By Brady Huggett
Amgen Inc. presented interim results from its Phase II trial examining epratuzumab in combination with rituximab to treat relapsed and refractory non-Hodgkin¿s lymphoma, and also reported on a separate Phase II study of another non-Hodgkin¿s lymphoma product, pegfilgrastim, at the 43rd annual meeting of the American Society of Hematology in Orlando, Fla.
The interim data from the Phase II trial suggest epratuzumab may have a beneficial effect when used in combination with rituximab and does not seem to affect rituximab¿s safety profile.
A total of 19 patients ¿ 15 indolent (low-grade) patients and 4 aggressive ¿ received four weekly infusions of epratuzumab followed by rituximab. Fifty-three percent of the indolent population responded as measured by standard criteria ¿ similar to percentages seen in other studies where patients received single-agent rituximab. However, Amgen said seven out of the eight responding indolent patients achieved a complete response.
Amgen is investigating epratuzumab as a single agent in rituximab-refractory patients with indolent non-Hodgkin¿s lymphoma (NHL) and also as a single agent in aggressive NHL. Amgen, of Thousand Oaks, Calif., obtained licensing rights to epratuzumab in North America and Australia from Immunomedics Inc., of Morris Plains, N.J., in December 2000 through a deal valued at up to $308 million. (See BioWorld Today, Dec. 19, 2000.)
The second Phase II study evaluated the efficacy and safety of a single injection of pegfilgrastim (100 mg/kg) compared to a median of 11 daily injections of Neupogen (filgrastim; 5mcg/kg/day) in decreasing the duration of severe neutropenia following cytotoxic chemotherapy in patients with relapsed or refractory NHL or Hodgkin¿s disease. The endpoint was duration of severe neutropenia during cycle 1. In the randomized, open-label study of 60 patients, the duration of severe neutropenia in cycle 1 appeared to be no different for patients in the pegfilgrastim and filgrastim groups ¿ an average of 2.8 days and 2.4 days, respectively.
Amgen submitted a biologics license application with the FDA for pegfilgrastim in March and submitted a marketing authorization application with European regulatory authorities is May. Both applications are under review.
In other news from the American Society of Hematology meeting:
¿ BioTransplant Inc., of Charlestown, Mass., said its researchers established a preclinical model of immune tolerance for cellular transplants using enhanced green fluorescent protein as a model antigenic protein. Enhanced green fluorescent protein is used as a receptor protein in gene transfer protocols because it produces a green color that can be seen in cells.
¿ Celgene Corp., of Warren, N.J., presented data from two Phase I/II trials of Revimid in refractory or relapsed multiple myeloma. Investigators reported that Revimid demonstrated antitumor activity and was generally well tolerated. Revimid has completed the initial phase of a trial in metastatic melanoma and the trial is being expanded by 60 patients. Studies are planned for Revimid in anti-inflammatory diseases, in addition to a recently initiated congestive heart failure trial.
¿ Cell Therapeutics Inc., of Seattle, reported that Trisenox injection can be used to safely treat patients with blood cell cancers such as multiple myeloma, myelodysplastic syndrome and acute promyelocytic leukemia, who have failed to respond to prior treatment. Trisenox is marketed to treat relapsed or refractory acute promyelocytic leukemia. Data were presented on more than 600 patients who were treated with Trisenox. Safety data from the patients showed no deaths due to cardiac arrhythmias, and the side effects associated with chemotherapy rarely occurred.
¿ Corixa Corp., of Seattle, said studies on Bexxar, under review by the FDA, showed it may offer a new treatment option for relapsed or refractory NHL patients and, in particular, for patients whose prognosis is very poor. Bexxar is being studied for the treatment of low-grade or transformed low-grade non-Hodgkin¿s lymphoma and is under review by the FDA. The company said studies show Bexxar provides durable, long-term responses when used either alone or following chemotherapy.
¿ Genta Inc., of Berkeley Heights, N.J., presented preclinical and clinical data supporting the activity of Genasense in chronic lymphocytic leukemia (CLL). Results from a Phase I study using Genasense alone reaffirmed that 3 mg/kg/day was appropriate for extended study of the drug as a single agent. A second presentation showed that Genasense was taken up into CLL cells in culture and induced a higher level of programmed cell death than fludarabine. Genasense is in an ongoing Phase III trial in patients with CLL.
¿ Genzyme Molecular Oncology, of Framingham, Mass., said two oncologists working with Genzyme presented preliminary data showing clinical and immunologic responses from melanoma and breast cancer vaccine trials. In a Phase I/II ex vivo antigen-specific melanoma vaccine trial, preliminary findings showed the approach was well tolerated by the 20 patients, and 14 of them showed immunologic or clinical responses. In the breast cancer vaccine trial, of the nine patients treated, one has shown a complete clinical response as well as an immunologic response to the tumor following vaccination. In those patients where immunologic response data are available, a majority showed a response, the company said.
¿ Large Scale Biology Corp., of Vacaville, Calif., reported news in cancer vaccines, stem cell biology and the development of a new research product for cultivating adult bone marrow cells. It said it has seen excellent safety data from the Phase I trials of its personalized cancer vaccines to treat non-Hodgkin¿s lymphoma. It has been able to manufacture vaccines for nearly 90 percent of patients who qualified for treatment. The company¿s endothelium-derived hematopoietic factor tests showed its ability to enhance hematopoiesis and expand murine antigen-presenting cell progenitors in vivo. A third presentation highlighted the proliferation and engraftment of human bone marrow-derived CD34+ cells in SCID/NOD mice after exposure of these cells to brain-derived microvascular endothelial cells in a co-culture procedure.
¿ Matrix Pharmaceutical Inc., of Fremont, Calif., presented data from a Phase I study of tezacitabine. The trial enrolled 32 patients ¿ 24 with acute myeloid leukemia and eight with acute lymphocytic leukemia. The maximum tolerated dose of 7.5 mg/m2 was determined from the trial. Tezacitabine is a nucleoside analogue that is an inhibitor of ribonucleotide reductase and a DNA chain terminator.
¿ Orphan Medical Inc., of Minneapolis, presented 14 studies incorporating Busulfex (busulfan) Injection. The presentations and abstracts addressed issues including the product¿s use in transplant for multiple myeloma, alternative dosing regimens to allow Busulfex to be used in an outpatient setting and recent advances in nonmyeloablative transplants. Busulfex is a conditioning regimen for bone marrow and stem cell transplants. It was approved by the FDA in February 1999.
¿ SuperGen Inc., of Dublin, Calif., presented data from a Phase II study of rubitecan showing that the oral anticancer drug is active in both chronic myelomonocytic leukemia (CMML) and myelodysplastic syndromes (MDS). Thirty-five evaluable patients who had previously received a minimum of one prior therapy and who were diagnosed with either CMML or MDS were treated. The objective response rate was 28 percent. Hematological improvement was observed in 14 percent, leading to an overall response rate of 42 percent.
¿ ViaCell Inc., of Boston, said its patented cell expansion technology, Selective Amplification, removes mature T lymphocytes from umbilical cord blood stem cell cultures while retaining the population of functional immature T-cell progenitors. Also, studies demonstrated umbilical cord blood stem cell populations expanded and purified by its Selective Amplification technology displayed engraftment ability in the NOD/SCID mouse model, as evidenced by the presence of human DNA in the bone marrow of these animals. Additionally, scientists said the molecule IGFBP-3 results in enhanced quantities of functional stem cell populations when added to cell cultures. ViaCell also highlighted advances in cellular therapy at the meeting.