Pfizer development phase

Sildenafil citrate originally entered development as a candidate for the treatment of angina, but the early clinical results were disappointing. In 1994 Pfizer ran a small phase Ila trial with 12 patients suffering from male erectile dysfunction. Ten of those patients showed major improvements in their erections. Suddenly the project changed overnight. Sildenafil citrate had been the lowest-priority project in the Pfizer development portfolio, and now it became one of the highest. The medicinal... 

Apart from these two Vertex compounds, only one other caspase inhibitor, BDN-6556, has been used in clinical trials. This compound belongs to the class of oxamyl dipeptides and was originally developed by Idun Pharmaceuticals (taken over by Pfizer). It is the only pan-caspase inhibitor that has been evaluated in humans. BDN-6556 displays inhibitory activity against all tested human caspases. It is also an irreversible, caspase-specific inhibitor that does not inhibit other major classes of proteases, or other enzymes or receptors. The therapeutic potential of BDN-6556 was first evaluated in several animal models of liver disease because numerous publications suggested that apoptosis contributes substantially to the development of some hepatic diseases, such as alcoholic hepatitis, hepatitis B and C (HBV, HCV), non-alcoholic steato-hepatitis (NASH), and ischemia/reperfusion injury associated with liver transplant. Accordingly, BDN-6556 was tested in a phase I study. The drug was safe and... 

On 2nd December 2006, Pfizer, whose CETP inhibitor torcetrapib (CP-529414) was the first compound aimed at this target, announced that its development had to be stopped in phase III. Of 7500 patients who were given a combination of torcetrapib and atorvastatin, 82 had died, while in the other arm of the study, where patients were given atorvastatin alone, only 51 of 7500 patients had died. There was also a significant rise in blood pressure observed in the group that received torcetrapib. 

Although no biopharmaceutical product delivered to the bloodstream via the pulmonary route has been approved to date, several companies continue to pursue active research and development programmes in the area. Amongst the leading product candidates is Exubera , an inhalable dry powder insulin formulation currently being evaluated by Pfizer and Aventis Pharma in Phase III clinical studies. The inhaled insulin is actually more rapidly absorbed than if administered subcutaneously and appears to achieve equivalent glycaemic control. While promising, final approval or otherwise of this product also depends upon additional safety studies which are currently under way. 

There are several new factor Xa inhibitors currently under development. One is apixaban 40 (BMS-562247), which is in Phase III clinical trials and, if approved, will be marketed by joint venture of Bristol-Myers Squibb and Pfizer for prevention of venous thromboembolism. The other factor Xa inhibitor being developed is otamixaban 41, which is being investigated by Sanofi-Aventis in Phase II clinical trials (at the time of writing) as a treatment for acute coronary syndrome. 

A third area to consider is the generation of an enhanced product that adds value to the original finished dosage form. Product enhancements include, for example, other forms of dehvery (e.g., transder-mal, nasal, inhalable, etc.) or new formulations. Examples among the biopharmaceuticals are the development of inhaled insulins, e.g., Exubera currently in phase III clinical trials developed by Nektar Therapeutics, Pfizer, and Aventis (admittedly, this work is not driven by a potential generic threat, but primarily by the enormous market potential of an insuhn that does not have to be injected) (see also Part VI, Chapter 2). 

Little information is in the public domain regarding a second Rigel Syk inhibitor R343, believed to be structure (7.10).37 Pfizer licensed the compound from Rigel at the preclinical stage for development as an inhaled drug for the treatment of allergic disorders. To date the compound has completed Phase I... 

Pfizer had been cooperating with the Bureau of Mines on the process since its scale-up to the Arizona pilot plant. The company decided to take a more active role in the investigation and development of the process when the copper smelter demonstration was completed in 1971. Working closely with the Bureau of Mines, Pfizer constructed a laboratory pilot unit in which the viability of the process was confirmed. This was followed by a two-phase laboratory program consisting of an exhaustive study of potentially competitive absorption systems and elucidation of the process chemistry. 

Among several new SERMs in clinical evaluations are the two 2-phenylindole analogs, bazedoxifene [13] and pipendoxifene [14]. The only structural difference between these two indole molecules is the side chain amine moiety pipendixifene bears piperidine while bazedoxifene contains azepane. Bazedoxifene is being developed for the prevention and treatment of postmenopausal osteoporosis. It is approved in the European Union, and is currently in the late phases of review by the US Food and Drug Administration. When approved, bazedoxifene will be marketed by Pfizer under the tradename Viviant in the US and Conbriza in the EU. Pipendoxifene was used in phase 11 studies as a treatment for metastatic breast cancer. However, pipendoxifene was classified as the backup to bazedoxifene. Presumably, it would not be developed further unless bazedoxifene failed. 

PDGF receptor p (PDGFRB), and c-kit, a cytokine receptor expressed on the surface of hematopoietic stem cells as well as other cell types. As compared with the two drugs on the market, sorafenib (Nexavar) by Bayer Pharmaceuticals Corp. and Onyx Pharmaceuticals, Inc. and sunitinib (Sutent) by Pfizer, Inc., cediranib inhibits VEGFR targets with improved potency. It is currently in Phase II/III development for advanced non-small cell lung cancer and advanced colorectal cancer. 

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