Pharma NewsBytes: Selected pharma press releases - Dec 1st-17th

LeadDiscovery's intelligence service, DailyUpdates has evolved as a key tool to help all in the drug development sector keep track of breaking journal articles, press releases and pharmaceutical reports. Pharma NewsBytes features selected press releases recently featured on DailyUpdates and offers the reader a leisurely stroll through the past few weeks of activity from within the pharmaceutical industry.

• Progress towards the treatment of Alzheimer's disease [more]
• New approaches to autoimmune diseases and acute and chronic inflammatory disorders [more]
• News from the 26th Annual San Antonio Breast Cancer Symposium[more]
• News listed on DailyUpdates December 17th onwards[more]

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Two press releases stand out in early December in the field of Alzheimer's disease. In the first release, the collaborative approach of MorphoSys and Roche to the development of antibody therapies of Alzheimer's disease is reported to be progressing. According to Datamonitor, successful in vivo results have been achieved using antibodies developed through MorphoSys' human HuCAL antibody technology. This technology is being used to develop antibodies that are highly specific to human amyloid plaques. In an animal study conducted by Roche, systemically administered antibodies showed highly specific binding to amyloid plaques in the brain of transgenic mice that are models for human Alzheimer's disease. Under the terms of the collaboration MorphoSys selected several antibodies from its HuCAL library against the Alzheimer target amyloid beta-peptide (A-beta). After two rounds of optimization the fully human antibodies showed high affinity binding to the target. These antibodies were able to bind specifically to amyloid plaques in human brain sections from Alzheimer patients in vitro. Moreover, the binding of the antibodies dissolved aggregations of A-beta molecules in an in vitro assay. The optimized HuCAL antibodies against A-beta were further tested in an animal model of Alzheimer's disease. After systemic administration the antibodies were shown to cross the blood-brain-barrier and to bind to beta-amyloid plaques within the brain. The selected HuCAL antibodies against A-beta represent unique tools for application in Alzheimer's disease, both diagnostically and therapeutically [more]

A second release (Dec 15) announced the results of a preliminary study of the antibiotic, clioquinol, led by researchers at the University of Melbourne in Australia. Clioquinol appeared to improve cognitive function in patients with Alzheimer's by lowering levels of beta-amyloid "The main importance of studies like this is to attempt to prove the principle that amyloid-lowering agents can stabilize or possibly even reverse cognitive decline in Alzheimer's," said William Thies, vice president of medical and scientific affairs at the Alzheimer's Association. In a pilot trial of 36 patients with moderately severe Alzheimer's disease who received the drug clioquinol, researchers found that beta-amyloid levels declined in the clioquinol group and increased in the placebo group. Patients taking clioquinol also performed better on a test of cognitive ability. The research, which appeared in the December issue of The Archives of Neurology (click here for abstract), suggests that clioquinol works by inhibiting zinc and copper ions from binding to beta-amyloid, helping to dissolve the protein and preventing it from accumulating. "The findings support a proof of concept in humans that a drug targeting metal/beta-amyloid interactions can have a significant effect on beta-amyloid metabolism, and through this, a beneficial modification on the progression of Alzheimer's disease," the researchers said. Still, Thies said that while the trial is promising it is too small to draw definitive conclusions "The sample size is very, very small and the effect is not dramatic." Now the researchers are applying to the U.S. Food and Drug Administration to conduct a bigger trial, of 80 people. But there are substantial safety concerns with clioquinol. The drug, introduced more than 30 years ago as an antibiotic, was withdrawn after several thousand people, mainly Japanese, developed vitamin B deficiencies that in some cases led to blindness. The researchers said they are supplementing their patients with vitamin B and so far have seen no such symptoms. Even so, the company that holds the rights to the drug, Prana Biotechnology Ltd. of Australia, no longer plans to plow money into the drug. It will concentrate on developing derivatives instead.[more].

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SAN DIEGO, Dec. 2 - La Jolla Pharmaceuticals announced the discovery of novel, orally-active small molecules for the treatment of autoimmune diseases and acute and chronic inflammatory disorders. Company scientists have generated highly selective inhibitors of SSAO (semicarbazide-sensitive amine oxidase), an enzyme that has been implicated in inflammatory responses in many tissues and organs. Preclinical studies in animal models of multiple sclerosis, rheumatoid arthritis and acute inflammation have shown that treatment with the company's inhibitors both maintained function and reduced disease activity compared with placebo treatment. "We have discovered several families of potent, orally-active small molecule inhibitors of SSAO that reduce disease in a variety of animal models," said Matthew Linnik, Executive Vice President of Research and Chief Scientific Officer of La Jolla Pharmaceuticals. "The impact of these lead compounds on animal models of multiple sclerosis and rheumatoid arthritis was similar to that of methotrexate, a widely used anti-inflammatory agent. SSAO, also known as vascular adhesion protein-1 or VAP-1, was recently discovered to be a dual-function molecule with enzymatic and adhesion activities and is one molecular target for treatments of rheumatoid arthritis addressed in LeadDiscovery's recent cutting edge pharma report "Rheumatoid arthritis: Emerging drug discovery targets and therapeutic candidates" (click here for access). SSAO contributes to the adhesion of white blood cells to endothelial cells and is greatly amplified in inflamed blood vessels. The enzyme also contributes to the production of molecules that exacerbate inflammation. Increases in the levels of plasma or membrane-associated SSAO have been reported for many inflammation-associated diseases including rheumatoid arthritis, inflammatory bowel disease, diabetes, atherosclerosis, and chronic heart failure. In preclinical studies conducted by company scientists, SSAO inhibitors blocked both the enzymatic and adhesion functions of SSAO and were shown in animal models to be potent inhibitors of disease activity. These results will be presented at the 2nd International Inflammatory & Immune Diseases World Summit on March 8-10, 2004 in Baltimore [more].

On Dec. 3 Advanced Viral Research Corp. announced that its novel immunomodulator AVR118 (formerly known as Product R) has exhibited therapeutic effects in both an animal model of inflammatory arthritis and in a clinical trial of patients with rheumatoid arthritis. In experiments with an animal model of inflammatory arthritis, performed at The Weizmann Institute of Research in Rehovot, Israel, the administration of AVR118 significantly suppressed the development of inflammation in the animals' joints compared to non-treated control animals. The results in the animal model were validated by an open-label clinical trial conducted in Argentina in 27 patients. All patients in the trial had improvement in quality of life including resolution or significant decrease in intensity of pain, the ability to exercise, to perform housework, and to engage in social activities. In addition, all patients showed objective signs of decreased inflammation, and increased mobility, of affected joints. Patients were treated with AVR118 for a period of 90 days and by day 90, all patients had either complete regression or significant decrease of joint swelling. In laboratory experiments ADVR scientists have shown that AVR118 modulates the synthesis of cytokines and chemokines including MCP-1, IL-8, IL-1 beta, and IL-6 [more]

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The 26th Annual San Antonio Breast Cancer Symposium provided the platform for a number of exciting studies. Allos Therapeutics presented positive findings from its Phase 3 clinical trial of the investigational radiation sensitizer RSR13 (efaproxiral). The results demonstrate a significant survival benefit for women with breast cancer and brain metastases who received RSR13 plus whole brain radiation therapy (WBRT) versus WBRT alone. Baldassarre Stea, M.D., Ph.D., Head of the Department of Radiation Oncology at the Arizona Health Sciences Center in Tucson, showed that adding RSR13 to WBRT with supplemental oxygen nearly doubled the median survival rate of patients with breast cancer and brain metastases to 8.67 months versus 4.57 months for patients who received WBRT alone. Patients with breast cancer and brain metastases who were treated with RSR13 plus WBRT also achieved a higher response rate in the brain than the control group (71.7% vs. 49.1%). A statistically significant stable or improvement in quality of life at 3 months was observed in patients receiving RSR13. In general, patients experienced minimal serious adverse events with the most common being hypoxemia, which is dose-dependent and effectively managed with supplemental oxygen. "The presentation of survival and quality of life data at this meeting validates the potential of RSR13 to increase the effectiveness of radiation therapy in breast cancer patients with brain metastases," said Michael E. Hart, President and CEO of Allos Therapeutics. The company is currently submitting a rolling New Drug Application (NDA) for RSR13 as an adjunct to WBRT for the treatment of brain metastases originating from breast cancer to the U.S. Food and Drug Administration (FDA). The FDA granted Fast Track Product designation for RSR13 in November 2000. The company expects to complete its rolling NDA submission this month.[more].

At the same meeting, Merck KGaA announced data from the final analysis of their Theratope® Vaccine Phase III clinical trial in women with metastatic breast cancer. Theratope is an investigational therapeutic cancer vaccine that consists of a synthetic version of the tumour-associated antigen Sialyl Tn (STn) linked to the protein carrier, keyhole limpet hemocyanin (KLH), and is designed to stimulate an immune response to STn. The Phase III trial randomized 1,028 women with metastatic breast cancer. The primary objectives of the trial were to compare time to disease progression and survival in patients receiving Theratope vaccine and those on the KLH control arm of the study. Secondary objectives were to document the product safety profile, to measure anti-STn, anti-OSM, and anti-KLH antibody titres and to evaluate the impact of Theratope vaccine therapy on patients' health-related quality of life. Biomira and its collaborator Merck KGaA announced in June that the Phase III trial of Theratope did not meet the two pre-determined statistical endpoints of time to disease progression and overall survival. However, in one pre-stratified subset of more than 300 women who received hormonal treatment following chemotherapy, those on the Theratope arm appeared to show a favourable trend toward improvement in survival. "We continue exploratory analyses of the Phase III trial data and we are investigating possible theories to explain the findings in this study," said Alex McPherson. "In previous Phase II studies, peak immune responses were seen after 12 weeks, however, time to disease progression for most of the Phase III patients who were not on concurrent hormonal therapy was less than 12 weeks. One possible theory is that when the Phase III patients who were not on hormonal therapy progressed and were taken off Theratope, their immune systems had not had time to obtain a maximum response. This theory suggests that if patients had the opportunity to stay on Theratope longer, as was the case with the patients on concurrent hormonal therapy, this may have allowed their immune systems more time to respond. Based on our assessment of the data to date, we are not planning to seek a registration for this product at this time," said McPherson. "We do, however, believe that there may be scientific rationale from these Phase III data to continue with the development plans for Theratope. Once our strategy has matured, we intend to discuss our plans, which may include a registration trial, with the regulatory authorities."[more].

Coinciding with their much publicized Research Day, GlaxoSmithKline presented data from an early phase, multi-center clinical trial of GW572016. This study showed that GW572016, a reversible inhibitor of two growth factor receptors involved in the proliferation and survival of many solid tumors in a once-daily oral dose, has clinical and biological activity in patients with metastatic breast cancer who have received multiple prior therapies. The presentation came as GlaxoSmithKline announced that GW572016 had received fast-track designation from the U.S. Food and Drug Administration. The FDA granted the designation for treatment of certain patients with refractory advanced or metastatic breast cancer who have failed previous therapies. Howard A. Burris III, M.D., director of drug development at the Sarah Cannon Cancer Center, Nashville, who presented the study results at San Antonio, said that, "although our results must be confirmed by additional clinical trials, they are encouraging. "GW572016 appeared to be active in nearly half the women we evaluated, suggesting that by effectively blocking multiple receptor sites, we eventually may be able to help a larger number of patients with advanced stage breast cancer," Dr. Burris said. "Furthermore, the fact that this therapy can be delivered in a once-daily oral dose brings us closer to an era in which we will be able to manage cancer as a chronic disease." The multi-center study enrolled 67 patients with advanced solid tumors that overexpress the receptor tyrosine kinases, ErbB1 (also termed as EGFR) and/or ErbB2, including 30 women with advanced breast cancer. The principle objectives of the study were to evaluate tolerability and biological effect, and to establish an effective once-daily oral dosing range. The study subjects consist primarily of patients who have received multiple prior therapies and still experienced disease progression. GW572016, which potently inhibits ErbB1 and ErbB2, was tolerated at doses up to 1600 mg per day. Common drug-related adverse events were mild to moderate (Grades 1 and 2) and included diarrhea, rash, nausea and vomiting. Grade 3 adverse events included diarrhea, rash, esophageal reflux and abdominal pain. Among the 30 women with advanced breast cancer, 26 received GW572016 for at least eight weeks. Clinical response was assessed after eight weeks of therapy and every two months thereafter, until disease progression or termination from the study. Dr. Burris reported that within this group, four women experienced a partial response, with treatment duration ranging from 15 to 27-plus weeks. Ten others had disease stabilization (no evidence of tumor growth or new lesions), with treatment duration ranging from 10 to 41-plus weeks. All the patients who had partial responses, and six of the 10 with disease stabilization, were refractory to prior trastuzumab therapy, which targets the ErbB2 pathway. Currently, GW572016 is under investigation in three Phase III studies in advanced/metastatic breast cancer and -- in earlier-phase studies -- a number of other solid tumors [more].

Away from the San Antonio Breast Cancer Symposium, Munich Biotech AG announced positive results from a phase I clinical trial using escalating doses of its taxane based anti-neovascular cytotoxic agent MBT-0206 in patients with metastatic breast cancer showing resistance to anthracycline-containing therapy. MBT-0206 is a paclitaxel based anti-cancer drug designed to destroy tumor blood vessels. It selectively targets and destroys tumor blood vessel endothelial cells that are activated and proliferating, resulting in tumor growth inhibition or regression. This is achieved by a combination of two active ingredients, EndoTAG (TM) and Paclitaxel both acting synergistically. EndoTAG (TM) is a proprietary lipid-based complex that is proven to function by selectively targeting angiogenic endothelial cells. Preliminary data of the study, which was conducted at 6 European centers, showed that the disease control rate was 44 %. In an amendment of this study a number of patients that showed at least disease stabilization after 4 months were treated another 3 to 4 months. There was no sign of resistance as disease did not progress in either of these patients. One patient that had a stable disease after 4 months showed partial response (tumor shrinkage) after 7 months. These data follow the previously reported single-agent anti-tumor activity of MBT-0206 in a phase I study in patients with metastatic or advanced, unresectable colorectal cancer. The open label multi-center phase I study was conducted to evaluate safety and efficacy of the drug. All of the 32 evaluable patients (median age 53 years), received low doses of MBT-0206 monotherapy with initially 3 cycles over 3 months. MBT-0206 has been well-tolerated in this patient population. "We are very encouraged by these results indicating that MBT-0206 appears safe even after 8 months and exhibits clinical benefit as low-dose monotherapy in advanced solid tumors" commented Kurt Naujoks, PhD, President and CEO of Munich Biotech. "Especially the fact that resistance was not observed over 8 months treatment in the amended part of the study is quite remarkable, as resistance is one of the biggest unsolved problems of conventional taxane chemotherapy. With our innovative treatment that attacks tumor blood vessels we may help to overcome this in the future. We are committed to move MBT-0206 into clinical phase II as single agent and in combination therapy. Its good tolerability may allow us to perform these studies not only in clinics but also in outpatient settings. Its full potential may be exploited in combination with complimentary acting conventional chemotherapy that targets tumor cells directly." [more].

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Press releases featured on DailyUpdates 17th December onwards:

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• New Drug XOPENEX Effective in Treating Asthma Patients - Study Shows Dramatic Decline In Need for Hospitalizations In Children With Acute Asthma Attacks
• Amylin says FDA seeking more data on diabetes drug
• NPS Pharmaceuticals (NPSP) Begins Clinical Trial In Migraine, Appoints Chief Medical Officer
• Positive results confirmed in final report for Active Biotech's TTS cancer product
• deCODE and Roche Announce Milestones in the Pharmacogenomics of Asthma and Hypertension