摘要:

ObjectiveTo investigate the important factors that determine the bioavailability and the antiviral activity of the diaryltriazine (DATA) and diarylpyrimidine (DAPY) non-nucleoside reverse transcriptase inhibitors (NNRTIs) of HIV-1 in animal species and humans using cell-based assays, physicochemical and computed parameters.MethodsThis naturalistic study included 15 parameters ranging from molecular mechanics calculations to phase I clinical trials. The calculated parameters were solvent-accessible surface area (SASA), polar surface area and Gibbs free energy of solvation. Physicochemical parameters comprised lipophilicity (octanol/water partition coefficient [cLogP]), ionisation constant (pKa), solubility and aggregate radius. Cell-based assays included human colonic adenocarcinoma cell (Caco-2) permeability (transepithelial transport), drug metabolism and antiviral activity (negative logarithm of the molar effective concentration inhibiting viral replication by 50% [pEC50]). Exposure was tested in rats, dogs and human volunteers.ResultsOf the 15 parameters, eight correlated consistently among one another. Exposure (area under the plasma concentration-time curve [AUC]) in humans correlated positively with that in rats (r = 1.00), with transepithelial transport (r = 0.83), lipophilicity (r = 0.60), ionisability (r = 0.89), hydrodynamic radius of aggregates (r = 0.66) and with antiviral activity (r = 0.61). Exposure in humans was also seen to correlate negatively with SASA (r = −0.89). No consistent correlation was found between exposure in dogs and the eight parameters. Of the 14 DATA/DAPY molecules, 11 form aggregates with radii between 34 and 100nm.ConclusionsWe observed correlations between exposure in humans with exposure in rats, transepithelial transport (Caco-2 cells), ionisability, lipophilicity, aggregate radius and SASA in the class of DATA/DAPY NNRTI compounds. The lipophilic DATA/DAPY compounds form aggregates. It can be assumed that absorption in the intestinal tract and endocytosis in infected cells of these lipophilic compounds are governed by the common phenomenon of aggregate formation. As the lymphatic system offers a pathway for intestinal uptake of aggregates, this may offer a therapeutic advantage in the treatment of HIV-1 infection. Although it was not the objective of the study, we found that the rat was a betterin vivomodel than the dog for the prediction of systemic exposure in this particular set of compounds.

ISSN:1174-5886    

出版商:ADIS    

年代:2004

数据来源: ADIS

摘要:

ObjectiveTo study the human risk and benefit of oral pyridoxine (vitamin B6) treatment during pregnancy.Design and settingThe analysis of cases with 25 congenital abnormality (CA) groups and their all-matched controls without CAs in the population-based dataset of the large Hungarian Case-Control Surveillance of Congenital Abnormalities, 1980–1996.Study participants22 843 cases of pregnant women who had newborns or fetuses with CAs and 38 151 pregnant women who had newborn infants without any CAs (control group).Main outcome measuresPrevalence of pyridoxine use in early pregnancy among mothers of cases with different CAs and control mothers with infants without any CA.Results2013 (8.8%) case mothers and 4086 (10.7%) control mothers were treated with pyridoxine (adjusted prevalence odds ratio [POR] 0.8; 95% confidence interval [CI] 0.7, 0.9). The analysis of cases with different defects and their all-matched controls did not indicate any obvious teratogenic potential of pyridoxine use during the second and third months of gestation, i.e. in the critical period for the development of most major CAs. However, some protective effect was found for cardiovascular malformations (adjusted POR 0.8; 95% CI 0.7, 0.9).ConclusionTreatment with pyridoxine during pregnancy does not indicate a teratogenic risk to the fetus, but may provide some protective effect for cardiovascular malformations.

ISSN:1174-5886    

出版商:ADIS    

年代:2004

数据来源: ADIS

摘要:

ObjectiveInterferon (IFN) α-2b is a protein with antiviral, antiproliferative and immunoregulatory properties that is approved for several clinical indications. A new liquid, albumin-free, IFNα-2b formulation has recently been developed. This study aimed to evaluate the equivalence of the pharmacokinetic, pharmacodynamic and safety properties of the new formulation with a reference one in healthy male volunteers.MethodsA randomised, crossover, double-blind study with a 3-week washout period was performed in which Heberon Alfa R®(formulation A) and Viraferon®(formulation B) were compared. A single 20 × 106IU IFNα-2b dose was administered subcutaneously to 14 apparently healthy male subjects. Serum IFN level was measured over 48 hours by enzyme immunoassay (EIA) and by antiviral activity titration. Clinical and laboratory variables were determined, as were pharmacodynamic and safety criteria.ResultsGroups were homogeneous with regard to all demographic and baseline variables. Pharmacokinetic comparison by EIA did not show differences between the formulations: area under the curve (AUC) 2572 versus 2561 ng · h/L, maximum plasma concentration (Cmax) 318 versus 354 ng/L, time to Cmax(tmax) 8.2 versus 8.5h, elimination half-life (t1/2) 5.87 versus 6.08h, terminal elimination rate (λ) 0.122 versus 0.118h-1, and mean residence time (MRT) 10.9 versus 12.0h for formulations A and B, respectively. The differences never reached 20%, which is the clinically significant threshold. The 90% confidence interval of the ratio between them was in all cases within the 0.8, 1.25 range. The two formulations were clinically equivalent with regard to serum IFN antiviral activity titration (0.8, 1.25 criterion) regarding their pharmacokinetic parameters. There were no significant differences with respect to the pharmacodynamic variables: serum β2-microglobulin and temperature increase. Heart rate and blood pressure changes did not differ either. Both products provoked similar haematological count decreases and had similar safety profiles. The most frequent adverse reactions were fever, tachycardia, headache and arthralgias.ConclusionThe overall analysis strongly suggests the bioequivalence of these two products.

ISSN:1174-5886    

出版商:ADIS    

年代:2004

数据来源: ADIS

摘要:

BackgroundDrugs inhibiting cholesterol biosynthesis may affect bone metabolism through inhibition of the mevalonate pathway resulting in the inhibition of protein prenylation required for osteoclast activity. D-003 is a mixture of high molecular weight aliphatic primary acids purified from sugar-cane (Saccharum officinarum) wax, with cholesterol-lowering effects demonstrated in experimental and clinical studies. D-003 inhibits cholesterol biosynthesis through indirect regulation of HMG-CoA reductase activity. A previous study demonstrated that D-003 prevented bone loss and bone resorption on ovariectomy-induced osteoporosis in rats. Corticosteroid-induced osteoporosis is the result of changes affecting calcium homeostasis, but the hallmark of corticosteroid-induced bone loss is the direct effects on bone cells, such as inhibition of osteoblastogenesis, promotion of apoptosis of osteoblasts and osteocytes, and decrease in bone formation.ObjectiveTo determine whether D-003 could prevent the bone loss induced with prednisolone in Sprague-Dawley rats.MethodsRats were randomly distributed in five groups (ten rats per group): a sham-operated control and four groups orally treated with prednisolone 6 mg/kg for 80 days; a positive control orally treated with vehicle; and three groups orally treated with D-003 at 5, 25 and 200 mg/kg, respectively. Rats were killed, bones removed and histological variables of bone resorption and formation studied for histomorphometry.ResultsCompared with the sham group, prednisolone significantly (p < 0.01) reduced trabecular bone volume (TBV), while D-003 significantly (p < 0.001) and dose-dependently prevented the prednisolone-induced reduction of TBV. Treatment with prednisolone lowered (p < 0.001) trabecular thickness (TbTh) and number (TbN), while increasing (p < 0.001) the gap between trabeculae. D-003 (5, 25 and 200 mg/kg/day) significantly (p < 0.001) and dose-dependently prevented the reduction of TbTh and TbN and the increase of trabecular gap induced with prednisolone. Treatment with prednisolone increased both the surface and number of osteoclasts compared with sham (p < 0.001). D-003 (5–200 mg/day), however, prevented this effect (p < 0.001 for all comparisons). D-003 also prevented (p < 0.001) the reduction of osteoblast surface (ObS/BS) induced by prednisolone. Osteonecrotic areas were observed in all positive controls, but in none of the sham animals. Positive controls showed hypertrophy of bone marrow adipocytes and lipid-laden pluripotential stromal cells in bones. A significant and dose-dependent reduction of the frequency of animals showing prednisolone-induced osteo-necrosis was observed across the doses of D-003 (5, 25 and 200 mg/kg) investigated here.ConclusionsD-003 (5, 25 and 200 mg/kg) prevented trabecular bone loss and femoral neck osteonecrosis induced with prednisolone in Sprague Dawley rats, also increasing osteoblast surface and reducing bone resorption parameters. These results suggest that D-003 could be useful for managing corticosteroid-induced osteoporosis.

ISSN:1174-5886    

出版商:ADIS    

年代:2004

数据来源: ADIS

摘要:

Genetronics Biomedical is using its electroporation therapy technology to deliver bleomycin to tumour cells for the treatment of cancer. Genetronics have developed the MedPulser®Electroporation Therapy System, which consists of an electrical pulse generator and disposable electrode applicators. The MedPulser®system enables the delivery of large molecules into cells by briefly applying an electric field to the cell. This causes a transient permeability in the cell's outer membrane characterised by the appearance of pores across the membrane. After the field is discontinued, the pores close, trapping the therapeutic molecules inside the target cells. Genetronics is using the MedPulser®System in conjunction with bleomycin, an antineoplastic antibiotic that binds to DNA causing strand scissions.Genetronics is seeking a licensing partner for the use of electroporation for the delivery of drugs in chemotherapy.In 1998, Genetronics entered a licensing and development agreement with Ethicon for electroporation and electrofusion. Under the terms of this agreement, Ethicon was to develop and clinically test the Genetronics electroporation delivery system and conduct all regulatory activities throughout the world except Canada. Ethicon would also market the products once regulatory approval has been obtained and Genetronics was to receive a percentage of the net sales and as license fees. However, in July 2000, Ethicon exercised its rights to terminate the agreement without cause. All rights were returned to Genetronics in January 2001.In 1997, Genetronics entered an agreement with Abbott Laboratories for the manufacture of bleomycin for use in the US in its MedPulsar®system after regulatory approval had been granted for its use in the treatment of solid tumours. In a separate supply agreement, Faulding Inc. has agreed to manufacture bleomycin for Genetronic for use in Canada after regulatory approval had been granted.The MedPulsar®Electroporation Therapy System with bleomycin is currently in phase III pivotal studies in the US as a treatment for recurrent and second primary squamous cell carcinomas of the head and neck. Genetronics received approval for the Electroporation Therapy system as a device in March 1999 when it achieved CE Mark certification.In February 2004, Genetronics announced that it had completed a Special Protocol Assessment review process with the US FDA for two new trials that will compare bleomycin electroporation therapy to surgery.[1]The primary endpoint will be tissue and function preservation rather than survival. One proposal is for recurrent head and neck cancer, and the other is for disfiguring cutaneous cancer. Three Institutional Review Boards in the US have approved the two protocols and Genetronics has initiated enrolment. In June 2004, Genetronics was granted fast-track status for its MedPulsar®Electroporation Therapy System clinical development programme for patients with head and neck cancer.[2]Shifting from a primary endpoint of survival to a quality-of-life outcome will enable those clinical trials to be carried out faster with less cost and with a higher likelihood of success. As a result, Genetronic's phase III trials focussing on survival as a primary endpoint have been discontinued. This includes a phase III trial for late-stage, recurrent head and neck cancer in combination with the normal standard of treatment compared with normal standard of treatment alone. Interim results from this trial had suggested bleomycin electroporation therapy demonstrated local tumour control and preservation of organ function, as well as non-inferiority when compared with surgery.[3]This trial was initiated in May 2002.In March 2004, Genetronics initiated a post-European regulatory approval clinical study in patients with primary or recurrent squamous cell carcinoma of the head and neck (SCCHN).[4]This study aims to enrol approximately 100 patients at 12–15 hospitals located in the UK, Germany, Italy, France, Austria and other western European countries. The study is designed to support the commercialisation of the MedPulser®Electroporation System in the EU. Prior clinical trials established the safety and performance of the MedPulser®System for the treatment of SCCHN, leading to approval for sale in the EU based on achieving the CE Mark. This study will document the clinical and pharmacoeconomic benefit in support of reimbursement approval throughout Western Europe, establish centres of excellence to facilitate early sales, create a reference and customer base for a projected European commercial launch in 2005, and generate safety and efficacy data to support marketing applications in the US.The bleomycin delivery system has completed phase IIB trials in the US, Canada and Europe in patients with squamous cell carcinoma of the head and neck who have failed conventional therapies. Phase II data were submitted to the FDA in the first quarter of 2002 and a phase III trial was launched in May 2002. The therapy is also being used in France in patients with cancers of the head and neck, liver (metastatic) and melanoma. A review of the data from these phase II trials was completed in April 2001.In June 2004, Genetronics was granted two US patents. US patent 6 748 265 covers its trans-surface drug and gene delivery technology and provides additional proprietary rights for an apparatus and method to deliver genes, drugs and other molecules through tissue surfaces. The second US patent, 6 746 441, pertains to the field ofex vivotherapies and covers the introduction of molecules into cells by electroporation, either in a continuous-flow or batch mode, with a variable electric field orientation.In July 2004, Genetronics received a US patent (no. 6 763 264) covering methods for thein vivodelivery of a recombinant expression vector (DNA) or a pharmaceutical agent into tissue cells, and a method for the therapeutic application of electroporation to a patient to introduce macromolecules.

ISSN:1174-5886    

出版商:ADIS    

年代:2004

数据来源: ADIS

摘要:

Ampligen®[polyI:polyC12U] is a mismatched double-stranded RNA that acts by inducing interferon production (immunomodulator) and by activating an intracellular enzyme (RNase-L) against viral RNA transcripts (antiviral). Ampligen®, currently under development by Hemispherx Biopharma in the US, acts on the immunological system through T-lymphocyte stimulation and is indicated for the treatment of chronic fatigue syndrome and acquired immunodeficiency deficiency syndrome (AIDS), as part of the combined therapy.Ampligen®is available for licensing worldwide.In February 2004, Fujisawa Deutschland GmbH, a subsidiary of Fujisawa Pharmaceutical Co., entered into an option agreement with Hemispherx Biopharma with the intent of becoming a distributor for Ampligen®for the potential treatment of chronic fatigue syndrome in Germany, Switzerland and Austria. An option fee of euro400 000 was paid pursuant to the terms of the option agreement and upon execution of the Distribution Agreement, Fujisawa will pay Hemispherx fees and milestone payments with a potential worth of several millions of dollars.[1]In September 2003, Hemispherx Biopharma Inc. entered into an agreement with Guangdong Medicine Group Corporation to organise clinical trials, marketing, sales and distribution for both of its lead compounds, Ampligen®and Alferon N®in the People's Republic of China. The agreement stipulates that the Guangdong Medicine Group Corporation (GMC) will conduct clinical trials with Ampligen®for the treatment of HIV. All costs related to the trials are to be covered by GMC. Additionally, GMC has to develop and implement marketing and promotional programmes.[2]In May 2003, Hemispherx Biopharma and the Center for Cell and Gene Therapy entered into a research project agreement that will see Ampligen®implemented in a protocol used in patients with relapsed EBV-positive Hodgkin's Lymphoma.[3]In March 2002, Esteve and Hemispherx Biopharma entered into a collaborative agreement under which Esteve will be the sole distributor of Ampligen®in Spain, Portugal and Andorra for the treatment of chronic fatigue syndrome. Under this agreement, in addition to other terms, Esteve will also collaborate in the drug product development by conducting clinical studies in Spain in patients coinfected with HIV/HCV.In July 2001 Hemispherx Biopharma announced that it had formed a strategic alliance with Empire Health Resources for clinical trials of Ampligen®in the treatment of HIV and hepatitis C virus infections. Empire Health Resources, a healthcare management firm, will be responsible for accrual and retention of patients for HIV trials, and protocols for trials in patients with hepatitis C or both HIV and hepatitis C infections.Hemispherx has entered into a collaboration with RED Laboratories, and RED Laboratories NV expects that this will facilitate the continued development of Ampligen®. Hemispherx has also entered into an agreement with Schering Plough to use a Schering facility as its principal manufacturing platform in the US. This agreement may be expanded to include other territories.Hemispherx and AOP Orphan Pharmaceuticals have signed a marketing agreement for Ampligen®for the treatment of chronic fatigue syndrome for Austria, the Czech Republic, Poland and Hungary.In an arrangement between Hemispherx and Bioclones, Bioclones has certain marketing rights for Ampligen®in the Southern Hemisphere, UK and Ireland.In the US, Ampligen®has been granted orphan drug status for the treatment of AIDS, renal cell carcinoma (phase II, completed), chronic fatigue syndrome (phase III) and invasive/metastatic malignant melanoma (phase II).In August 2004, Hemispherx announced that it intends to use the proceeds from the private placement of company stock to complete the clinical work for its immunotherapeutics/ antivirals Ampligen®and Oragens™.Previously, Hemispherx submitted an application to the EMEA for the approval of Ampligen®for the treatment of chronic fatigue syndrome; the first stage of the regulatory review has been cleared. In 2000, Hemispherx Europe (Hemispherx) obtained orphan drug status for Ampligen®for the treatment of chronic fatigue syndrome in the EU, providing Hemispherx with 10 years of marketing exclusivity following the launch of the drug, as well as potential financial research benefits for the agent.In February 2000, Crystaal Corporation (now Biovail Pharmaceuticals Canada) acquired exclusive marketing rights to Ampligen®in Canada, where it submitted an NDA for the agent for the treatment of chronic fatigue syndrome. In the meantime, Ampligen®has been available since May 1996 under the Canadian Emergency Drug Release Programme for the treatment of chronic fatigue syndrome and immune dysfunction syndrome by Rivex Pharma (Helix BioPharma).Bioclones has initiated clinical studies with Ampligen®for the treatment of chronic fatigue syndrome in Australia. The active substance for Ampligen®is manufactured by F.H. Faulding Ltd. Clinical treatment programmes for chronic fatigue syndrome in other Pacific Rim countries are planned. Ampligen®is available for severe chronic fatigue syndrome on a named patient, cost-recovery basis in South Africa.Hemispherx has developed a ‘ready-to-use’ liquid formulation of the drug and has begun treating patients with chronic fatigue syndrome in ongoing clinical trials. Hemispherx has also developed an oral version of the drug (Oragen®), which is undergoing preclinical evaluation.In February 2001, Hemispherx Biopharma announced that it was initiating phase II/III trials of Ampligen®in the treatment of late-stage, multidrug-resistant strains of HIV in the European Union. Patients treated in these studies will have exhausted all other treatment options.In July 2001, Hemispherx stated that Ampligen®was being evaluated in a phase IIb trial in patients with HIV in the US. The trial, comprising two studies, REARMI and REARMII (Research/Evaluation of Ampligen®for Retroviral Mutations I and II), will evaluate the ability of Ampligen®to prevent the emergence of mutated, drug-resistant strains of the virus. ‘Several hundred’ patients currently on antiretroviral therapy and at risk of viral relapse will be enrolled at centres in Connecticut, New York, Florida and California. A second phase IIb study evaluating the effect of Ampligen®on structured treatment interruptions (STI) is also underway. Final results from this study were reported in December 2002.NIH sponsored studies of potential therapies for SARS have identified Ampligen®as having unusually high and consistent antiviral activity against human coronavirus, the pathogen implicated as the causative agent of the disease. Ampligen®demonstrated very high potency at very low concentrations (0.4 µg/mL) and had a favourable safety profile.[4]In October 2003, Hemispherx announced that, based on these promsing new results, the company will stockpile injectible and/or oral formats of Ampligen®and Alferon N®.[5]Independent researchers have demonstrated the antiviral activity of Ampligen®against flaviviruses (West Nile virus, Equine Encephalitis virus, Dengue fever virus and Japanese Encephalitis virus) as well as virus classes associated with bioterrorism. In an animal study, Ampligen®was shown to prevent destruction of nerve cells, reduce virus concentrations in the brain and blood stream and increase survival rates.[6]Researchers at the Rega Institute in Belgium have published results from an animal study demonstrating that Ampligen®was superior at protecting mice against coxsackie B3 virus-induced myocarditis compared with pegylated interferon.[7]In May 2004 Hemispherx announced that it had filed an expanded US patent application covering the use of Ampligen®for the potential treatment and prevention of severe acute respiratory syndrome (SARS) and dreaded emerging viruses.

ISSN:1174-5886    

出版商:ADIS    

年代:2004

数据来源: ADIS

摘要:

Rubitecan [Orathecin™, 9-nitrocamptothecin, 9NC, RFS 2000] is a topoisomerase I inhibitor extracted from the bark and leaves of theCamptotheca acuminatatree, which is native to China. Rubitecan is an oral compound being developed for the treatment of pancreatic cancer and other solid tumours by SuperGen. One of the major benefits of rubitecan is that it can be administered in an outpatient setting, so patients can be treated in their homes.Rubitecan was isolated by the Stehlin Foundation in the US. SuperGen is currently awaiting regulatory approval in the US and the EU for rubitecan in the treatment of pancreatic cancer.At the BIO-2004 conference, SuperGen announced it is seeking a partner for rubitecan for territories outside the US.SuperGen acquired exclusive worldwide rights to rubitecan from the Stehlin Foundation in 1997 except in Mexico, Canada, Spain, Japan, the UK, France, Italy and Germany. SuperGen has also received approval from the US FDA to use its own manufactured rubitecan in clinical trials. SuperGen and the Stehlin Foundation have an 8-year research agreement that secures global rights to other camptothecins and additional anticancer compounds for the former.In December 1999, SuperGen and Abbott signed a worldwide sales and marketing agreement for rubitecan. Under the terms of the agreement, Abbott had exclusive distribution and promotion rights for rubitecan outside the US, and co-promotion rights with SuperGen within the US. In return, Abbott made an initial equity investment in SuperGen. SuperGen and Abbott Laboratories ended their collaboration agreement in February 2002 by mutual consent with SuperGen stating that the dissolution of the agreement was based on commercial motivation rather than anything to do with rubitecan's safety or efficacy. Abbott no longer has rights or obligations to purchase shares of SuperGen stock or an option to purchase up to 49% of the company. For its part, SuperGen will no longer receive milestone payments worth up to $US57 million.SuperGen has formed a clinical and business alliance with US Oncology (created by the merger between American Oncology Resources and Physician Reliance Network in the US), and will collaborate on clinical trials of rubitecan. SuperGen believes that this relationship will increase the patient population available for trials and enable it to market the drug directly to Oncologists.SuperGen and Capital Research and Management Company have completed a $US16.6 million private placement transaction that will enable future funding for the rubitecan programme as well as other oncology programmes.In July 2004, SuperGen's European subsidiary, EuroGen Pharmaceuticals, submitted a Marketing Authorisation Application for rubitecan in the treatment of pancreatic cancer.[1]The application will be reviewed under the EMEA Centralised Procedure.In June 2003, the EMEA granted SuperGen orphan drug status for rubitecan for the treatment of pancreatic cancer.[2]The US FDA has also granted orphan drug status for rubitecan in the treatment of pancreatic cancer and fast-track status for rubitecan for the treatment of locally advanced or metastatic pancreatic cancer that is resistant or refractory to chemotherapy.SuperGen has conducted three phase III pivotal trials in patients with pancreatic cancer. A phase III randomised trial in chemotherapy-naive patients was conducted at 132 centres throughout the US. The trial enrolled approximately 994 patients who were randomised to receive rubitecan or gemcitabine. Enrolment was completed in October 2001.Another phase III trial has compared rubitecan with the most appropriate chemotherapy in chemotherapy-resistant patients. Enrolment of over 400 patients at 200 medical centres across the US was completed in June 2001. Results from the trial were presented at the 39th Annual Meeting of the American Society of Clinical Oncology (ASCO-2003) [Chicago, US; 31 May – 3 June 2003], after they had been compiled, analysed and submitted to the FDA. The results of the study showed that rubitecan could not help all chemotherapy-resistant patients, but could increase survival in those that do respond.[3,4]The other phase III pivotal trial was conducted in patients with pancreatic cancer who had failed treatment with gemcitabine. This trial completed enrolment in October 2001, and had enrolled approximately 448 patients.SuperGen is conducting phase II trials of rubitecan in patients with solid tumours in the UK, Italy, France, Germany, the Netherlands and Denmark. Each trial will enrol 100–150 patients with various tumour types, including colorectal, lung, breast, gastric, prostate, cervical and head and neck cancers. Phase I/II trials are underway to investigate rubitecan as a radiosensitiser in patients with lung cancer, and phase II trials in patients with breast cancer are also being conducted. A phase II study in ovarian cancer patients is also being conducted. Results from an ongoing phase II study in cancer patients have shown that rubitecan was effective against chordomas, a rare type of bone cancer.Phase II studies are also underway in haematological malignancies including myelodysplastic syndrome (preleukaemia) and chronic myelomonocytic leukaemia.In February 2000, SuperGen announced that its IND submission for rubitecan had been approved by the Therapeutics Products Programme of Canada. The company stated that it intended to begin clinical trials in Canada in the near future.In February 2004, SuperGen announced an offering of shares of its common stock to finance the commercialisation of rubitecan capsules.In July 2003, SuperGen was granted a US patent covering combination therapies with chemotherapeutic anthracycline agents and structural modifications that may one day lead to next-generation rubitecan compounds.[5]In December 2002, SuperGen was granted US patent No. 6 482 830, covering its polymorphic formulations of rubitecan. The patent also covers a class of polymorphs that are similar to the one at the centre of rubitecan. In addition, SuperGen was also issued US patent No. 6 485 514 in December 2002, covering the local delivery of rubitecan via stents and/or catheters to sites of proliferating cells. Stent- or catheter-delivered rubitecan may be beneficial in certain types of cardiac procedures, such as ablation or angioplasty, as well as for direct injection into a certain number of solid tumours.SuperGen is also developing an inhaled, liposomal formulation of rubitecan. It acquired the worldwide rights to this formulation from the Clayton Foundation in December 1999. Inhaled rubitecan is in clinical trials in the US for the treatment of lung cancer and pulmonary metastatic cancer.

ISSN:1174-5886    

出版商:ADIS    

年代:2004

数据来源: ADIS