Protein Design Labs Inc. reported disappointing results of a Phase II study at the 43rd annual Meeting of the American Society of Hematology (ASH) in Orlando, Fla., but the company is planning a new course of action.
The partial, preliminary data from its Phase II trial of Remitogen (SMART 1D10), a humanized antibody being evaluated in patients with relapsed or refractory low-grade or follicular non-Hodgkin¿s lymphoma, were presented by investigator Brian Link. The multicenter, open-label, two-arm, randomized study in 60 patients began in February and is evaluating the safety, overall response rate and response duration of two different dosing regimens of Remitogen. The primary efficacy endpoint is the percentage of patients who achieve complete and/or partial tumor regression at any point during the study.
¿We have evaluated 25 patients and thus far have seen one partial response and no complete responses,¿ Link said in a statement. ¿In addition to the partial response, 10 patients now have stable disease and 14 patients have experienced disease progression. A number of patients have been noted to progress early, suggesting a selection bias toward those with aggressive disease.¿
The Fremont, Calif., company is therefore taking a different course of action.
¿In the Phase I study of Remitogen in non-Hodgkin¿s lymphoma, most responses were seen after study day 120,¿ Daniel Levitt, the company¿s president of R&D, said in a statement. ¿Partial data from this Phase II study show disease progression occurring in 12 of 14 patients earlier than study day 120, indicating a patient group whose disease is more difficult to control than in the Phase I study. Because of this early progression, we plan to amend the study protocol to include three-times weekly dosing for four weeks to deliver more drug early in the course of treatment, and will treat 20 patients with the new dosing regimen.¿
PDL¿s stock (NASDAQ:PDLI) fell $7.21 Monday, or 19 percent, to close at $30.74.
In other news from the American Society of Hematology meeting:
¿ Ariad Pharmaceuticals Inc., of Cambridge, Mass., said for the first time that an Ariad small-molecule drug robustly activates and precisely controls naturally occurring, endogenous genes that stimulate growth of new blood vessels. This drug controls a gene-specific regulatory protein introduced into target cells. Vascular endothelial growth factor, the angiogenic gene activated in this study, has been shown to restore blood flow and is being studied as a potential new treatment for coronary artery and peripheral vascular diseases.
¿ BioTransplant Inc., of Charlestown, Mass., reported that a mild course of chemotherapy, including in some cases MEDI-507 ¿ the company¿s T-cell depleting monoclonal antibody ¿ followed by bone marrow transplantation, was found to positively affect the treatment of large B-cell lymphoma (L-BCL) in patients. Eight of 19 evaluable patients achieved a response (five complete, three partial) including three of 10 HLA matched patients and five of 10 HLA mismatched patients. Of these 20, five patients are alive and progression-free 13 to 52 months after transplant.
¿ Cell Genesys Inc., of Foster City, Calif., reported that a Phase I trial of GVAX cancer vaccine in patients with refractory or relapsed acute myelogenous leukemia (AML) and pre-leukemia demonstrated clinical safety and the induction of antitumor immunity following GVAX vaccination. The interim data include results on five patients with AML or pre-leukemia. All five demonstrated a biopsy-proven immune response at the vaccine site following treatment with GVAX. Additionally, a patient whose disease had relapsed then developed a strong immune response and has ongoing stable disease at 22 months following treatment. Cell Genesys recently initiated a multicenter Phase II trial of GVAX in up to 50 patients with AML.
¿ Cell Pathways Inc., of Horsham, Pa., said CP461 selectively triggered programmed cell death, or apoptosis, in primary leukemic cell samples from patients with chronic lymphocytic leukemia (CLL). At the same time, the drug had a marginal pro-apoptotic effect on normal peripheral blood white cells. These data support the potential of the company¿s second-generation selective apoptotic antineoplastic drug (SAAND) as a treatment for CLL. In work done in other cell systems, CP461 and other SAAND compounds have been shown to selectively trigger cell death by apoptosis in abnormally growing cancerous and precancerous cells but not in normal cells by inhibiting certain cyclic GMP phosphodiesterase enzymes.
¿ Cell Therapeutics Inc., of Seattle, reported that Trisenox (arsenic trioxide) injection can be used to safely treat patients with blood cell cancers such as multiple myeloma, myelodysplastic syndrome (MDS), and acute promyelocytic leukemia (APL) who have failed to respond to prior treatment regimens. Cell Therapeutics markets Trisenox to treat relapsed or refractory APL, a life-threatening blood cancer. Data from more than 600 patients showed no deaths due to cardiac arrhythmias, and that the side effects prevalent with standard chemotherapy, including hair loss and mucositis (mouth sores and ulcers), rarely occurred in patients treated with Trisenox.
¿ Coley Pharmaceutical Group, of Wellesley, Mass., reported Phase I results of its lead product to treat cancer, CpG 7909, an immunostimulatory oligonucleotide tested in patients with relapsed or refractory non-Hodgkin¿s lymphoma. The results show that CpG 7909 infusions were well tolerated and produced positive stimulation of the immunological responses measured in the study. The study measured CpG 7909 at escalating doses as a stand-alone treatment in 16 patients to determine the maximum tolerated dose that could be safely administered. Patients were assigned to one of six groups and received three weekly, two-hour infusions of CpG 7909 at doses ranging from 0.01 to 0.64 mg/kg.
¿ GenStar Therapeutics Corp., of San Diego, released preclinical and clinical data from its ongoing gene therapy studies to treat hemophilia A, in which a defect in the Factor VIII gene decreases the production of the Factor VIII protein essential for blood clotting. In both a preclinical and clinical setting, researchers administered the company¿s Max-Ad Factor VIII gene therapy product, a gene delivery system derived from a common cold virus. One patient demonstrated expression of Factor VIII (approximately 1 percent) that was sustained for four months. In animal models, Max-Ad Factor VIII treatment for hemophilia A led to increased and sustained therapeutic levels of Factor VIII protein despite the presence of neutralizing anti-adenoviral antibodies.
¿ Genta Inc., of Berkeley Heights, N.J., reported new clinical and preclinical data supporting the activity of Genasense in two types of blood cancer, multiple myeloma and a related disorder known as Waldenstrom¿s macroglobulinemia. Genasense, the company¿s lead antisense compound, is in several Phase III trials. Genasense shuts down production of a protein in cancer cells known as Bcl-2, believed to be a key factor in chemotherapy resistance. Prior studies have shown that Bcl-2 is overexpressed in many types of cancer, including multiple myeloma.
¿ Genentech Inc., of South San Francisco, and IDEC Pharmaceuticals Corp., of San Diego, examined the role of Rituxan (rituximab) in the treatment of immune thrombocytopenic purpura, an autoimmune disorder characterized by bruising and abnormal bleeding. Each of 23 patients received 375 mg/m2 of Rituxan weekly for four weeks. Response was defined as a platelet increase of greater than 20,000/ul from baseline in order to achieve a platelet count greater than 30,000/ul for more than one month¿s duration, within 12 weeks of the first Rituxan infusion. To date, 47 percent of evaluable patients have responded to treatment with 38 percent achieving a complete response and 9 percent achieving a good response.
¿ Hemosol Inc., of Toronto, said the oxygen-carrying characteristics of Hemolink (hemoglobin raffimer) are similar to those of fresh blood. Hemolink is a highly purified natural protein. The study was conducted in vitro, using a cardiopulmonary bypass circuit, a device used during cardiac surgery to regulate blood and oxygen flow. The circuit was primed with either the deoxygenated form of Hemolink mixed with human plasma, or diluted, anticoagulated fresh whole human blood. As the mixture flowed, samples were taken. Researchers found no difference between the oxygenated and deoxygenated cycles of Hemolink, the same result seen with whole human blood.
¿ Human Genome Sciences Inc., of Rockville, Md., reported the results of three preclinical studies. In one, investigators concluded that mirostipen exhibits a positive effect on the protection of long-term repopulating bone marrow hematopoietic stem cells, supporting continued development of mirostipen as a potential treatment for accelerating recovery from chemotherapy-induced myelotoxicity. Other results showed rapid and specific targeting to lymphoid tissues and B-cell tumors with administration of a radiolabeled BLyS, supporting further evaluation of a radiolabeled BLyS protein to treat B-cell cancers, such as non-Hodgkin¿s lymphoma and multiple myeloma. The third study suggests implementing a prophylactic regimen in ongoing repifermin clinical trials, which are evaluating keratinocyte growth factor-2¿s potential to treat cancer therapy-induced mucositis.
¿ Immunomedics Inc., of Morris Plains, N.J., said its yttrium-90-radiolabeled anti-CD22 humanized antibody (90Y-epratuzumab), currently in development, can be given repeatedly without any adverse immunological effects. The antibody drug has been studied in patients with various types of non-Hodgkin¿s lymphoma relapsing or resistant to standard chemotherapy. Twenty-one patients were enrolled, with 19 evaluated who received two, three or four weekly injections of the radiolabeled, humanized antibody. The treatment regimen could be repeated once after three months, provided there was neither severe toxicity nor progression of disease.
¿ Millennium Pharmaceuticals Inc., of Cambridge, Mass., said preliminary findings from an ongoing Phase II trial of LDP-341 in patients with multiple myeloma who have failed to respond to other treatments showed that LDP-341 halted the progression of the disease in nearly all study participants while reducing a primary marker of cancer severity in a significant number of patients. Also, those receiving therapy experienced manageable side effects.
¿ Novartis AG, of Basel, Switzerland, reported that its Gleevec (imatinib mesylate) in newly diagnosed patients with chronic myeloid leukemia (CML) in the early chronic phase results in high cytogenetic response rates. Complete cytogenetic response, the elimination of the cancer cells that characterize CML, is the ultimate goal. The rates reported are significantly higher than those historically documented with other CML therapies in the same disease setting. Of 47 newly diagnosed patients tested after three months of treatment, 77 percent achieved complete or major cytogenetic responses. The hematologic response rate (normalization of blood counts lasting for at least four weeks) was 98 percent.
¿ Novuspharma SpA, of Bresso, Italy, said results from a full analysis of data from a single-agent, Phase II trial with its lead product, BBR 2778, for non-Hodgkin¿s lymphoma indicated that it is effective as a monotherapy in patients with relapsed, aggressive NHL. Nine of 33 patients responded to treatment, with five showing a complete tumor response (defined as complete disappearance of all lesions) and four others showing a partial response (defined as a reduction in lesion size of at least 50 percent).
¿ SuperGen Inc., of Dublin, Calif., reported data from a Phase II study of its anticancer drug pentostatin (Nipent) showing a 60 percent overall response rate in treating patients with refractory chronic graft-vs.-host disease. Ten evaluable patients, all of whom failed at least one prior immunosuppressive regimen, were given Nipent every two weeks for three months. The overall response rate was 60 percent ¿ five complete responses and one partial response. One had a mixed response and three progressed with disease. Major responses were observed in all organ systems, including the liver.
¿ V.I. Technologies Inc., of Watertown, Mass., said results of a Phase II study for its Inactine Pathogen Inactivation System for red cells demonstrated for the first time that full units of Inactine-treated red cells could be safely reinfused into healthy volunteers after 42 days of storage. The study included 48 healthy adult volunteers and evaluated the safety and maximum storage time of a full unit of red blood cells treated with Inactine for 24 hours vs. untreated red blood cells. The Inactine-treated red blood cells met the regulatory requirement for greater than 75 percent recovery after 24 hours post-infusion and less than 1 percent hemolysis following 42 days of storage.