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&DInsightTM, 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:

&NA;AMD 3100 (JM 3100, SDZ SID 791) is a bicyclam derivative with potent and selective activity against HIV-1 and HIV-2in vitroand low cytotoxicity. The compound appears to act as a blocker of the CXCR4 chemokine receptor, a crucial co-factor for HIV to infect T lymphocytes. In addition, AMD 3100 appears to inhibit specific events involved in retroviral uncoating and assembly. For these reasons, AMD 3100 is considered the prototype of a new class of antiretroviral agents.AMD 3100 was synthesised by Johnson Matthey (now Anor MED) in collaboration with the Rega Institute of Leuven, Belgium, and was under preclinical investigation with Novartis as SDZ SID 791 for the treatment of HIV infection. However, Novartis returned the rights to the compound and Anor MED has commenced a phase II study at 3 centres in the US including the Johns Hopkins University School of Medicine. This trial is expected to enrol 20 to 30 patients with HIV infection.To date, AMD 3100 has been administered by injection in clinical studies; however, Anor MED has an active development programme for the synthesis of orally active formulations of AMD 3100 and is also developing a subcutaneous form of the drug.

ISSN:1174-5886    

出版商:ADIS    

年代:1999

数据来源: ADIS

摘要:

Dextrin-2-sulfate (D2S, Viraldon®) is a synthetic derivative of dextrin with potent activity against HIV-1. Developed by ML Laboratories, dextrin-2-sulfate is administered via the IP route and is therefore reserved for late stage therapy of HIV-infected patients who have not responded to, or cannot tolerate, other treatments. Aphase III study (TITAN) in the UK is being carried out in which participants are required to be on stable antiretroviral therapy for 3 months before entering the trial and agree to keep up stable treatment for a further 6 months. Centres in South Africa were approached to participate in the study after an initial shortage of eligible patients in the UK, related to the introduction of protease inhibitor tablet treatments. MLLaboratories believed this situation would decline because of a lack of continued efficacy of protease inhibitor treatments combined with unacceptable adverse effects. However, this has not occurred as quickly as the company had expected.ML Laboratories has licensed North American rights to dextrin sulfate to General Medical Industries (GMI) of Virginia, USA. GMI will fund an 80-patient study (ATLAS) in the US as well as other trials necessary for regulatory approval in that country.Dextrin-2-sulfate is available on a compassionate use basis, which will provide additional data for a product licence application scheduled for the last quarter of 2000.An intravaginal gel formulation of dextrin-2-sulfate, Emmelle®, is being developed for the prevention of HIV transmission between heterosexuals. The UK Medical Research Council has adopted Emmelle® as a lead product for this indication. Two phase I evaluations in female volunteers have been completed and recruitment is underway in the UK for a phase II trial in which 200 healthy sexually active female volunteers will be randomised to receive Emmelle® or placebo over 28 days. It is hoped that 50male sexual partnerswill also be recruited to investigate the effect of the product onmen. Further clinical studies are planned in Europe and Africa.Dextrin-2-sulfate exhibited the most favourable combination of high anti-HIV-1 activity and low anticoagulant activity compared with other structural analogues of sulfated polysaccharides. Clinically, however, the need for IP administration limits its usefulness to late-stage HIV-infected patients who have not responded to, or cannot tolerate, other treatments. Once clinical data are available for the intravaginal gel formulation the potential of this product can be more fully evaluated.

ISSN:1174-5886    

出版商:ADIS    

年代:1999

数据来源: ADIS

摘要:

&NA;FP 21399 is an anti-HIV agent member of the naphthalenesulfonic acid family that blocks viral entry to the cell membrane by interacting with the V3 loop of the viral envelope. FP 21399 may cause less toxicity than reverse transcriptase inhibitors as it does not enter the host cells.This agent is an analogue of a compound originally developed by Fuji Photo Film for photographic use. FP 21399 is being developed by Lexigen Pharmaceuticals (Merck KGaA), formerly Fuji Immuno Pharmaceuticals, the US subsidiary of Fuji Photo Film. A phase I clinical study in 30 patients is being conducted at the Beth Israel Hospital, Boston, USA.FP 21399 appears to be a potent anti-HIV agent, targeting an innovative step of the viral life cycle. In addition, its low toxicity and the unique characteristic to concentrate in lymph nodes make it an attractive candidate for clinical trials.

ISSN:1174-5886    

出版商:ADIS    

年代:1999

数据来源: ADIS

摘要:

ISIS 5320 (NSC 665353) is a phosphorothioate oligonucleotide with 4 consecutive guanosines (TTGGGGTT) that form a tetramer stabilised by G quartets. The compound is negatively charged and binds specifically to HIV glycoprotein 120 (gp120) at the V3 loop, preventing cell-to-cell and virus-to-cell infection. After positive results from preclinical studies, Isis Pharmaceuticals has completed phase I clinical trials with ISIS 5320 in the US studying the safety, tolerability and pharmacokinetics of the compound in patients with HIV-1 infection.Under an agreement with AstraZeneca (formed by the merger of Astra and Zeneca in April 1999), supplies of ISIS 5320 for preclinical and initial clinical trials are manufactured by AstraZeneca's Cambridge Research Biochemicals unit. Through a collaborative relationship, the National Cancer Institute in the US was involved in several preclinical studies of ISIS 5302 and provided financial support for the synthesis of sufficient quantities of the compound for toxicology studies and the phase I trial.Once clinical data are available, the potential of ISIS 5320 can be more fully evaluated.

ISSN:1174-5886    

出版商:ADIS    

年代:1999

数据来源: ADIS

摘要:

Pentafuside (T-20, DP 178) is a 36-amino-acid synthetic peptide discovered through a collaboration with Duke University, North Carolina and Trimeris in the US. The amino acid sequence of pentafuside is derived from a domain of the HIV-1 glycoprotein 41 (gp41) fusion protein. The compound is thought to act by preventing HIV from binding to CD4 lymphocytes, thereby blocking infection. Pentafuside, with its patent antiviral activity in preclinical studies and selective inhibition of virus-mediated cell-cell fusion, has received fast-track designation from the FDA.Trimeris has completed phase I/II clinical trials in the US with pentafuside for the treatment of HIV-infected patients.A28-day dose-ranging monotherapy phase II trial (TRI-003) involving 78 patients has been conducted in collaboration with MiniMed comparing the effectiveness of continuous infusion with intermittent injection. Patients from this trial are continuing to receive pentafuside in a long term, open-label rollover protocol. Trimeris has signed a letter of intent with DuPont Merck to conduct an advanced HIV patient trial using efavirenz, DuPont Merck's once-daily, nonnucleoside reverse transcriptase inhibitor, in combination with pentafuside. The trial will enrol up to 48 patients at 3 sites in the US. Patient selection in a phase II trial (T20-206) assessing the antiviral activity and long term tolerability of pentafuside when used in combination with other anti-HIV drugs has commenced. Patients will be evaluated over 1 year using 3 different doses of pentafuside in combination with amprenavir, ritonavir and abacavir as well as efavirenz. This study is expected to enrol up to 68 patients at 12 sites. Pivotal phase III trials are scheduled to begin in 2000 and will evaluate pentafuside in patients who have received extensive antiretroviral therapy as well as those with less treatment experience.In July 1999, Trimeris signed an agreement with Roche for further development of pentafuside and T 1249. Roche and Trimeris will share equally development expenses and profits for these fusion inhibitors in the US and Canada. Elsewhere, Roche will fund all development costs and pay Trimeris a royalty.Given the short half-life of pentafuside, it is believed that the delivery of pentafuside via continuous subcutaneous infusion through MiniMed pumps may provide therapeutic benefits and be a more cost-effective method of administration.Further clinical trials are required to fully assess the safety profile of this agent and to determine if its inconvenient route of administration may be justified by advantages in clinical activity.

ISSN:1174-5886    

出版商:ADIS    

年代:1999

数据来源: ADIS

摘要:

PRO 542 (CD4 IgG2) is a novel tetrameric fusion protein incorporating the HIV-binding region of the human CD4 surface receptor into a human antibody molecule. PRO 542 neutralises HIV by binding to the glycoprotein 120 (gp120) on the viral envelope and preventing the virus from attaching to host cells.PRO 542 is undergoing phase I/II clinical development with Progenics Pharmaceuticals in the US as a post-exposure prophylaxis for exposed health workers and infants born to HIV-positive mothers. The development of PRO 542 is also focusing on treatment during the early or asymptomatic phase of HIV infection. A multi-dose phase I/II paediatric trial of PRO 542 is being sponsored by the AIDS Clinical Trials Group of the National Institute of Allergy and Infectious Diseases.Progenics has entered an agreement with Genzyme Transgenics Corporation for the production of PRO 542 in the milk of transgenic goats, a source claimed to be cost effective and able to provide the product in a timely manner.Progenics has been granted funds for $US2.7 million from the National Institutes of Health to be spent on development of PRO 542 and PRO 367.PRO 542 is a recombinant fusion protein under development both to treat HIV infection and to prevent infection following exposure to the virus. In preclinical studies, the protein potently neutralised a wide range of HIV strains. Initial clinical data indicate the protein has favourable pharmacokinetic parameters, although it needs to be administered intravenously. Once additional clinical data are available, the potential of PRO 542 can be more fully evaluated.

ISSN:1174-5886    

出版商:ADIS    

年代:1999

数据来源: ADIS

摘要:

SPC 3 is a synthetic 8-chain peptide, containing 8 repeats of the consensus region of the V3 loop of HIV-1 glycoprotein 120. It was developed by the Centre Nationale de Reserche Scientifique in Marseilles, France, and has been licensed to Columbia Labs in the US.SPC 3 acts by blocking cell-virus fusion and by blocking the invasion of macrophages. The drug can be used alone or in combination with reverse transcriptase inhibitors to prevent progression to full blown AIDS. Because of the relative specificity of the compound, adverse effects associated with reverse transcriptase and protease inhibitors may be avoided. A phase I/II clinical study is underway at the Roger Williams Medical Center, Rhode Island, USA.

ISSN:1174-5886    

出版商:ADIS    

年代:1999

数据来源: ADIS