ISSN:1174-5886    

出版商:ADIS    

年代:2004

数据来源: ADIS

摘要:

ObjectiveTo evaluate the response rates, survival and toxicity of treatment with antineoplaston A10 and AS2-1 (ANP) in the first 12 children enrolled in our studies diagnosed with incurable recurrent and progressive multicentric glioma.Patients and methodsThe patients’ median age was 9 years. Six patients were diagnosed with pilocytic astrocytoma, four with low-grade astrocytoma and one with astrocytoma grade 2. In one case of visual pathway glioma, a biopsy was not performed due to a dangerous location. Patients received ANP intravenously initially and subsequently orally. The average duration of intravenous ANP therapy was 16 months and the average dosage of A10 was 7.95 g/kg/day and of AS2-1 was 0.33 g/kg/day. The average duration of oral ANP was 19 months and the average dosage of A10 and AS2-1 was 0.28 g/kg/day. Responses were assessed by MRI according to the National Cancer Institute’s criteria and confirmed by PET scans in some cases.ResultsComplete response was accomplished in 33%, partial response in 25%, and stable disease in 33% of patients, and there was no progressive disease. One patient was non-evaluable due to only 4 weeks of ANP and lack of follow-up scans. One patient who had stable disease discontinued ANP against medical advice and died 4.5 years later. Ten patients are alive and well from 2 to >14 years post-diagnosis. Only one case of serious toxicity of reversible tinnitus, of one day’s duration, was described. The study continues with accrual of additional patients.ConclusionThe results of the present study are favourable in comparison with radiation therapy and chemotherapy. We believe that confirmation of these results through further studies may introduce a new promising treatment for incurable paediatric brain tumours.

ISSN:1174-5886    

出版商:ADIS    

年代:2004

数据来源: ADIS

ISSN:1174-5886    

出版商:ADIS    

年代:2004

数据来源: ADIS

ISSN:1174-5886    

出版商:ADIS    

年代:2004

数据来源: ADIS

摘要:

Gadofosveset [MS 325, MS 32520, Vasovist, ZK 236018], a gadolinium-based chelate, is an injectable angiography imaging agent for use in magnetic resonance imaging (MRI) scans. The agent is being developed by EPIX Medical (formerly Metasyn) for diagnostic imaging of blood vessels of the cardiovascular system.Gadofosveset has potential as an alternative to the range of x-ray, invasive, catheter-based angiograms and thallium stress tests currently used in the diagnosis of coronary artery disease. The agent may also have applications in the diagnosis of peripheral vascular disease, thrombosis and breast cancer. Unlike conventional MRI contrast agents, gadofosveset binds to serum albumin in the blood and moves with the blood through the arteries and veins for an extended period of time before being excreted by the kidneys. The MRI with gadofosveset allows 3D images of the whole body to be accessed in one imaging session. Moreover, it makes it possible to view vessel structures.EPIX Medical has acquired an exclusive licence from the Massachusetts General Hospital to a certain technology, including patents and patent applications, that relates to the company's product candidates such as gadofosveset.EPIX Medical, Mallinckrodt (Tyco International) and Schering AG signed several agreements to develop, manufacture and market gadofosveset (formerly known as Mallinckrodt's AngioMARK®). Initially, in June 2000 Schering AG acquired worldwide exclusive rights (except for Japan) from EPIX Medical to develop and market gadofosveset. Under the terms of the agreement, EPIX Medical is responsible for the completion of clinical trials and filing for approval in the US, while Schering AG undertakes responsibility for clinical investigation of gadofosveset outside the US. Mallinckrodt is responsible and will undertake a long-term supply contract for gadofosveset for clinical development and sales. Schering's subsidiary Berlex will market the product in the US after the approval via its 100 sales representatives.In January 2001, EPIX Medical reacquired the Japanese rights for gadofosveset from Daiichi Radioisotope Laboratories and exclusively licensed them to Schering AG. With this agreement, Schering AG has worldwide rights for gadofosveset. The financial terms of the Japanese rights agreement included a US$3 million upfront fee, and additional milestone payments from Schering AG to EPIX Medical.On 16 December 2003, EPIX announced that it submitted an NDA to the US FDA for gadofosveset for vascular imaging using magnetic resonance angio-graphy (MRA). This is the first NDA filed for approval with the FDA for a MR contrast agent for the primary indication of MRA. The NDA is based on the results of 18 clinical trials in 1438 patients who received gadofosveset.[1]In February 2004, EPIX Medical announced that the NDA for gadofosveset was accepted for filing by the FDA and would proceed through a standard review cycle.[2]The approval for gadofosveset is expected at the end of 2004. In January 2004, Schering reported at the JP Morgan Healthcare Conference that it plans a product launch in the US sometime in 2005.EPIX and Schering have completed four phase III studies in patients with suspected atherosclerotic disease in the aortoilliac, pedal and renal arteries for inclusion in the NDA submission. These trials were conducted at 86 clinical sites and involved 782 patients. The blinded reading of almost 4000 vessels showed that gadofosveset improved diagnostic accuracy of MRA compared with non-contrast MRA. The diagnostic efficacy of gadofosveset-enhanced MRA was comparable to that of x-ray angiography.[3]These trials were initiated in accordance with the recommendations of the FDA to expand gadofosveset's target indication of aortoiliac occlusive disease to a broader peripheral vascular disease indication.[4]In July 2004, EPIX Medical initiated a multicentre, post-NDA trial with gadofosveset for use in high-resolution vessel imaging for the characterisation of vascular wall structures and vulnerable plaque. The trial will investigate whether gadofosveset has an extended imaging window above and beyond that which was demonstrated in phase III studies.[5]In June 2004, Schering submitted gadofosveset for approval in Europe for use as a conrast agent for MRA.[6]The launch in Europe is projected for 2006 (Schering, Annual Report 2003).Schering has initiated its first feasibility, multicentre (Europe, US), phase III clinical trial with gadofosveset for the imaging of coronary artery disease in approximately 50 patients. This trial follows a successful completion of phase II feasibility studies with gadofosveset in the imaging of coronary artery disease and breast tumour imaging.In July 2004, EPIX announced that it initiated a multicentre phase IIa feasibility clinical trial with gadofosveset in the imaging of both the coronary arteries and myocardial perfusion.[7]EPIX Medical is conducting preclinical investigation with gadofosveset for myocardial perfusion and rheumatoid arthritis.EPIX Medical, Mallinckrodt and Pfizer have announced a collaboration to investigate MRI imaging with gadofosveset in the diagnosis and monitoring of female sexual arousal dysfunction (FSAG). EPIX Medical completed enrolment in a phase II clinical feasibility trial using gadofosveset for this indication. It is estimated that more than 10 million women in the US suffer from FSAD.EPIX Medical was granted a US patent No. 6,676,929 covering composition-of-matter claims for the chemical structure of gadofosveset. The patent is entitled "Diagnostic Imaging Contrast Agents With Extended Blood Retention". Its expiry date is August 2015. However, under provision of the Hatch-Waxman Act, the terms of the patent may be extended following FDA approval.[8]In its 2002 Annual Report, Schering predicted that gadofosveset has the potential to reach peak sales of EUR100 million, 3 years after launch – at the time, launch in the US was anticipated in 2005.Earlier, at an analyst presentation in Berlin in March 2002, the company stated that launch in the US was planned for 2004.

ISSN:1174-5886    

出版商:ADIS    

年代:2004

数据来源: ADIS

摘要:

Icatibant [HOE 140, JE 049] is a potent, specific and selective peptidomimetic bradykinin β2-receptor antagonist. It has a modified peptide structure, and is the first bradykinin receptor antagonist to act on the guinea-pig trachea without demonstrating agonist effects. Icatibant was originated by Hoechst Marion Roussel (now Sanofi-Aventis).Jerini is seeking a partner for development and marketing of icatibant for the treatment of refractory ascites in liver cirrhosis, angioedema and burns.In August 2004, Aventis merged with Sanofi-Synthelabo to form Sanofi-Aventis.Icatibant has shown an excellent safety profile in phase I studies. In December 2003, Jerini demonstrated positive results in the phase IIa study. Results obtained were statistically significant and clinically relevant. At the BIO 2004 International Annual Convention (BIO-2004) [San Francisco, CA, USA; 6-9 June 2004], Jerini reported plans to initiate phase IIb trials in this indication in the second half of 2004.[1]Positive results from an icatibant formulation comparative study, in patients with acute attacks of hereditary angioedema, were announced in August 2004; IV and SC formulations showed no difference in efficacy and safety.[2]It was announced in September 2004 by Jerini that a pivotal study, known as For Angioedema Subcutaneous Treatment (FAST) 1, had been initiated in the US and Canada. The protocol of a European study, to be known as FAST 2, is to be submitted to the authorities in September 2004.[3]Jerini expects to launch the product in 2006.The US FDA granted icatibant, for the treatment of hereditary angioedema, fast-track designation in July 2004.[4]In January 2003, the European Agency for the Evaluation of Medicinal Products granted icatibant orphan drug status in Europe for the treatment of angioedema. In November 2003, Jerini announced that effective December 2003, icatibant had orphan drug status in the US for the same indication.[5]

ISSN:1174-5886    

出版商:ADIS    

年代:2004

数据来源: ADIS

摘要:

Santarus Inc. is developing an immediate-release formulation of omeprazole in combination with an antacid (sodium bicarbonate) as a powder for suspension, known as Acitrel™ [SAN 05] and also as Rapinex®powder for oral suspension. This omeprazole powder suspension will be used to treat gastrointestinal haemorrhage, gastro-oesophageal reflux disease, heartburn and peptic ulcers.Acitrel™ is based on technology licensed from the University of Missouri. Santarus have also licensed technology from Tulane and North Carolina Universities relating to potential treatments for gastrointestinal (GI) diseases.Santarus has licensed exclusive, worldwide rights to patent applications covering specific combination formulations of proton pump inhibitors (PPIs) and antacids for treating various upper GI diseases and disorders.Santarus plans to license the development, distribution and marketing rights of omeprazole powder for oral suspension 20mg outside the US, to one or more well established pharmaceutical companies.The US FDA has requested that Santarus pursue a name other than Rapinex®for the product. Santarus is currently discussing potential alternative names for the product with the FDA.Santarus announced positive results in August 2003 from a phase III trial comparing oral Acitrel™ (Rapinex®40mg) with intravenous cimetidine in preventing upper GI bleeding in 359 critically ill adult patients. Santarus has also completed an open-label clinical trial in 243 patients, including 97 patients with gastric ulcers, evaluating the safety of this omeprazole 40mg powder suspension for an 8-week period.In connection with the NDA for omeprazole powder suspension 40mg, Santarus provided notice to the NDA holder for Prilosec®delayed-release capsules and related patent owners that omeprazole powder suspension 40mg does not infringe currently listed patents for Prilosec®or that those patents are invalid.[1]

ISSN:1174-5886    

出版商:ADIS    

年代:2004

数据来源: ADIS

摘要:

Amgen is developing a recombinant human form of keratinocyte growth factor (rHu-KGF) called palifermin [AMJ 9701]. Keratinocyte growth factor (KGF, fibroblast growth factor 7, FGF-7) is a form of an endogenous epithelial tissue growth factor that stimulates the growth of cells on the surface of the gastrointestinal tract. Palifermin is being developed for oral mucositis (stomatitis), for which it is undergoing review by the US FDA.At BioSquare-2004, Biovitrum stated that it has entered into an agreement with Amgen, under which Biovitrium has co-promotion rights to palifermin in Nordic countries, including Scandinavia and Iceland.Amgen also plans to investigate the efficacy and safety of palifermin in patients with oral mucositis associated with other forms of chemotherapy. Amgen has stated that palifermin is also undergoing phase II trials in patients with solid tumours.

ISSN:1174-5886    

出版商:ADIS    

年代:2004

数据来源: ADIS

摘要:

Safinamide [NW 1015, PNU 151774E; FCE 26743] is a potent anticonvulsant and antiparkinsonian compound that is being developed by Newron Pharmaceuticals in Europe. It has been shown to antagonise the calcium and sodium channels, as well as inhibit monoamine oxidase type-B (MAO-B). Phase III trials for the treatment of Parkinson's disease are underway in Germany and Europe, while phase II trials in patients with epilepsy are ongoing in Italy.Newron Pharmaceuticals was founded at the end of 1998 after Pharmacia & Upjohn announced its worldwide restructuring programme.Newron obtained the rights to safinamide, which Pharmacia Corporation (now Pfizer) had been developing as PNU 151774E. Safinamide was originated by Farmitalia-CarloErba in Italy. Newron now owns all intellectual property associated with the drug.A multinational phase II trial for Parkinson's disease in Europe has shown positive results in slowing the progression of the disease; however, due to the placebo-effect seen in this study, a longer (6-month) phase IIb study is planned for the second quarter of 2003.In July 2003, Newron received an IND from the US FDA authorising a phase I trial to confirm that no dietary restrictions are needed in patients while being treated with safinamide. This study is be conducted in 12 healthy volunteers at the University of Vienna, Austria, and will be followed by efficacy studies in Parkinson's disease in the US.[1]Five phase I trials were completed in April 2001 in Switzerland. Safinamide combines sodium and calcium channel modulatory activity with monoamine oxidase B inhibition.

ISSN:1174-5886    

出版商:ADIS    

年代:2004

数据来源: ADIS

摘要:

Tamibarotene [AM 80, retinobenzoic acid, Amnoid™, Tamibaro] is a novel synthetic retinoid that is in development with Nippon Shinyaku as a potential treatment for acute promyelocytic leukaemia (APL) and is pending approval in Japan. Tamibarotene was being developed by Shionogi in Japan but the company subsequently discontinued its involvement. Various nonindustrial sources, such as the University of Tokyo, Japan, have also played a role in the development of tamibarotene.Nippon Shinyaku has licensed the rights to tamibarotene from Toko Pharmaceutical Industries for the treatment of acute promyelocytic leukaemia, according to Nippon Shinyaku's June 2004 pipeline update. However it is unclear when Toko Pharmaceutical Industries acquired rights to the compound.

ISSN:1174-5886    

出版商:ADIS    

年代:2004

数据来源: ADIS