic candidates. I am particularly pleased with the productivity of our research scientists.
CCR5 mAb is a fully human monoclonal antibody generated by Human Genome Sciences using the Abgenix XenoMouse® technology. Human Genome Sciences acquired an exclusive worldwide license from Abgenix in 2003 to develop and commercialize a fully human monoclonal antibody to the CCR5 receptor.18 Under the terms of a 1999 agreement, which was amended in 2001, Human Genome Sciences will pay clinical development milestone payments and royalties to Abgenix if a CCR5 mAb is successfully developed and commercialized under the agreement.19 CCR5 mAb will be manufactured in the Human Genome Sciences clinical manufacturing facility in Rockville, MD.
Health professionals or patients interested in inquiring about clinical trials involving Human Genome Sciences products are encouraged to inquire via the Contact Us section of the company's web site, www.hgsi.com/products/request.html, or by calling us at (301) 610-5790, extension 3550. For additional information about Human Genome Sciences, please visit our web site at www.hgsi.com.
Human Genome Sciences is a company with the mission to treat and cure disease by bringing new gene-based protein and antibody drugs to patients.
HGS and Human Genome Sciences are trademarks of Human Genome Sciences, Inc. XenoMouse is a registered trademark of Abgenix, Inc.
This announcement contains forward-looking statements within the meaning of Section 27A of the Securities Act of 1933, as amended, and Section 21E of the Securities Exchange Act of 1934, as amended. The forward-looking statements are based on Human Genome Sciences' current intent, belief and expectations. These statements are not guarantees of future performance and are subject to certain risks and uncertainties that are difficult to predict. Actual results may differ materially from these forward-looking statements because of the Company's unproven business model, its dependence on new technologies, the uncertainty and timing of clinical trials, the Company's ability to develop and commercialize products, its dependence on collaborators for services and revenue, its substantial indebtedness and lease obligations, its changing requirements and costs associated with planned facilities, intense competition, the uncertainty of patent and intellectual property protection, the Company's dependence on key management and key suppliers, the uncertainty of regulation of products, the impact of future alliances or transactions and other risks described in the Company's filings with the Securities and Exchange Commission. Existing and prospective investors are cautioned not to place undue reliance on these forward-looking statements, which speak only as of today's date. Human Genome Sciences undertakes no obligation to update or revise the information contained in this announcement whether as a result of new information, future events or circumstances or otherwise.
CONTACTS:
Jerry Parrott
Vice President, Corporate Communications
301/315-2777
Kate de Santis
Director, Investor Relations
301/251-6003
Footnotes:
1. Roschke V, Moore PA, et al. Characterization of novel human monoclonal antibodies that specifically antagonize CCR5 and block HIV-1 entry. 44th Annual Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC), 2004: Abstract #2871.
2. (HGSI Press Release) Human Genome Sciences Characterizes Panel of Novel Human Monoclonal Antibodies that Specifically Antagonize the CCR5 Receptor and Block HIV-1 Entry. November 2, 2004.
3. Liu R, Paxton WA, Chloe S, et al. Homozygous defect in HIV-1 coreceptor accounts for resistance of some multiply exposed individuals to HIV-1 infection. Cell 1996:367-377.
4. Reynes, J, Portales P, Segondy M, et al. CD4+ T cell surface CCR5 density as a determining factor of virus load in persons infected with human immunodeficiency virus type 1. J Infect Dis 2000; 181:927-932.
5. Rottman J, Ganley K, Williams K, Wu L, Mackay C, Ringler D. Cellular localization of the chemokine receptor CCR5: correlation to cellular targets of HIV-1 infection. Amer J Path 1997; 151(5):1341-1351.
6. Schecter A, Calderon T, Berman A, McManus C, Falon J, Rossikhina M, et al. Human vascular smooth muscle cells possess functional CCR5. J of Biol Chem 2000; 275(8):5466-5471.
7. Wu L, Paxton W, Kassam N, Ruffing N, Rottman J, Sullivan N, et al. CCR5 levels and expression pattern correlate with infectability by macrophage-tropic HIV-1, in vitro. J Exp Med 1997 May 5; 185(9):1681-91.
8. Dragic T, Trlola A, Thompson D, Cormier E, Kajumo F, Maxwell E, et al. A binding pocket for a small molecule inhibitor of HIV-1 entry within the transmembrane helices of CCR5. Proc Natl Acad Sci USA 2000; 97(10):5639-5644.
9. Dybul M, Fauci AS, Bartlett JG, Kaplan JE, Pau AK. Guidelines for using antiretroviral agents among HIV-infected adults and adolescents. The Panel on Clinical Practices for Treatment of HIV. Ann Intern Med 2002; 137:381-433.
10. Lalezari JP, Henry K, O'Hearn M, et al. Enfuvirtide, an HIV-1 fusion inhibitor, for drug resistant HIV infection in North and South America. N Engl J Med 2003; 348:2175-2185.
11. Lin P, Blair W, Want T, Spicer T, Guo Q, Zhou N, et al. A small molecule HIV-1 inhibitor that targets the HIV-1 envelope and inhibits CD4 receptor binding. Proc Natl Acad Sci 2003; 100:11013-11018.
12. Pozniak AL, Fätkenheuer G, Johnson M, et al. Effect of short-term monotherapy with UK-427, 857 on viral load in HIV-infected patients. 43rd Annual Interscience Conference on Antimicrobial Agents and Chemotherapy, 2003. Abstract #H-443.
13. Reynes J, Rouzier R, Kanouni T. SCH C: safety and antiviral effects of a CCR5 receptor antagonist in HIV-1-infected subjects. 9th Conference on Retroviruses and Opportunistic Infections, 2002. Abstract #1.
14. Schurmann D, Rouzier R, Nougarede R, et al. SCH D: Antiretroviral activity of a CCR5 receptor antagonist (abstract). 9th Conference on Retroviruses and Opportunistic Infections, 2002.
15. Starr-Spires LD, Collman RG. HIV-1 entry and entry inhibitors as therapeutic agents. Clin Lab Med 2002; 22:681-701.
16. Strizki J, Xu S, Wagner N, Liu J, Hou Y, Endres M, et al. SCH-C (SCH351125), an orally bioavailable, small molecule antagonist of the chemokine receptor CCR5 is a potent inhibitor of HIV-1 infection in vitro and in vivo. Proc Natl Acad Sci USA 2001; 98(22):12718-23.
17. Trkola A, Kuhmann S, Strizki J, Maxwell E, Ketas T, Morgan T, et al. HIV-1 escape from a small molecule, CCR5-specific inhibitor does not involve CXCR4 use. Proc Natl Acad Sci USA 2002; 99(1):395-400.
18. (HGSI Press Release) Human Genome Sciences Acquires License from Abgenix for Human Monoclonal Antibody to Key HIV/AIDS Receptor. May 12, 2003.
(HGSI Press Release) Human Genome Sciences and Abgenix Enter a Broad Collaboration to Create Fully Human
|
|
| |
| |
|
|
|
