摘要:

Cataract formation represents a serious problem in the elderly, with approximately 25% of the population aged >65 years and about 50% aged >80 years experiencing a serious loss of vision as a result of this condition. Not only do cataracts diminish quality of life, they also impose a severe strain on global healthcare budgets. In the US, 43% of all visits to ophthalmologists by Medicare patients are associated with cataract. Surgery represents the standard treatment of this condition, and 1.35 million cataract operations are performed annually in the US, costing $US3.5 billion (year of costing, 1998).Unfortunately, the costs of surgical treatment and the fact that the number of patients exceeds surgical capacities result in many patients being blinded by cataracts worldwide. This situation is particularly serious in developing countries; worldwide 17 million people are blind because of cataract formation, and the problem will grow in parallel with aging of the population. In any event, surgical removal of cataracts may not represent the optimal solution. Although generally recognised as being one of the safest operations, there is a significant complication rate associated with this surgical procedure. Opacification of the posterior lens capsule occurs in 30–50% of patients within 2 years of cataract removal and requires laser treatment, a further 0.8% experience retinal detachments, approximately 1% are rehospitalised for corneal problems, and about 0.1% develop endophthalmitis. Although the risks are small, the large number of procedures performed means that 26 000 individuals develop serious complications as a result of cataract surgery annually in the US alone. Thus, risk and cost factors drive the investigation of pharmaceutical approaches to the maintenance of lens transparency.The role of free radical-induced lipid oxidation in the development of cataracts has been identified. Initial stages of cataract are characterised by the accumulation of primary (diene conjugates, cetodienes) lipid peroxidation (LPO) products, while in later stages there is a prevalence of LPO fluorescent end-products. A reliable increase in oxiproducts of fatty acyl content of lenticular lipids was shown by a direct gas chromatography technique producing fatty acid fluorine-substituted derivatives. The lens opacity degree correlates with the level of the LPO fluorescent end-product accumulation in its tissue, accompanied by sulfhydryl group oxidation of lens proteins due to a decrease of reduced glutathione concentration in the lens. The injection of LPO products into the vitreous has been shown to induce cataract. It is concluded that peroxide damage of the lens fibre membranes may be the initial cause of cataract development.N-acetylcarnosine (as the ophthalmic drug Can-C™), has been found to be suitable for the nonsurgical prevention and treatment of age-related cataracts. This molecule protects the crystalline lens from oxidative stress-induced damage, and in a recent clinical trial it was shown to produce an effective, safe and long-term improvement in sight. When administered topically to the eye in the form of Can-C™,N-acetylcarnosine functions as a time-release prodrug form of L-carnosine resistant to hydrolysis with carnosinase.N-acetylcarnosine has potential as anin vivouniversal antioxidant because of its ability to protect against oxidative stress in the lipid phase of biological cellular membranes and in the aqueous environment by a gradual intraocular turnover into L-carnosine.In our study the clinical effects of a topical solution ofN-acetylcarnosine (Can-C™) on lens opacities were examined in patients with cataracts and in canines with age-related cataracts. These data showed thatN-acetylcarnosine is effective in the management of age-related cataract reversal and prevention both in human and in canine eyes.

ISSN:1174-5886    

出版商:ADIS    

年代:2004

数据来源: ADIS

摘要:

Objective and designITF-1697 is a chemically modified LYS-Pro tetrapeptide that corresponds to sequence 113-116 of C-reactive protein. Previous studies have demonstrated significant anti-ischaemic and antithrombotic activity of this tetrapeptide. The aim of this prospective, randomised, double-blind study in patients with acute myocardial infarction undergoing coronary revascularisation was to investigate the safety and efficacy of prolonged intravenous (IV) infusion of ITF-1697 at different doses on reduction of infarct size, as assessed by radionuclide imaging.Patients and methodsInjection of technetium-99m (Tc99m) was followed by injection of ITF-1697 or placebo bolus and 24-hour infusion in patients with acute myocardial infarction. Percutaneous transluminal coronary angioplasty (PTCA) was performed and succeeded by radionuclide imaging. A second Tc99m injection and radionuclide imaging was performed 7 days after the PTCA or at hospital discharge. The primary efficacy variable was set as the ratio between the myocardial salvage (size of the initial perfusion defect minus the final size of the infarct) and the initial area at risk (myocardial salvage index). Twenty-three patients were included in the study protocol, of whom nine were randomised to the ITF-1967 dose 1 group (loading dose 55 μg/kg IV, infusion 0.5 μg/kg/min for 24 hours), a further nine to the ITF-1697 dose 2 group (loading dose 110 μg/kg IV, infusion 1.0 μg/kg/min for 24 hours), and the remaining five to the placebo group.ResultsThe defined safety variables (adverse events, laboratory parameters, vital signs and clinical outcome) exhibited no relationship to the application of ITF-1697. Comparison of myocardial salvage index revealed no statistical difference within the three groups (p = 0.65). Hypothesis testing on the myocardial salvage as well as the empirical and bias-correct confidence intervals (CIs) revealed significant differences between the ITF-1697 dose 2 group and the placebo group (95% CI 2.75, 18.07).ConclusionThe application of the tetrapeptide ITF-1697 during acute myocardial infarction to reduce infarct size was found to be feasible and safe in this pilot trial.

ISSN:1174-5886    

出版商:ADIS    

年代:2004

数据来源: ADIS

摘要:

ABI 007 [Abraxane™] is an albumin-stabilised nanoparticle formulation of paclitaxel designed to overcome insolubility problems encountered with paclitaxel. This then eliminates the need for toxic solvents like cremophor, which limits the dose of paclitaxel that can be administered and hence affect overall drug efficacy. Studies have shown that the albumin receptor-mediated paclitaxel-transport mechanism is analogous to the opening of a ‘trapdoor’ on the endothelial cell wall within blood vessels. This facilitates the passage of ABI 007 from the bloodstream via the blood vessels to the underlying tumour tissue.[1]ABI 007 is being developed for the treatment of a variety of tumour types by American Pharmaceutical Partners. In addition to the standard infusion formulation of ABI 007, oral and pulmonary delivery formulations are also being investigated.American Pharmaceutical Partners, a subsidiary of American BioScience, secured exclusive North American marketing and manufacturing rights to ABI 007 from American BioScience in November 2001.In anticipation of product launch within the fourth quarter of 2004, the company formed Abraxis Oncology and recruited an experienced sales and marketing team. The company has also accumulated approximately $US28 million of paclitaxel inventory. As such, American Pharmaceutical Partners anticipates pre-launch expenses to cost approximately $US40 million, incurred over 2004. In addition, the company expects to make two milestone payments worth $US10 million as well as $US15 million, based upon US FDA acceptance of NDA filing in the second quarter of 2004 and subsequent US FDA approval, respectively. The milestone for US FDA approval would be capitalised and amortised over the estimated life of the product.[2]Previously, American Pharmaceutical Partners reported that its rolling NDA submission for ABI 007 commenced in May 2003. In July 2003, the company announced that this was progressing on schedule and expected to have completed its entire NDA submission by the end of 2003. The company also began preparations to form a sales and marketing group in anticipation of product launch. In addition, production of commercial quantities of ABI 007 was expected to begin in the second half of 2003. The US FDA granted fast-track status to ABI 007 for this indication in January 2003.[3]The decision for NDA filing was based on the successful completion of a phase III trial evaluating ABI 007 versus standard paclitaxel among 460 patients with metastatic breast cancer in the US.[4,5]In September 2003, American Pharmaceutical Partners and American BioScience jointly announced positive interim results from the trial, which shows that the primary efficacy objective had been exceeded.[6]American BioScience completed this phase III trial in early 2003 with the results unblinded in mid-2003. The phase III study directly compared the efficacy of ABI 007 260 mg/m2versus paclitaxel 175 mg/m2. Both agents were administered every 3 weeks. ABI 007 was administered as a 30-minute infusion without steroid pretreatment. Paclitaxel-treated patients received steroid pretreatment and the drug was administered over 3 hours. Enrolment was completed in December 2002 with 460 first- and second-line metastatic breast cancer patients enrolled. A Data Monitoring Committee concluded in October 2002 that a sample-size adjustment of the phase III trial was not required and that the study could be continued to completion.A phase II trial of ABI 007 was also underway in metastatic breast cancer patients who have failed taxane therapy. The trial was evaluating a weekly rather than 3-weekly regimen of ABI 007.Also in February 2004, American BioScience initiated a multicentre phase II trial in patients with metastatic melanoma. The trial will evaluate both chemotherapy-naive patients (at a dose of 150 mg/m2administered weekly) and patients who have previously received chemotherapy (at a dose of 100 mg/m2administered weekly) as treatment for metastatic disease.[7]In May 2003, American Pharmaceutical Partners reported that ABI 007 is also being evaluated for the treatment of non-small cell lung cancer, ovarian cancer, melanoma and cervical cancers. Phase I/II trials have also been conducted in other solid tumours, including squamous cell cancer of the head and neck, and pelvis. Phase I trials have also been conducted in patients with solid tumours to evaluate the administration of ABI 007 on a weekly schedule.In September 2003, American BioScience was issued US patent No. 6 506 405, which has 89 claims covering compositions of matter and unit dosage forms. In addition, the patent covers methods of use without the requirement for pretreatment with steroid therapy or growth factor support.In July 2003, the US Court of Appeals for the Federal Circuit in Washington DC unanimously ruled that American BioScience is the true and rightful owner of patent No. 5 780 653. This patent covers three next-generation taxane anticancer compounds. This ruling overturned a lower court decision in a lawsuit brought in 1998 by Florida State University (FSU) and FSU Prof. Robert Holton's privately held company, Taxolog. In the lawsuit, FSU and Taxolog alleged that Prof. Holton and others at FSU were the true inventors of the compounds claimed under American BioScience's patent.

ISSN:1174-5886    

出版商:ADIS    

年代:2004

数据来源: ADIS

摘要:

Gilead Sciences is developing a fixed-dose co-formulation of two of its reverse transcriptase inhibitors, emtricitabine [Emtriva™] and tenofovir disoproxil fumarate [Viread®], for once-daily dosing in combination with other antiretrovirals for the treatment of HIV infection. Each co-formulated tablet will contain 300mg of tenofovir disoproxil fumarate and 200mg of emtricitabine.Emtricitabine [Emtriva™] is a nucleoside reverse transcriptase inhibitor (NRTI) with demonstrated potent activity against HIV and hepatitis B virus (HBV). It was first approved in the US by the FDA in July 2003 and is indicated for adults aged ≥18 years. Safety and effectiveness in paediatric patients have not been established. In antiretroviral-treatment-experienced patients, the use of emtricitabine may be considered for adults with HIV strains that are expected to be susceptible to the drug as assessed by genotypic or phenotypic testing. The recommended dose of emtricitabine is one 200mg capsule daily, with or without food.In the European Union, emtricitabine is indicated in combination with other antiretroviral agents for the treatment of HIV in adults and children, where it is also licensed as an oral 10 mg/mL solution. The oral solution is for use in infants older than 4 months, children and patients unable to swallow hard capsules, and patients with renal impairment who require dose reduction.Tenofovir disoproxil fumarate [Viread®] is a nucleotide reverse transcriptase inhibitor that is indicated in combination with other antiretroviral agents for the treatment of HIV-1 infection in treatment-experienced patients. The drug was first approved in the US in October 2001, followed by further approvals in the European Union, Australia, Iceland, Brazil, Canada and Switzerland. The drug has been launched in all these countries. In February 2003, the EMEA's advisory committee adopted a positive opinion to extend the indication of tenofovir disoproxil fumarate in all 15 member states to include the product's use in antiretroviral-naïve HIV-infected patients.In July 2003, Japan Tobacco signed an agreement with Gilead for the commercialisation of tenofovir disoproxil fumarate and emtricitabine and the future co-formulation of these two drugs within Japan. Under the terms of the agreement, Japan Tobacco will be submitting an application to the Japanese Ministry of Health, Labour and Welfare for regulatory approval of tenofovir disoproxil fumarate and emtricitabine.On 15 March 2004, Gilead announced the submission of a New Drug Application (NDA) to the US FDA and a Marketing Authorisation Application (MAA) to the EMEA for marketing approval of the fixed-dose co-formulation of emtricitabine and tenofovir disoproxil fumarate. The MAA will be reviewed under the centralised procedure, which, when finalised, will provide one marketing authorisation in all 25 member states of the enlarged European Union.[1]Gilead anticipates launching the combination pill on the US market early in 2005. Regulatory filings for marketing approval in Japan by Japan Tobacco are also expected during 2004.In August 2003, Gilead announced that enrolment had begun in a 48-week phase III study (Study 934) evaluating the efficacy of a once-daily regimen of Viread®and Emtriva™ versus Combivir®. The open-label, multicentre trial will enrol up to 500 treatment-naive, HIV-infected patients in the US and Europe. Patients in one arm will receive Viread®300mg, Emtriva™ 200mg and efavirenz 600mg once daily. Patients in the comparator arm will receive Combivir®(lamivudine 150mg/zidovudine 300mg) twice daily and efavirenz 600mg once daily.[2]

ISSN:1174-5886    

出版商:ADIS    

年代:2004

数据来源: ADIS

摘要:

In November 1998, Novartis Pharma of Switzerland and SkyePharma PLC of the UK signed an agreement to jointly develop a new formulation of the β2-adrenoceptor agonist formoterol (Foradil®). The new product, Foradil®Certihaler™, utilises a multidose dry-powder inhaler (MDPI or MDDPI) device, SkyeHaler™, developed by SkyePharma. It also utilises SkyePharma's SkyeProtect™ powder formulation technology, which protects the drug from moisture. The product is waiting for approval for the treatment of asthma. Foradil®MDPI may also have potential for the treatment of chronic obstructive pulmonary disease (COPD).Novartis has stated that Foradil®Certihaler™ offers certainty of dosing and dose confirmation, and will also contain a dose counter that indicates the number of doses left.SkyePharma is responsible for development of the product in its finished form; this includes the supply of both the powder and the inhalation device as a product to Novartis. The product is manufactured at SkyePharma's Lyon facility in France. SkyePharma is receiving fees, development costs and milestone payments from Novartis. SkyePharma will also receive royalty income on worldwide sales. SkyePharma has granted Novartis an exclusive worldwide licence to market Foradil®MDPI.Foradil®Certihaler™ was approved in Switzerland in March 2004. This is the first approval in Europe, and will trigger an undisclosed milestone payment by Novartis to SkyePharma.[1]Submissions for regulatory approval in the asthma indication were filed in the EU (on a country-by-country basis) and the US in December 2002. On 22 October 2003, SkyePharma announced that the US FDA had issued an ‘approvable’ letter for Foradil®Certihaler™.[2] Launch of the product is anticipated for 2004.Clinical trials of Foradil®MDPI for the treatment of asthma began in October 1999. In December 2000, phase III trials commenced in Europe. SkyePharma stated in April 2001 that phase III trials had commenced recently in the US.SkyePharma estimated in April 2001 that the worldwide sales potential of Foradil®MDPI could be as much as $US600 million. SkyePharma anticipates receiving royalties and manufacturing revenues of more than 10%.

ISSN:1174-5886    

出版商:ADIS    

年代:2004

数据来源: ADIS

摘要:

Idraparinux sodium [SANORG 34006,SR 34006], a synthetic, anti Xa pentasaccharide and analogue of SR 32701 and fondaparinux sodium, was in development with Sanofi (now Sanofi-Synthélabo) and Organon (Akzo Nobel) in Europe and the USA (now Sanofi-Synthélabo alone). It may have potential in the treatment and secondary prevention of thrombosis, especially deep-vein thrombosis (DVT). Because of the long duration of action of idraparinux sodium, it may be suitable for once-weekly administration.In January 2004, Sanofi-Synthélabo announced it was to acquire, before the end of the first quarter 2004, all the rights of Organon relating to idraparinux sodium, subject to approval of the regulatory authorities. Sanofi-Synthélabo is to make payments to Organon based on future sales.[1]Idraparinux sodium has completed phase IIb development with the PERSIST study and it is in phase III clinical trials. In June 2003, Organon announced the initiation of pivotal phase III studies as a once-weekly treatment of DVT and pulmonary embolism (PE), and for the prevention of stroke in patients with atrial fibrillation. The AMADEUS study will focus on patients with atrial fibrillation while the Van Gogh PE, Van Gogh DVT and the Van Gogh extension (EXT) will focus on patients with DVT or PE.[2]

ISSN:1174-5886    

出版商:ADIS    

年代:2004

数据来源: ADIS

摘要:

Nektar Therapeutics (formerly Inhale Therapeutic Systems) has developed a pulmonary drug delivery system for insulin [HMR 4006, Exubera®].The rationale behind developing a pulmonary drug delivery system is to ensure that insulin powder is delivered deep into the lungs, where it is easily absorbed into the bloodstream, in a hand-held inhalation device. The device converts the insulin powder particles into an aerosol cloud for the patient to inhale. No propellants are used. The inhaler requires no power source and the clear chamber ensures that the patient knows immediately when all the insulin has been inhaled.Nektar Therapeutics, developers of the inhalation device and formulation process, has licensed the system to Pfizer. Under the terms of the agreement, Pfizer will lead the clinical development of inhaled insulin, while working with Nektar Therapeutics to develop the technology required for packaging the product.Pfizer has an agreement with Hoechst Marion Roussel (now Aventis Pharma) for developing, manufacturing and promoting inhaled insulin. Under the terms of the collaboration, Aventis Pharma will supply recombinant insulin to Nektar Therapeutics to process it into dry powder for incorporation into the inhaler device. Nektar Therapeutics will receive royalties on sales of inhaled insulin marketed by Pfizer and Aventis Pharma, and milestone payments and research support from Pfizer. Aventis Pharma's codename for the product is HMR 4006.Profil, a CRO in Germany, is cooperating with Pfizer/Aventis Pharma in the development of inhaled insulin.In March 2004, Pfizer and Aventis announced that the European Medicines Evaluation Agency (EMEA) accepted the filing of the MAA for inhaled insulin (Exubera®) for the treatment of type 1 and type 2 diabetes mellitus. The two companies are working with the US FDA to determine the timing for the submission of the NDA in the US.[1]Pfizer completed five pivotal phase III clinical trials with inhaled insulin in patients with type 1 and type 2 diabetes mellitus in 120 centres worldwide, and will use a fourth prototype inhaler device that is half the size of the first prototype, and has reduced manufacturing costs.Pfizer and its partner, Aventis Pharma, are conducting additional long-term pulmonary safety data studies in patients with type 1 and type 2 diabetes.[2]Pfizer is also conducting phase III clinical trials with inhaled insulin in paediatric patients aged 6–17 years.Nektar Therapeutics is using its Advanced PEGylation technology to develop a dry powder-inhaled polyethylene glycol (PEG) formulation for delivering peptides efficiently across the lungs and to promote prolonged serum concentration of the peptide. PEG is a neutral, water-soluble, nontoxic polymer comprising any number of repeating units of ethylene oxide. PEGylation is designed to increase the size of the active molecule and ultimately improve drug performance by optimising pharmacokinetics, increasing bioavailability, and decreasing immunogenicity and dosing frequency.The investigation has begun with inhaled, long-acting (PEGylated) insulin [inhaled PEG-insulin, PEGylated insulin – Nektar], and is funded by Pfizer.Preclinical results of a dry powder formulation of inhaled PEG-insulin presented at the 63rd Scientific Sessions of the American Diabetes Association (ADA-2003) [June 2003, New Orleans, LA, USA] demonstrated prolonged systemic activity of insulin in dogs.[3]Nektar Therapeutics was granted US patent 5 997 848 on a method for delivering inhalable insulin. The patent covers a method for delivering of 0.5–15mg of aerosol dry powder insulin per dosing session in 1–4 individual dosages into the deep lung for systemic absorption. The patent does not specify the formulation of insulin or aerosol delivery device.Nektar Therapeutics estimated in June 2002 that Exubera®could earn the company potential revenues of >$US200 million.

ISSN:1174-5886    

出版商:ADIS    

年代:2004

数据来源: ADIS

摘要:

Oxipurinol [alloxanthine, Oxyprim™, oxypurinol] is the active metabolite of the only commercially available xanthine oxidase inhibitor, allopurinol. Oxipurinol is also a xanthine oxidase inhibitor. Oxipurinol is currently being developed by Cardiome Pharma. It is waiting for approval in the US for the treatment of allopurinol-intolerant hyperuricaemia (gout) and is in phase III trials for the treatment of congestive heart failure.Allopurinol is indicated for the treatment of symptomatic hyperuricaemia, or gout. Approximately 3–5% of patients receiving allopurinol develop intolerance to the drug. Oxipurinol was originally developed by Burroughs Wellcome (later GlaxoSmithKline), and has been available on a compassionate-use basis since 1967 for use in allopurinol-intolerant patients. The licensee company ILEX Oncology has stated that oxipurinol does not have patent protection.Oxipurinol's potential for treatment of congestive heart failure is based on the possibility that xanthine oxidase inhibitors may improve myocardial work efficiency by sensitising cardiac muscle cells to calcium ions, which are a key determinant of cardiac muscle function. This results in more efficient contraction of cardiac muscle cells, without the same increase in oxygen demand.At the second annual BioPartnering North America conference (BPN-2004) [February 2004, Vancouver, Canada], Cardiome Pharma stated that it was seeking a commercialisation partner to market and distribute oxipurinol in the US for the treatment of allopurinol-intolerant hyperuricaemia.In 1995, ILEX Oncology obtained an exclusive licence to oxipurinol from Burroughs Wellcome. Burroughs Wellcome later became part of Glaxo Wellcome, which merged with SmithKline Beecham in December 2000 to form GlaxoSmithKline. ILEX's licence agreement is now with GlaxoSmithKline and The Wellcome Foundation.In December 2001, ILEX granted Paralex, a privately held New York-based company, an exclusive sublicence to all of ILEX's rights to oxipurinol for the treatment of hyperuricaemia in allopurinol-intolerant patients. Paralex additionally gained the right to develop and commercialise oxipurinol in all fields, under data and technology owned by ILEX. Furthermore, Paralex had licensed certain intellectual property rights from The John Hopkins University relating to cardiovascular applications of xanthine oxidase inhibitors. Paralex was acquired by Cardiome Pharma in March 2002.Cardiome Pharma announced early in May 2002 that it had exercised its option to acquire from ILEX Oncology Inc. rights to clinical trial data for oxypurinol for the treatment of gout in allopurinol-intolerant patients. ILEX completed its open-label phase II clinical study of Oxyprim™ in allopurinol-intolerant gout patients, and the trial data were transferred to Cardiome. Cardiome stated in May 2002 that it intended to commence a further phase II trial of oxypurinol in gout. Phase III trials were in progress in 2003 in this indication.In 1995, ILEX Oncology continued the compassionate use distribution of oxipurinol while establishing a US FDA-approved registration plan for the agent. In November 1998, ILEX received Orphan Drug status for the use of oxipurinol in patients with symptomatic hyperuricaemia. ILEX Oncology's Development Pipeline for 1998 stated that oxipurinol had entered phase II clinical trials for the treatment of hyperuricaemia. In 2001, the clinical trials listing service CenterWatch stated that oxipurinol was in a phase II clinical trial with ILEX Oncology for the treatment of symptomatic hyperuricaemia in patients who are intolerant to allopurinol. The trial appeared to be taking place in the US, and was a multicentre, open-label, 14-week study in 90 patients.In February 2003, Cardiome confirmed beginning patient enrolment in three smaller phase II studies, with the first trial (EXOTIC) now completed. These three smaller proof-of-concept studies will observe surrogate endpoints such as cardiac output and exercise tolerance. The second proof-of-concept study in patients with CHF of ischemic aetiology (IV), known as EXOTIC-EF (Evaluation of XanThine Oxidase Inhibition on Cardiac Ejection Fraction), will assess the effects of oxypurinol on left ventricular performance. The EXOTIC-EF trial will start in the first quarter of 2004 and be completed by the second quarter of 2004.The third, LA PLATA, proof-of-concept study will explore the effects of 1 month of oral oxypurinol therapy on exercise capacity and left ventricular performance. It is projected that the LA PLATA study will start in the first quarter of 2004 and be completed by the third quarter of 2004.During the Heart Failure Society of America's meeting on 21 September 2003, Cardiome presented clinical data from its first proof-of-concept EXOTIC (European Xanthine Oxidase Inhibitors Trial In Cardiac Disease) study. Cardiome intends to conduct a second trial, at the Eppendorf Clinic at the University of Hamburg, to determine the effect of oxypurinol on left ventricular performance in patients with CHF of ischaemic aetiology. This study will be an extension of the original proof-of-concept study.[1]According to the 1st Annual BioPartnering conference held in Vancouver, Canada, in February 2003, Cardiome is seeking co-development partners for oxipurinol in the treatment of congestive heart failure.In July 2003, the US Patent and Trademark Office issued a new patent providing additional protection to Cardiome′s programme focused on treatment of congestive heart failure with oxypurinol. The patent, No. 6,569,862, was the second issued to the Johns Hopkins University (JHU) in this field. The key claims in the new patent cover use of the entire family of drugs known as xanthine oxidase inhibitors applied to contractile disorders of the heart, including congestive heart failure. An earlier patent issued to JHU contained provisions relating to a specific mechanism of action and to specific forms of heart disease. Both patents and related intellectual property are licensed exclusively to Cardiome.[2]

ISSN:1174-5886    

出版商:ADIS    

年代:2004

数据来源: ADIS

摘要:

Roflumilast [APTA 2217, B9302-107, BY 217, BYK 20869] is a selective phosphodiesterase IV inhibitor. It is being developed by Altana Pharma (formerly Byk Gulden), a subsidiary of Altana Group, as an orally administered therapy for asthma, chronic obstructive pulmonary disease (COPD), allergic rhinitis and psoriasis. The drug is awaiting regulatory approval in Europe for the treatment of asthma and COPD.Byk Gulden has stated that roflumilast relieves asthma symptoms through both an anti-inflammatory effect and a muscle relaxant effect. Roflumilast has potential as first-line long-term therapy in mild-to-moderate COPD and as additive long-term therapy in moderate-to-severe COPD. Altana has stated that roflumilast is to be marketed under the brand name Daxas®.Altana Group and Pharmacia Corporation (now Pfizer) signed an agreement on 22 April 2002 to collaborate on the development and commercialisation of roflumilast for the treatment of respiratory disorders, including asthma and COPD.[1]The companies will jointly develop the drug for the US, Europe and other markets. Pharmacia will co-ordinate development in the US and Altana will co-ordinate development in Europe. After approval of the drug, Pharmacia and Altana will jointly launch and promote roflumilast in the US, Europe and elsewhere. Altana will receive an upfront payment and additional milestone payments. Altana additionally has the option to co-promote Pharmacia products in the US and elsewhere. On 16 April 2003, Pharmacia Corporation was acquired by, and merged into, Pfizer.In November 2002, Altana and Tanabe Seiyaku signed an agreement to collaborate on the development and commercialisation of roflumilast for the treatment of respiratory diseases, including asthma and COPD. Tanabe Seiyaku and Altana will develop roflumilast for asthma and COPD in Japan, and will jointly launch and co-promote roflumilast in Japan following regulatory approval.[2]Roflumilast has been in multinational phase III clinical studies in Europe for the treatment of asthma and COPD. In September 2003, Altana announced the completion of a phase III trial in COPD in more than 1400 patients; the trial showed positive results.[3]In the US, roflumilast is in phase III trials for the treatment of asthma and phase II trials for the treatment of COPD. Phase I clinical trials of roflumilast were begun in Japan by Tanabe Seiyaku in the fourth quarter of 2003.Altana has stated that roflumilast has shown significant superiority over placebo in the treatment of asthma in phase II trials. The efficacy of the drug appears to be comparable to low-dose inhaled corticosteroids in the treatment of asthma and at least equal to inhaled corticosteroids in the treatment of COPD. Altana Group presented data from phase II trials in 516 patients with COPD at an analyst meeting [August 2001, Bad Homburg, Germany] that showed that roflumilast 500 µg/day significantly improved FEV1at 24 weeks compared with placebo.In March 2004, Altana Pharma presented pharmacokinetic data from a phase I trial of roflumilast at the 60th Annual Meeting of the American Academy of Allergy, Asthma and Immunology (AAAAI-2004) [San Francisco, CA, USA]. This open-label, randomised, two-period crossover study investigated the pharmacokinetics of oral roflumilast and its active metabolite, roflumilast N-oxide, among 12 healthy male subjects. Participants received single doses of oral roflumilast 500µg and intravenous (IV) roflumilast 150µg as a 15-min short-term infusion.[4]In November 2002, the combined global market for asthma and COPD products was estimated to be worth >$US11 billion. In Japan, products in this market segment reached sales of approximately $US1.5 billion in 2001. Roflumilast has patent protection in Europe and Japan until 2014 and in the US until 2015.TheFinancial Timesin April 2002 claimed that roflumilast is an ‘important’ product for Altana, due to be listed on the New York Stock Exchange later in the same month. The Altana chairman confirmed that the company had been in talks with Pfizer, Bristol-Myers Squibb and Novartis with regard to future development and commercialisation of roflumilast.In September 2002,Dow Jones Newswiresstated that Altana is to file for European approval of roflumilast 1 year later than initially was expected; however, this has not changed the company's outlook for the product, which was said to remain at at EUR1 billion.In August 2001, theFinancial Timesreported that roflumilast, for the indication of smoker's cough alone, has the potential to reach sales of more than $US500 million a year. A future co-marketing deal for roflumilast in the US was said to be “a key step towards expanding Altana's presence in the US”.

ISSN:1174-5886    

出版商:ADIS    

年代:2004

数据来源: ADIS

摘要:

Biovail Corporation has developed an orally delivered, once-daily, extended-release (ER) version of tramadol hydrochloride (Ralivia™) for the treatment of moderate to moderately severe pain. Tramadol (ER) uses Biovail's Smartcoat Technology to gain a graduated release of the active drug from the tablet.The company is also developing an orally disintegrating Flashtab (FlashDose®) version of the immediate-release (IR) tramadol hydrochloride.Biovail successfully completed two phase III, double-blind studies with tramadol ER (once-a-day) in patients with moderate to moderately severe pain.Two additional studies were initiated with tramadol ER to support the NDA filing that was submitted to the US FDA in December 2003 and accepted for review in February 2004.[1]Biovail is developing an orally disintegrating tablet version of tramadol (Ralivia™ FlashDose®) for the treatment of moderate to moderately severe pain. In March 2004, an NDA was submitted to the US FDA for this indication.[2]In June 2002, Biovail estimated tramadol's total market size to be $US11.3 billion, with a growth rate of 21%. In 2001, branded tramadol reached sales of $US662 million, according to Biovail – this excludes Ultracet®products (combination of tramadol/acetaminophen).

ISSN:1174-5886    

出版商:ADIS    

年代:2004

数据来源: ADIS