摘要:

Influenza virus infections in high risk individuals, such as infants, the elderly, and patients with cardiopulmonary disorders or immunocompromised states, cause severe manifestations which often result in fatalities. The emergence of a new antigen type of influenza A virus (H5N1) in Hong Kong during 1997 and 1998 threatened a possible pandemic of a new influenza infection.The investigation for anti-influenza chemotherapies has progressed in the last decade whereas clinical trials of new compounds have been limited to amantadine, rimantadine and ribavirin. Fusion inhibitors which directly inhibit conformational change of haemagglutinin (HA), protease inhibitors which inhibit cleavage of HA to HA1 and HA2, RNA transcription inhibitors which inhibit cap formation of mRNA and antisense oligonucleotides targeted at mRNA of PB2 (a part of viral RNA polymerase) have been reported, in their development phases.Recently, 2 neuraminidase (NA) inhibitors, zanamivir and oseltamivir (GS 4104), were used in clinical trials for the treatment of patients with influenza. Both agents showed promising results. A polyoxometalate, PM-523, inhibits fusion between the virus envelope and cell membrane and inhibits the penetration of the virus into cells. This compound has shown potent anti-influenza activity and synergistic inhibitory activity in combination with ribavirin or zanamivirin vitroandin vivo.Resistant strains for zanamivir, oseltamivir or PM-523 have been isolated. The analysis of mutation points of these strains have contributed to the investigation of the antiviral mechanisms of action of these compounds and the mechanism of resistance of the mutants to these compounds.

ISSN:1174-5886    

出版商:ADIS    

年代:1999

数据来源: ADIS

摘要:

All drugs appearing in the Adis Profile Summary table have been selected based on information contained inR&D InsightTM, a proprietary product of Adis International. As the emphasis ofDrugs in R&Dis on the clinical potential of new drugs, selection of agents for full profile is based on the extensiveness of available data. Information on all drugs in clinical development, as identified fromR&D InsightTM, is included in the summary table. Information and/or profiles of agents in preclinical development may be included as appropriate.

ISSN:1174-5886    

出版商:ADIS    

年代:1999

数据来源: ADIS

摘要:

Arbidol is an antiviral and immunostimulatory agent developed in the Russian Research Chemical-Pharmaceutical Institute. It has been launched in the Russian Federation for the prophylaxis and treatment of influenza A and B. The mechanism of action of arbidol has not been completely clarified, but it appears that the compound inhibits influenza virus/cell fusion, as well as inducing interferon and activating macrophage phagocytic function. The antiviral effect may be related to activation of 2,5-oligoadenylate synthetase. Arbidol may also be beneficial for patients with secondary immunodeficiency, in those with recurrent herpes infection and in those with chronic bronchitis.

ISSN:1174-5886    

出版商:ADIS    

年代:1999

数据来源: ADIS

摘要:

&NA;Oseltamivir (EN241104, RO640796, GS 4104, Tamiflu) is the lead compound from a group of carbocyclic compounds developed by Gilead Sciences and the University of California, Berkeley in collaboration with The Australian National University, Canberra. Oseltamivir is the ethyl ester prodrug of GS 4071, a potent and selective inhibitor of the influenza neuraminidase enzyme with low (< 5%) oral bioavailability. Oseltamivir has lipophilic properties and exhibits rapid enzymatic conversion to GS 4071.Roche has submitted an NDA with the FDA in the US, where oseltamivir will be marketed as Tamiflu. The company anticipates the application will receive a 6-month priority review. Regulatory filings have also been submitted in the European Union, Canada, and Switzerland. Oseltamivir is undergoing phase III clinical studies involving a variety of patients, including senior citizens, adults at risk of developing complications from the flu, healthy children as young as 1 year and children with asthma, in Australia, New Zealand, Hong Kong, South Africa and South America. Pivotal studies were initiated in Japan in the first quarter of 1999.Gilead has entered into an agreement with Roche for the development and marketing of influenza therapies. Under this agreement, Roche gained exclusive worldwide rights to Gilead's neuraminidase inhibitors, of which oseltamivir is the lead candidate. Roche is to pay Gilead $US10 million up front and a further $US40 million in milestone payments for worldwide marketing rights. In addition, Roche will fund all research and development costs and pay Gilead royalties on sales of marketed compounds.Oseltamivir has potent, broad spectrum activity against multiple strains of influenza A and B viruses, verified by clinical studies. Oseltamivir has demonstrated effectiveness in both the treatment and prevention of naturally occurring infections and compared with zanamivir, oseltamivir has the advantage of being administered orally. Oseltamivir could also potentially be a useful adjunct to the flu vaccine.

ISSN:1174-5886    

出版商:ADIS    

年代:1999

数据来源: ADIS

摘要:

&NA;Zanamivir (4-guanidino Neu5Ac2en, GG 167, GR 121167, GR 121167X, RelenzaTM) is a neuraminidase inhibitor, developed at Monash University, Australia, for the treatment and prophylaxis of influenza A and B virus infections. Glaxo Wellcome acquired worldwide development and marketing rights from Biota Holdings, the Australian company that funded the original research at Monash.Zanamivir received approval in the European Union (EU) for the treatment of influenza A and B virus infections through the mutual recognition procedure following its first regulatory approval in February 1999 in Sweden. Sweden acted as the Reference Member State for obtaining approval in other countries in the EU. As Swedish authorities would not approve zanamivir for prevention of influenza, Glaxo Wellcome is conducting further clinical evaluations for this indication. An application for the prevention of influenza is expected later in 1999. Zanamivir has been launched in Australia and New Zealand for the treatment of influenza and has been approved in Switzerland for this indication. Applications for approval have been submitted in Canada and Japan, and the drug is in phase III development in South Africa. In the US, zanamivir has been approved for the treatment of influenza after initial reservations about clinical end-points and the efficacy of zanamivir resulting in the drug not being recommended for approval by the US Food and Drug Administration (FDA) Antiviral Drugs Advisory Committee. The committee expressed concern about 2 studies demonstrating significant efficacy conducted outside the US. The FDA extended the regulatory review for zanamivir following discussions with Glaxo Wellcome.A systemically administered IV formulation of zanamivir is being evaluated in phase III trials in the US for use in seriously ill patients who may find inhaled administration difficult or ineffective. Zanamivir is poorly absorbed from the gastrointestinal tract and therefore cannot be administered as an oral preparation.Zanamivir is the first orally inhaled neuraminidase inhibitor that has potent and selective activity against both influenza A and B viruses. Compared with existing therapies, zanamivir is effective for both prophylaxis and treatment of influenza infections, has a reduced risk of adverse events as the drug acts directly on the influenza virus at the site of infection, and less potential for generating drug-resistant strains. For at-risk individuals who would benefit most, such as the elderly, the potential of zanamivir has yet to be demonstrated. IV administration of zanamivir may be useful for patients for whom inhalation is difficult or ineffective.

ISSN:1174-5886    

出版商:ADIS    

年代:1999

数据来源: ADIS

摘要:

All drugs appearing in the Adis Profile Summary table have been selected based on information contained inR&D InsightTM, a proprietary product of Adis International. As the emphasis ofDrugs in R&Dis on the clinical potential of new drugs, selection of agents for full profile is based on the extensiveness of available data. Information on all drugs at preregistration or phase III of clinical development, as identified fromR&D InsightTM, is included in the summary table.

ISSN:1174-5886    

出版商:ADIS    

年代:1999

数据来源: ADIS

摘要:

Development of oral inactivated vaccines againstVibrio choleraeis associated with nonindustrial centres worldwide, including the International Centre for Diarrhoeal Disease Research (Bangladesh), University of Göteborg (Sweden), Mahidol University (Thailand), University of Maryland (USA), National Institutes of Health (USA) and the Walter Reed Army Institute of Research (USA).Researchers at the Mahidol University in Thailand have conducted clinical trials investigating the immunogenicity of their oral inactivated cholera vaccine.Researchers at the National Institute of Hygiene and Epidemiology in Hanoi, in Vietnam and the National Institute of Child Health and Human Development in Bethesda, Maryland, USA, are also conducting phase III clinical trials in Vietnam using a killed whole-cell vaccine, based onV. cholerae01 El Tor biotype. The vaccine is said to be effective and inexpensive but confers protection only against the 01 serogroup of cholera. The researchers were seeking to modify the vaccine further by the addition of killed 0139 cholera strain to the existing formulation. It appears that the government of Vietnam has now modified its whole-cell vaccine by adding a killedV. cholerae0139 strain to the existing vaccine formulation and phase II trials with the bivalent vaccine were to begin in 1997.

ISSN:1174-5886    

出版商:ADIS    

年代:1999

数据来源: ADIS

摘要:

SmithKline Beecham has developed a combination vaccine (InfanrixDTPa®-HepB-IPV) against diphtheria, tetanus, pertussis, hepatitis B and poliovirus. On 19 July 1999, SmithKline Beecham announced that it had submitted a biologics licence application to the US Food and Drug Administration for InfanrixDTPa®-HepB-IPV. If the submission is approved, this vaccine will be the first pentavalent vaccine (targeting 5 diseases) to be licensed in the US, and will reduce from 9 to 3 the number of injections a child should receive in the first year of life to gain protection from diphtheria, tetanus, whooping cough, hepatitis B and polio. More than 20 000 doses of InfanrixDTPa®-HepB-IPV have been administered as a 3-dose series in clinical trials designed to demonstrate that the safety and immunogenicity of the combination vaccine are comparable to those of individual vaccine components given separately.

ISSN:1174-5886    

出版商:ADIS    

年代:1999

数据来源: ADIS

摘要:

Prophylactic vaccines against the arenavirus infection causing haemorrhagic fever are currently undergoing preclinical to phase III development trials.Researchers at the Chinese Academy of Preventive Medicine and the Changchum Institute of Biological Products (China) are pursuing phase I clinical development of a bivalent inactivated golden hamster kidney cell culture vaccine against haemorrhagic fever with renal syndrome. This vaccine is also in phase I trials in Japan and North Korea and in phase III trials in South Korea.A live attenuated virus vaccine against Argentine haemorrhagic fever (Junin strain) appears to be undergoing phase I investigation at the US Army Medical Research Institute of Infectious Diseases (USA) and at the Istituto Nacional de Estudios sobre Virosis Hemorragicas (Argentina).Preclinical studies of Oxford Virology's chimeric vaccine against haemorrhagic fever were being conducted at the University of Ottawa (Canada). However, no recent development has been reported.

ISSN:1174-5886    

出版商:ADIS    

年代:1999

数据来源: ADIS

摘要:

The pre-S1 and -S2 domains are thought to be important factors in the immunogenicity of hepatitis B virus vaccines. A recombinant hepatitis B virus vaccine (Bio-Hep-BTM,Sci-B-Vac®) which expresses all the antigenic epitopes and domains of the hepatitis B virus envelope, including the S1, pre-S1 and pre-S2 antigens, was produced from Chinese hamster ovary cells at the Weizmann Institute in Israel, in association with Yeda. (Yeda is the commercial arm of the Weizmann Institute.) However, all development and marketing rights to the vaccine have been transferred to Bio-Technology General in the US, and Scitech holds a licence for all Pacific Rim countries excluding China and Japan.Bio-Technology General's vaccine is in preregistration in Israel, phase III clinical trials in the US, and is undergoing or has undergone clinical trials in India, Singapore, Thailand and the Commonwealth of Independent States (former USSR). The vaccine is available for licensing in China, Europe, Japan, Mexico, Central and South America, and the US. It appears that Bio-Technology General has also entered into a development and licensing agreement with Swiss Serum and Vaccine Institute in Berne, Switzerland for Western Europe, most of Latin America and various other countries. Bio-Technology General will receive milestone payments from Swiss Serum and Vaccine Institute as well as royalties on sales of the vaccine.The company believes that Bio-Technology General's vaccine is a cost-effective alternative to other hepatitis B vaccines in the market. Bio-Technology General's vaccine elicits a quicker immune response and provides protection with lower doses than existing commercial vaccines.

ISSN:1174-5886    

出版商:ADIS    

年代:1999

数据来源: ADIS