摘要:

Acetylcysteine has been shown to enhance the response to interferon-&agr;(IFN&agr;) in patients with hepatitis C and phase II trials are being conducted in Spain and Italy for this indication.Preclinical investigation of acetylcysteine for hepatitis B has been conducted at the Max-Planck-Institut für Biochemie in Germany; however, no further development for this indication has been reported. Acetylcysteine is marketed as Fluimucil® by Zambon and as Mucomyst® by AstraZeneca (formed by the merger of Astra and Zeneca in April 1999) for the treatment of chronic bronchitis. The drug was in phase I/II trials in the US and Spain for the treatment of HIV infection; however, no recent development has been reported.Acetylcysteine is also being investigated in a large clinical study in Italy as a treatment for systemic scleroderma; its antioxidant properties may prevent the effects of oxidative stress in these patients. In addition, preclinical investigation at the University of Occupational and Environmental Health in Japan indicates that acetylcysteine may have potential for the treatment of cadmium cytotoxicity.

ISSN:1174-5886    

出版商:ADIS    

年代:1999

数据来源: ADIS

摘要:

Aldesleukin {Interleukin-2 (IL-2) [Chiron], recombinant IL-2, T cell growth factor, Proleukin®, MacrolinTM} is a recombinant human IL-2 molecule with essentially similar pharmacodynamic properties to endogenous IL-2.Aldesleukin has been developed by Chiron in the US, and has been investigated in phase I/II clinical studies in Spain as a treatment for chronic hepatitis C virus infection.An IV formulation is launched in Europe, the US and South Korea and registered in Canada for the treatment of metastatic renal cell carcinoma, and is registered in Canada and the US for the treatment of metastatic melanoma. A SC formulation of aldesleukin is registered in Israel for the treatment of metastatic renal cell carcinoma, and is preregistered in Europe for the same indication. In the US, aldesleukin is undergoing phase I/II clinical trials for the treatment of ovarian cancer, and phase III trials for HIV-associated non-Hodgkin's lymphoma.Aldesleukin has received orphan drug status for the treatment of primary immunodeficiency disease associated with T cell defects, metastatic renal cell carcinoma and melanoma, acute myelogenous leukaemia (AML) and non-Hodgkin's lymphoma.A pivotal phase III clinical trial of aldesleukin for the treatment of HIV-1 infections has commenced. Chiron has been granted temporary use in France of MacrolinTMfor the treatment of people with advanced HIV infection, who lack adequate immune reconstitution despite effective antiretroviral treatment.Aldesleukin is being investigated in combination with Maxamine® as a treatment of patients with AML in phase III trials in the US, Europe and Australia.In 1994, Ligand entered into an agreement with Chiron under which Ligand acquired the exclusive right to market and sell Proleukin® for metastatic renal cell carcinoma throughout Canada. Hyup Jin Corporation has marketing rights in South Korea. Ajinomoto, DepoTech (SkyePharma) and Roche also appear to have licenses for aldesleukin.

ISSN:1174-5886    

出版商:ADIS    

年代:1999

数据来源: ADIS

摘要:

Interferon-&agr;-n3 (IFN-&agr;-n3) [&agr;-n3-IF, Alferon LDO®, Alferon N®, Alferon N Gel®] is a natural interferon (IFN) produced by Interferon Sciences from pooled units of human leukocytes which have been induced by incomplete infection with the avian Sendai virus. A US patent has been issued to Interferon Sciences covering the drug and its method of production. Interferon Science has entered into an agreement for the American Red Cross to supply leukocytes for the production of Alferon N® Injection.Phase III trials of IFN-&agr;-n3 (Alferon N® Injection) in the US and Mexico for the treatment of previously untreated patients with chronic active hepatitis C have been completed. Fujimoto is currently conducting phase II clinical studies in Japan for hepatitis C. In addition, a phase II trial in the US is evaluating the tolerability and efficacy of the injectable form of IFN-&agr;-n3 in patients co-infected with HIV and hepatitis C virus in order to treat both conditions simultaneously.Interferon Sciences has completed a phase III study of IFN-&agr;-n3 in HIV-infected patients. As the study's primary efficacy variable, reduction in viral load, was not achieved at the end of treatment, the US Food and Drug Administration (FDA) have indicated that another trial is necessary to further evaluate the efficacy of IFN-&agr;-n3 injection for this indication.An injectable form of IFN-&agr;-n3 (Alferon N® Injection, Altemol®) has been launched in the US, Spain and Mexico for the treatment of genital warts. The product is registered in Austria, Canada, Israel, UK, Germany, Singapore, Hong Kong, China and Malaysia. Interferon Sciences is conducting phase II clinical trials in the USA with the gel formulation of IFN-&agr;-n3 (Alferon N Gel®) in women with intravaginal warts caused by papilloma virus who have recurrent, persistent low or high grade cervical dysplasia.Phase II clinical trials using IFN-&agr;-n3 injection are in progress for the treatment of small cell lung cancer in the US.Interferon Sciences is also planning clinical trials with Alferon N® for treatment of multiple sclerosis and hepatitis B.Phase II trials are underway in Mexico in patients with AIDS-related Kaposi's sarcoma. In the US a liquid low dose oral preparation of IFN-&agr;-n3 (Alferon LDO®) supplied by Interferon Sciences was being tested with 2 other brands and compared to placebo by the National Institutes of Allergy and Infectious Diseases in a phase III trial in AIDS patients.

ISSN:1174-5886    

出版商:ADIS    

年代:1999

数据来源: ADIS

摘要:

MaxamineTMis a dihydrochloride salt form of histamine which specifically blocks the phagocyte signal that leads to apoptosis of natural killer (NK) cells. MaxamineTMwas designed by Maxim Pharmaceuticals to enhance the activity of T cell-stimulating and NK cell-stimulating cytokines by inhibiting the production and release of free oxygen radicals. The presence of free oxygen radicalsmay prevent NK cells and T cells from performing their antiviral and antitumour functions.Maxim has commenced a European based phase II trial of MaxamineTMenroling 125 patients with chronic hepatitis C who have not previously received treatment with interferon-&agr;. Four administration regimens will be evaluated in this trial for which patient enrolment was completed in less than 3 months.Combinations of MaxamineTMwith interferons and interleukins, called Maxamine TherapyTM, improve the immune system's ability to identify, disable and destroy malignant or infected cells. Maxim Pharmaceuticals has initiated a phase III clinical trial of Maxamine TherapyTMfor the treatment of acute myeloid leukaemia (AML). Trials will take place in Australia, Canada, Europe and the US and are designed to test Maxamine TherapyTMas AML remission therapy, for which there is currently no standard treatment. Maxamine TherapyTMis also undergoing phase III trials in Australia, Germany, Sweden, the UK and the US for the treatment of malignant melanoma. MaxamineTMis in phase III trials for the treatment of multiple myeloma and renal cell carcinoma in Sweden. Preclinical trials of MaxamineTMin the treatment of prostate cancer are also being conducted in Sweden.The company has entered into an agreement with Amgen to test MaxamineTMin combination with Amgen's Infergen® (interferon consensus) and also Chiron's recombinant interleukin-2 (aldesleukin, Proleukin®). Maxim Pharmaceuticals also has an agreement with BioNative AB and Umea University, Sweden, to test MaxamineTMin a European phase II trial in patients with renal cell carcinoma in combination with BioNative's natural cytokine, Interferon Alfanative®. The trial is based in Sweden, Denmark and the UK and will enrol approximately 40 patients.Maxim Pharmaceuticals has received patents in the US (2 patents), Europe, Australia and Japan for Maxamine® technology. Five additional US patent applications are currently pending.Marketing agreements for MaxamineTMhave been made between Maxim and FH Faulding in Australia and New Zealand, and MegaPharm in Israel.Preliminary results in patients with acute myelogenous leukaemia and chronic hepatitis C have shown MaxamineTMtherapy to be a promising treatment option when compared with inadequate currently available therapies for these patient groups. MaxamineTMcan be self-administered on an outpatient basis, which provides significant advantages.

ISSN:1174-5886    

出版商:ADIS    

年代:1999

数据来源: ADIS

摘要:

It has been reported that the outcome of viral diseases in humans can be influenced by concurrent infection with other viruses. Scientists at the National Institute of Oncology in Budapest, Hungary, have reported the successful use of a therapy for hepatitis B and C, based on the use of a nonpathogenic, genetically engineered Newcastle Disease virus (MTH-68/B).Newcastle Disease virus is a large RNA avian paramyxovirus which causes avian pneumoencephalitis (Newcastle disease). The virus can be transmitted to humans through contact with infected birds but it is considered minimally pathogenic in humans.The MTH-68/B strain shortened the duration of the first icteric phase in patients with acute hepatitis B and C virus. Phase II trials with MTH-68/B have been carried out at Budapest's Szent Laszlo Hospital. Larger scale clinical trials are to be conducted in the future. In addition to these clinical studies, case reports of 3 patients with chronic B and C viral hepatitis who had received MTH-68/B as a therapy indicated that 2 patients were essentially cured within a few months whereas the third moribund patient exhibited significantly improved clinical symptoms. A full 6-month course of treatment with MTH-68/B has been estimated to cost $US400 to 800.The mechanism by which MTH-68 exerts its therapeutic action is not well understood but it appears to involve selective killing of infected cells, either by direct lysis or by stimulation of cytokine release. Although the researchers involved refer to MTH-68 as being a vaccine, the antibodies induced against the virus are not involved in its therapeutic action and may actually inhibit the efficacy of treatment.

ISSN:1174-5886    

出版商:ADIS    

年代:1999

数据来源: ADIS

摘要:

PEG interferon-&agr;-2a (RO 253036, PegasysTM, PEG IFN-&agr;-2a) is a polyethylene glycol (PEG)-modified recombinant human interferon (IFN) developed by Roche using a pegylation process developed by Shearwater Polymers. The process involves attaching one or more hair-like strands of an inert, synthetic polymer to anothermolecule. The PEG attachment encircles the protein and disguises it from the human metabolic system. PEG IFN-&agr;-2a has been designed to avoid some of the problems associated with the short t½ of traditional IFN-&agr;. A short t½ may give the hepatitis C virus the opportunity to recover, replicate and generate resistant forms during the trough periods.Shearwater Polymers has a license agreement with Roche for the PEGylation of IFN-&agr;-2a. This agreement provides Shearwater with up-front payments, rights to manufacture the PEG reagent and a share of downstream revenues.PEG IFN-&agr;-2a is in a phase II trial in noncirrhotic patients, a pivotal phase II study in cirrhotic patients, a phase III study comparing IFN-&agr;-2a to standard dose IFN-&agr; and a phase III study comparing IFN-&agr;-2a to an induction regimen of standard IFN-&agr;. Clinical trials of PEG IFN-&agr;-2a in combination with ribavirin are also in progress. Preliminary results from clinical trials indicate PEG IFN-&agr; may be associated with less toxicity and similar efficacy to IFN-&agr; and ribavirin combination therapy (RebetronTM). It is also being investigated preclinically as an anticancer agent in Switzerland.Weston-Medical, a UK-based drug delivery development company have developed a needle-free injector technology for subcutaneous delivery, Intraject®, which is to be used for the delivery of PEG IFN-&agr;-2a.Enzon filed a patent infringement suit against Shearwater concerning the pegylation technology in December 1998 and litigation is ongoing. Roche have filed for a patent for PEG IFN-&agr;-2a.

ISSN:1174-5886    

出版商:ADIS    

年代:1999

数据来源: ADIS

摘要:

Ursodeoxycholic acid (ursodiol, ursodesoxycholic acid, Urso®, Ursolvan®) is a naturally occurring hydrophilic bile acid that is present in small amounts in human bile. It was first synthesised in Japan in the 1950s for its cholesterol antagonising properties, and has since been used in the treatment of cholesterol gallstone disease. It is marketed in Japan as Urso® by Tokyo Tanabe, a major supplier of ursodeoxycholic acid to Axcan. Ursodeoxycholic acid (Urso®) has had an orphan drug status in the US, where Axcan Pharma has launched it for the treatment of primary biliary cirrhosis. Axcan Schwarz has exclusive marketing rights for Urso® for the treatment of primary biliary cirrhosis for 7 years from the end of 1997. A phase II trial is underway in North America for the treatment of hypercholesterolaemia.Ursodeoxycholic acid is already launched in Canada for primary biliary cirrhosis, and is also launched in Canada and the US (as Actigall®; Novartis) for the dissolution of gallstones. It was marketed as Ursofalk® in Canada by Jouveinal, but this licensing agreement has been terminated since Jouveinal was acquired by Parke-Davis, and the drug is now marketed by Axcan Pharma as Urso®. Ursodeoxycholic acid is also launched in Spain as Ursochol® (Zambon), Ursobilane® (Estedi) and Ursolite® (Vita) for the dissolution of gallstones.Ursodeoxycholic acid is also undergoing phase II clinical trials at the Mayo Clinic, US for the prevention of colorectal cancer and the treatment of hepatitis C. The phase II trial for hepatitis C evaluated Urso® in combination with interferon-&agr;. Ursodeoxycholic acid is in a multicentre phase II trial for non-alcoholic steatohepatitis, and for primary sclerosing cholangitis.Ursodeoxycholic acid has demonstrated immunomodulatory properties, and the ability of Sanofi-Synthélabo's Ursolvan® to prevent acute liver transplant rejection has been tested in clinical trials in France.Axcan has renewed two agreements with Sanofi-Synthélabo for use, manufacture and sale of Urso® because of the expiration in the year 2000 of a previous 10-year agreement. The new licence for the US is valid until the expiration of the patents, in 2008, whereas for Canada, Axcan has acquired all rights on the patent pertaining to primary biliary cirrhosis.Alfa Farmaceutici is developing soluble formulations of ursodeoxycholic acid for the treatment of hepatic diseases and gallstones. The formulations allow targeted delivery of the drug into the first portion of the GI tract where absorption is optimal. Alfa's product is undergoing preclinical development in Italy.

ISSN:1174-5886    

出版商:ADIS    

年代:1999

数据来源: ADIS