Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011860 (type 2 diabetes)
 57,723 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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. 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. 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. Nektar Therapeutics was granted US patent 5,997,848 on a method for delivering inhalable insulin. The patent covers a method for delivering of 0.5-15 mg 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 >200 million US dollars.
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PMID:Insulin inhalation--Pfizer/Nektar Therapeutics: HMR 4006, inhaled PEG-insulin--Nektar, PEGylated insulin--Nektar. 1513 80

Vascular reactivity to nitric oxide (NO) is mediated by NO-sensitive soluble guanylyl cyclase (sGC). Since a diminished activity of vascular sGC has been reported in an animal model of type 2 diabetes, the sGC activity was assayed in vitro in internal mammary artery specimens obtained during bypass surgery from patients with and without type 2 diabetes. The sensitivity of sGC to NO, which is dependent on Fe(2+)-containing heme, was measured in vitro using stimulation with diethylamine NONOate (DEA/NO). In addition, the novel cyclic guanosine monophosphate-elevating compound HMR-1766 was used to test the stimulation of the oxidized heme-Fe(3+)-containing form of sGC. Basal activity of sGC and its sensitivity to stimulation by DEA/NO and HMR-1766 were not different between control and type 2 diabetic patients: maximum stimulation by DEA/NO amounted to 475 +/- 67 and 418 +/- 59 pmol. mg(-1). min(-1) in control and type 2 diabetic patients, respectively. The maximum effects of HMR-1766 were 95 +/- 18 (control subjects) and 83 +/- 11 pmol. mg(-1). min(-1) (type 2 diabetic patients). Hypertension, hyperlipidemia, drug treatment with statins, ACE inhibitors, or nitrates had no effect on sGC activity. In conclusion, the present findings do not support the hypothesis that desensitization of sGC contributes to the pathogenesis of diabetic vascular dysfunction in humans.
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PMID:Nitric oxide-sensitive soluble guanylyl cyclase activity is preserved in internal mammary artery of type 2 diabetic patients. 1544 95

Insulin glargine is a biosynthetic human insulin analog which has been developed by Aventis Pharma (formerly Hoechst Marion Roussel, HMR), for the treatment of types I and II diabetes. In April 1999, HMR filed insulin glargine for approval in both Europe and the US [322507]. In April 2000, the FDA approved insulin glargine (as Lantus) for the treatment of adult patients with type II diabetes mellitus, who require basal insulin for the control of hyperglycemia, and for adult and pediatric patients with type I diabetes mellitus [363836]. Aventis expects to launch this product during 2000 [361988]. In June 2000, the EMEA approved insulin glargine for the treatment of both type I and II diabetes [370984]. In April 1999, the FDA recommended that HMR should initially submit 6-month efficacy and safety data, instead of the usual 12- month data, to hasten the FDA approval procedure. The rest of the phase III data would be added to the filing at a later date [279466]. Insulin glargine is in phase III trials in Japan as a substitute for basal insulin in the treatment of Type I diabetes [216445]. Two formulations of insulin glargine with zinc have also been tested in phase I trials. HOE-71/GT15 and GT80 contain 15 and 80 mu g/ml of zinc. These formulations appear to have longer duration of action with a reduced peak insulin effect [177507]. This insulin analog has a lower receptor binding affinity compared with human insulin, but shows equal potency in vivo [320724]. Insulin glargine was designated as a medium priority project by HMR, which means the project had been set tight deadlines which if not achieved, would have resulted in discontinuation [221118]. In April 2000, Novo Nordisk filed a complaint in Germany against Aventis claiming that the production and sale of insulin glargine infringes two German patents held by Novo Nordisk [364362]. In July 2000, Credit Lyonnais Securities Europe predicted that insulin glargine was likely to enjoy a strong competitive position for several years in Europe and the US, following launch in these territories during 2000, while it was predicted that a registration dossier would be submitted in Japn in 2002. Sales were predicted to reach Euro 600 million by 2005. In April 1999, ABN Amro predicted annual sales of DM 75 million in 2000, rising to DM 200 million in 2002 [328676].
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PMID:Insulin glargine (Aventis Pharma). 1604 68