Amgen Inc. reported additional Phase III data at the 45th annual meeting of the American Society of Hematology demonstrating that treatment with its investigational palifermin product aided patients with mouth and throat soreness as a result of hematological malignancies that stem from oral mucositis.

Palifermin (recombinant human keratinocyte growth factor, or rHuKGF) was associated with a statistically significant and clinically meaningful improvement in mouth and throat soreness as a result of high-dose chemotherapy and radiotherapy with peripheral blood progenitor cell transplants.

The study's 212 patients reported daily on their mouth and throat soreness, as well as their limitation in carrying out daily activities. On average, patients receiving palifermin reported a reduction in soreness of 54 percent compared to the placebo arm (p=0.0001). The reduction in soreness translated into, on average, a 40 percent improvement in palifermin-treated patients' ability to eat, drink, swallow, sleep and talk (p<0.001).

Half the patients received palifermin, said Thousand Oaks, Calif.-based Amgen.

In other news from the conference:

• Antigenics Inc., of New York, said findings from a Phase II study of Oncophage vaccination showed indications of clinical activity in eight out of 14 evaluable patients with newly diagnosed or relapsed low-grade, indolent non-Hodgkin's lymphoma (NHL). The open-label, single-arm study uncovered one partial response, two minor responses and five disease stabilizations, and all eight patients were either previously untreated or had received only one prior treatment regimen. In an interview with Reuters, the company's CEO said he expects to close an Oncophage partnership deal by the end of the year that could be worth between $1 billion and $2 billion. Antigenics also reported updated results from an ongoing Phase I study of HSPPC-70 in combination with Gleevec (imatinib mesylate, Novartis AG) for treatment of chronic myelogenous leukemia. Investigators reported that of the 17 evaluable patients, 11 experienced a reduction in levels of cytogenetic or molecular disease burden; immunological response to vaccination has been measured in 11 of the 17; and nine demonstrated an increased level of interferon gamma-producing T cells.

• Celgene Corp., of Warren, N.J., said clinical data suggest that Revimid (CC-5013) has potential as an approach to therapy for transfusion-dependent patients with myelodysplastic syndrome. Findings also showed that the drug might target MDS through multiple mechanisms of action including inhibiting growth factors and inflammatory proteins, re-establishing normal cell life cycles, inducing death or cell-cycle arrest of the abnormal MDS clones, and suppressing the growth of new blood vessels that feed malignant cells. Findings from a separate Phase II study pointed to the drug's use as a therapeutic approach for patients with refractory or relapsed multiple myeloma. Investigators reported that 73 of 91 evaluable patients with progressive disease showed a reduction or stabilization in their paraprotein levels, a measure of tumor burden. Phase II data on another Celgene product, Actimid (CC-4047), showed its ability in treating refractory or relapsed multiple myeloma. Investigators reported that 23 of 24 patients treated with daily dosing achieved stabilization of disease or better, as did 18 of 20 patients treated with alternate-day dosing.

• Cell Therapeutics Inc., of Seattle, said the combination of its marketed product Trisenox (arsenic trioxide) with an analogue of vitamin A, all-trans retinoic acid, resulted in complete response rates in excess of 90 percent with newly diagnosed or previously untreated acute promyelocytic leukemia. Other data showed that an investigational combination of Trisenox with low-dose chemotherapy (melphalan) and vitamin C produced a high rate of long-lasting responses in 10 heavily pretreated patients with relapsed or refractory multiple myeloma. The regimen improved kidney function in patients with severe myeloma kidney damage, preventing the need for those with kidney dysfunction to go on dialysis. Separately, Novuspharma SpA said Phase I results showed a major objective response rate of 77 percent when Pixantrone was administered instead of doxorubicin as part of the CHOP regimen in patients with relapsed aggressive NHL. Among 22 evaluable patients, 13 had a complete response, with four experiencing a 50 percent or greater shrinkage in their tumor. The companies announced their merger this summer. (See BioWorld Today, June 18, 2003.)

• Genta Inc., of Berkeley Heights, N.J., said results from two studies suggest that its lead cancer compound, Genasense (oblimersen sodium), enhances the activity of many types of chemotherapy in multiple myeloma patients. One trial showed a major clinical response among 12 of 20 evaluable advanced myeloma patients who received escalating doses of Genasense and Thalomid (thalidomide, Celgene Corp.), plus high-dose dexamethasone. Separately, of nine evaluable refractory myeloma patients with Genasense plus VAD (a standard drug combination including vincristine, doxorubicin and dexamethasone), four have achieved a partial response and three have achieved a minor response.

• Geron Corp., of Menlo Park, Calif., said preclinical data showed that systemic administration of GRN163 resulted in decreased tumor burden and increased survival, compared to a saline control and the maximum tolerated dose of doxorubicin, in mice bearing disseminated human myeloma that invades the bone marrow. In a separate series of in vitro and in vivo studies using the same human myeloma tumor cells, GRN163L (formerly called GRN719) showed greater effects on telomerase activity, telomere length, cancer cell proliferation and apoptosis than GRN163.

• Human Genome Sciences Inc., of Rockville, Md., reported interim Phase I results showing LymphoRad (131) to be well tolerated and biologically active in NHL patients. Nuclear imaging following the therapeutic doses confirmed that the drug targeted tumor cells in all six patients. Another ongoing study is evaluating LymphoRad in patients with relapsed, refractory multiple myeloma. Also, the drug's administered radioactivity has a terminal half-life of about 18 to 23 hours. Separate preclinical results on two other investigational products, HGS-ETR1 and HGS-ETR2, show that both are capable of inducing dose-dependent cell death across all malignancies tested, but with some variability among the cell lines.

• ILEX Oncology Inc., of San Antonio, said interim Phase II results revealed a 34 percent overall response rate in 29 children with acute myelogenous leukemia treated with clofarabine, with one complete marrow remission in the absence of platelet recovery and nine partial remissions. Of those responders, seven had a reduction in their leukemic cell count that was sufficient to allow them to go on to receive bone marrow transplants. Among 36 pediatric acute lymphoblastic leukemia patients, there was a 25 percent overall response rate, including three complete remissions, three complete marrow remissions in the absence of platelet recovery and three partial remissions. ILEX is the North American co-development partner of Bioenvision Inc., of New York, which holds the compound's rights outside the U.S.

• Ligand Pharmaceuticals Inc., of San Diego, said Ontak (denileukin diftitox) might benefit patients with chronic lymphocytic leukemia, B- and T-cell NHL, and graft-vs.-host disease that is steroid resistant or refractory after allogeneic hematopoietic stem cell transplantation. Among 39 evaluable patients with B- and T-cell NHL, data indicated that Ontak benefited 54 percent, with four achieving a complete response, seven with a partial response and 10 with stable disease. Among five evaluable chronic lymphocytic leukemia patients, two had a partial response, two had minor response, and one patient had an overall response that included a more than 30 percent reduction in nodal size.

• Medarex Inc., of Princeton, N.J., said its fully human antibody, MDX-060, demonstrated clinical activity, including one complete response and two partial responses, in a Phase I/II study in patients with Hodgkin's disease and anaplastic large-cell lymphoma. In addition, stable disease was observed in nine of 29 evaluable patients. Of the nine, seven were in the highest-dose cohort.

• Millennium Pharmaceuticals Inc., of Cambridge, Mass., said results from two Phase II trials of Velcade (bortezomib) have shown early signs of antitumor activity in NHL patients. A 40-patient study resulted in a 50 percent overall response for 20 of 22 evaluable patients in the mantle-cell lymphoma group, including four complete responses, six partial responses and two patients with stable disease. The other trial showed that six of eight evaluable follicular lymphoma patients had major responses, while among evaluable mantle-cell lymphoma patients, five achieved partial responses and three experienced stable disease.

• NeoRx Corp., of Seattle, said long-term follow-up data from its Phase I/II trial of STR (skeletal-targeted radiotherapy) resulted in a 90 percent three-year survival rate for multiple myeloma patients treated with the dose planned for NeoRx's Phase III trial of the product, in combination with high-dose melphalan chemotherapy and autologous stem cell transplantation. The company compared its findings to three-year survival data from the International Bone Marrow Transplant Registry, which reports a 48 percent to 59 percent range for myeloma patients following high-dose chemotherapy and autologous transplantation.

• Trigen Ltd., of London, said preclinical studies with a neutralizing agent labeled TGN 212 showed a specific, rapid and complete reversal of the anticoagulant properties of its direct thrombin inhibitors, oral TGN 167 and intravenous TGN 255, which are both in clinical development. The company said it plans to develop TGN 212 in parallel with TGN 167 and TGN 255 to provide physicians with anticoagulants whose effect can be neutralized in both emergency out-patient and operative situations.

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