ImClone Systems Inc. presented preclinical data from an Erbitux study in human colorectal carcinoma xenografts at the 93rd annual meeting of the American Association for Cancer Research in San Francisco.
ImClone researchers reported on the use of Erbitux as a single-agent therapy and in combination with the three-drug chemotherapy regimen of irinotecan, 5-FU and leucovorin in two models. The data showed that treatment with Erbitux plus the three-drug regimen inhibited the growth of the xenografts in comparison to controls. Also, the combination of Erbitux and the regimen showed stronger antitumor activity when compared to just the three-drug regimen or to Erbitux alone. The combination also showed tumor necrosis, decreased tumor cell proliferation and increased tumor cell apoptosis.
ImClone CEO Harlan Waksal said in a prepared statement that the presented results “suggest the potential of Erbitux in combination [with the regimen] in treating colorectal cancer, and are consistent with previous studies demonstrating the potential antitumor activity of Erbitux when combined with chemotherapeutic drugs.”
ImClone is in the process of attempting to amend its rolling biologics license application for Erbitux to treat colorectal cancer. The drug is designed to target and block the epidermal growth factor receptor.
In other news from the meeting:
AltaRex Corp., of Waltham, Mass., made an oral presentation of clinical results from an integrated analysis of two OvaRex studies in recurrent ovarian cancer. The company discussed data regarding T-cell activation and correlated clinical benefit. In the reported studies, OvaRex was active in recurrent disease, tumor burden did not impact the frequency or quality of immune responses and OvaRex was able to induce cellular responses to CA125 and autologous tumor cells, the company said.
Ariad Pharmaceuticals Inc., of Cambridge, Mass., reported studies on its orally active drug candidate for cancer, AP23573, saying it demonstrated tumor shrinkage through metabolic arrest and inhibition of nutrient uptake in tumors leading to cancer-cell starvation. Animals with implanted tumors treated with AP23573 at low doses for five days showed reduction in tumor volume even after termination of treatment.
Arius Research Inc., of Toronto, reported additional preclinical third-party research that showed a reduction in metastases and tumor size for mice treated with Arius’ monoclonal antibody, ARH460-23, compared to controls. Also, Arius released information on the antigen target for ARH460-23, confirming that it is cancer related. ARH460-23 was studied in human lung cancer that had been implanted in the lungs of mice.
AVI BioPharma Inc., of Portland, Ore., presented research data on the use of Neugene antisense technology against prostate cancer. The presentation showed that the technology, when directed against the c-myc gene, caused cell growth inhibition and cell death in human prostate cancer cells in athymic mice. The study demonstrated the feasibility of developing AVI-4126 as a single agent or in combination therapy for locally relapsed and metastatic prostate cancer in patients. AVI-4126 is a Neugene antisense drug.
Celgene Corp., of Warren, N.J., presented data from preclinical studies of IMiDs (Immunomodulatory Drugs) and SelCIDs (Selective Cytokine Inhibitory Drugs). The data demonstrated that IMiDs and SelCIDs have antitumor effects in in vivo models of solid tumor cancers. Celgene scientists and collaborators evaluated the ability of IMiDs to enhance the antitumor effects of an experimental cancer vaccine. Pretreatment with IMiDs enhanced the antitumor immunity of vaccinated mice both after the initial challenge with live tumor cells and after a second challenge 60 days later. The data indicated that IMiDs have the potential to provide long-lasting enhancement of novel cancer therapies. Also, Celgene scientists evaluated the anticancer properties of several SelCIDs. The SelCIDs inhibited the proliferation of cancer cells and caused apoptosis in a dose-dependent manner in preclinical models of colorectal, prostate and melanoma cancers.
Cell Therapeutics Inc., of Seattle, presented in vitro data on the metabolism of polyglutamate paclitaxel. By identification of intermediates made up of paclitaxel bound to one or two glutamic acid residues, the study concluded that proteolytic enzymes are important for biodegradation of PG-TXL by the tumor cell. The study also concluded that the release of free paclitaxel might be increased in tumors as a result of metabolism by cathepsin B. PG-TXL is a pharmaceutical that links to paclitaxel, the active ingredient in Taxol.
CuraGen Corp., of New Haven, Conn., said its scientists discovered a gene, CG57067, that codes for a protein (designated Angioarrestin) capable of inhibiting angiogenesis. CuraGen scientists are investigating this protein as a potential therapeutic to inhibit angiogenesis for the treatment of cancer.
Dendreon Corp., of Seattle, presented data that confirm the antigen target of Provenge, prostatic acid phosphatase (PAP), is highly expressed in prostate cancer. An analysis performed on subjects screened for enrollment in the trial program for Provenge demonstrated that PAP was expressed in more than 95 percent of unique prostate cancer tumor specimens on a sufficient percent of cells to warrant study inclusion and therapy with Provenge. Provenge is Dendreon’s investigational therapeutic vaccine in Phase III development for prostate cancer.
EntreMed Inc., of Rockville, Md., released new preclinical findings showing that Endostatin inhibits B16 melanoma from metastasizing to the liver. EntreMed presented the preclinical data, along with data from Phase I trials, to the FDA for consideration of Endostatin to receive orphan drug status for the treatment of patients with malignant metastatic melanoma. The FDA granted the status in February. Endostatin is in four Phase I and Phase II clinical trials. Separately, the company released preclinical findings discovered by its in-house scientific team on EntreMed’s drug candidate, Panzem. In a preclinical study, scientists found that Panzem kills tumor cells and the supporting blood vessel cells by turning on increased levels of a death receptor (death receptor 5) located on the cell surface, to trigger apoptosis. Additionally, the team concluded that death receptor 5 may serve as a surrogate marker for assessing clinical responses to Panzem.
Genta Inc., of Berkeley Heights, N.J., presented preclinical data that showed Genasense, its antisense drug, effectively killed leukemia cells that had developed resistance to Gleevec (imatinib mesylate; Novartis Inc., of Basel, Switzerland). In a new study commissioned by Genta, investigators from the University of Tokyo evaluated the effects of Genasense in Gleevec-resistant CML cells. Whereas Gleevec alone was ineffective in this model, Genasense treatment produced a marked antileukemic response, with most cells showing an increase in apoptosis. Also, Genasense treatment was associated with superior survival compared with Gleevec, the company said. Genasense is in late-stage, Phase III testing in multiple clinical indications.
Geron Corp., of Menlo Park, Calif., reported positive preclinical data from separate studies of three anticancer product candidates under development. The studies demonstrated antitumor activity without toxicity for all three approaches. Together, those studies confirm the effectiveness of inhibiting or targeting telomerase in the treatment of cancer, the company said. Geron’s portfolio of telomerase-based anticancer therapies includes GRN163, a telomerase inhibitor; a telomerase promoter-driven oncolytic virus; and ex vivo and in vivo telomerase vaccines.
Immunomedics Inc., of South San Francisco, reported on the progress with various technologies, including an antibody labeled with iodine-131 by its patented method that could achieve better therapeutic effects in animals with transplanted human breast cancer than the same antibody labeled with I-131 by conventional methods. Also, a presentation was made on a second antibody developed by Immunomedics, one that targets CD74, an antigen expressed on lymphoma, myeloma and melanoma cells. The naked antibody demonstrated cell-killing properties with non-Hodgkin’s lymphoma cells, and also has the property of rapid internalization into tumor cells.
Inex Pharmaceuticals Corp., of Vancouver, British Columbia, reported that its liposomal TCS drug delivery system improved the tumor inhibition activity of the approved cancer drugs vincristine, vinblastine and vinorelbine in preclinical studies. Vincristine is the active drug in Inex’s lead targeted chemotherapy product, Onco TCS, currently in a pivotal Phase II/III trial. Vinblastine and vinorelbine are being evaluated for encapsulation in the company’s TCS technology to form a new cancer drug for development.
Kosan Biosciences Inc., of Hayward, Calif., will make two poster presentations, both of which highlight advances in its ongoing development of the anticancer compound, KOS-862 (Epothilone D). Epothilones are polyketide natural products that inhibit cancer cells by the same mechanism as paclitaxel, and also are effective against paclitaxel-resistant tumors. In 2001, Kosan initiated a Phase I study of Epothilone D in patients with advanced solid tumors.
NeoPharm Inc., of Lake Forest, Ill., presented two studies as scientific posters with data suggesting that LErafAON may enhance the therapeutic effects of radiation therapy and also chemotherapy. Institutions are conducting ongoing preclinical and clinical studies on LErafAON in various solid tumors in combination with radiation therapy and chemotherapy, along with other studies at other medical centers. The studies were supported by funds from NeoPharm.
Oxigene Inc., of Watertown, Mass., presented preclinical data from its vascular targeting agent, Oxi-4503, saying that in a mouse system, Oxi-4503 induced complete regression of human breast cancer. The preliminary results build on the clinical success of Oxigene’s lead vascular targeting agent, Combretastatin A4 Prodrug (CA4P), designed to attack tumor vasculature and thereby substantially shut down blood flow to the tumor. Oxigene completed Phase I trials of CA4P, and plans to initiate a Phase Ib combination study of the drug with a chemotherapeutic agent in the first half of 2002.
Peregrine Pharmaceuticals Inc., of Tustin, Calif., is presenting nine abstracts in poster and oral presentations. One demonstrates that externalized anionic phospholipids on tumor endothelium could potentially be used for tumor vessel targeting and imaging. This research is part of the company’s vascular targeting agent technology and provides the scientific basis for the development of antiphosphatidyl serine fully human monoclonal antibodies. Also, a study found that human liver-expression chemokine can serve as a new effector molecule for tumor necrosis therapy. The company’s lead anticancer drug, Cotara, is in a multicenter Phase II study for the treatment of brain cancer and enrollment initiation is anticipated for a multicenter, multinational Phase III brain cancer study sometime this quarter.