Fractionated Radioimmunotherapy With (90)Y-epratuzumab in Non-Hodgkin's Lymphoma Appears Safe and Active in a Phase I/II Study
- Category: Antibodies
- Published on Tuesday, 12 June 2007 04:00
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VIENNA, Austria | June 11, 2007 | Immunomedics, Inc.(Nasdaq: IMMU), a biopharmaceutical company focused on developingmonoclonal antibodies to treat cancer and other serious diseases, todayannounced that data presented at the 12th Congress of EHA in Vienna,Austria, showed positive responses in patients with non-Hodgkin's lymphoma(NHL) treated with a new radioimmunotherapy (RAIT) using epratuzumab todeliver toxic radiation directly to lymphoma cells in small fractions.Franck Morschhauser, MD, Centre Hospitalier Regional Universitaire deLille, Lille, France, is the lead investigator of this open-label,multicenter Phase I/II dose-escalation study and the presenter at themeeting.
Current RAIT treatments for NHL such as tositumomab and ibritumomabtiuxetan are radiolabeled murine antibodies targeting the CD20 antigen onthe surface of mature B-cells and B-cell tumors as expressed by NHL cells.Immunomedics' epratuzumab is a humanized monoclonal antibody that targetsthe CD22 antigen on B-cells, including malignant B-cells. The internalizingproperty of epratuzumab is believed to be well suited for deliveringradiation from the potent radioisotope, yttrium-90, selectively and locallyto lymphoma cells that express the CD22 antigen. Moreover, becauseepratuzumab is humanized, it is argued that the new RAIT can beadministered to patients repeatedly in smaller doses. Researchers foundthat splitting the dose over two or three fractions made it tolerable topatients while delivering higher radioactivity to tumor cells.
At the time of reporting, 54 patients were evaluated with an overallobjective response rate of 59% and a complete response rate of 43%.Moreover, responses appear durable with 6 complete responders who remaineddisease free for more than 1 year, including 4 continuing for more than 2years. Both the objective and complete response rates appear to increasewith higher cumulative doses. Objective responses occurred for 41% ofpatients at the lowest total doses of 5-10 mCi/m(2), compared to 55% in thegroups receiving 15-20 mCi/m(2), 63% in the 22.5-37.5 mCi/m(2) cohorts, and90% receiving the highest cumulative doses of 37.5-45 mCi/m(2). Similarly,complete responses occurred for 29% of patients in the 5-10 mCi/m(2) totaldose groups, compared to 45% at 15-20 mCi/m(2), 44% at 22.5-37.5 mCi/m(2),and 60% at 37.5-45 mCi/m(2).
Importantly, 64% of patients who had received priorrituximab-containing regimens responded to (90)Y-epratuzumab, as well as41% of patients with prior bone marrow transplant. Moreover, responses wereseen in patients with different types of NHL. Sixty-eight percent ofpatients with follicular lymphoma responded to the RAIT, compared to 57%for mantle cell lymphoma, 22% for diffuse large B-cell lymphoma, and all 3patients with marginal zone lymphoma.
"We are very encouraged by these results. Not only did we observe highresponse rates but, more importantly, the responses were seen in patientswith different types of NHL, and in rituximab-treated or naïve patientswith or without a history of bone marrow transplants," remarked Dr. FranckMorschhauser.
Adult patients with documented B-cell NHL who failed at least one priorregimen of standard chemotherapy were eligible for this study. At the timeof reporting, 58 patients with a median of 3 prior therapies have completedtreatment. Patients were treated once weekly for two or three consecutiveweeks and the (90)Y dose was escalated in successive patient cohorts. Forpatients with prior bone marrow transplants, dose escalation stopped at 10mCi/m(2) total dose (5.0 mCi/m(2) x 2 weeks). For patients without priorbone marrow transplants, however, the study is continuing at the highesttested level of 45 mCi/m(2) total dose (15.0 mCi/m(2) x 3 weeks).
"We are particularly enthused by the strong safety profile, which webelieve allows us to increase the radiation dosage needed to achieve moreeffective results. The 45 mCi/m(2) cumulative dose level is more thantwo-fold higher than the maximum allowable dose of 32 mCi for ibritumomabtiuxetan, or 18.5 mCi/m(2) based on a body area of 1.73 m(2) for a standardperson," commented Cynthia L. Sullivan, President and Chief ExecutiveOfficer. "This study is now almost completed, and we will decide to eitherout-license this agent, or complete the clinical development on our own,"she added.
Immunomedics is a New Jersey-based biopharmaceutical company focused onthe development of monoclonal, antibody-based products for the targetedtreatment of cancer, autoimmune and other serious diseases. We havedeveloped a number of advanced proprietary technologies that allow us tocreate humanized antibodies that can be used either alone in unlabeled or"naked" form, or conjugated with radioactive isotopes, chemotherapeutics ortoxins, in each case to create highly targeted agents. Using thesetechnologies, we have built a pipeline of therapeutic product candidatesthat utilize several different mechanisms of action. We have licensed ourlead product candidate, epratuzumab, to UCB, S.A. for the treatment of allautoimmune disease indications worldwide. We have retained the rights forepratuzumab in oncology indications for which UCB has been granted a buy-inoption. UCB has development, manufacture and commercialization rights, andis responsible for all clinical trials evaluating epratuzumab for thetreatment of patients with moderate and severe lupus. At present, there isno cure for lupus and no new lupus drug has been approved in the U.S. inthe last 40 years. The Company is conducting clinical trials with hA20 inpatients with non-Hodgkin's lymphoma, epratuzumab as a potentialtherapeutic for patients with lymphoma and leukemia, (90)Y-epratuzumab forthe therapy of patients with lymphoma, (90)Y- hPAM4 for pancreas cancertherapy and hCD74 as a therapy for patients with multiple myeloma. Webelieve that our portfolio of intellectual property, which includesapproximately 108 patents issued in the United States, and more than 250other issued patents worldwide, protects our product candidates andtechnologies. We also have a majority ownership in IBC Pharmaceuticals,Inc., which is developing a novel Dock and Lock (DNL) methodology, and anew method of delivering imaging and therapeutic agents selectively todisease, especially different solid cancers (colorectal, lung, pancreas,etc.), by proprietary, antibody-based, pretargeting methods. For additionalinformation on us, please visit our web site athttp://www.immunomedics.com. The information on our website does not,however, form a part of this press release.
This release, in addition to historical information, may containforward- looking statements made pursuant to the Private SecuritiesLitigation Reform Act of 1995. Such statements, including statementsregarding clinical trials, out-licensing arrangements (including the timingand amount of contingent payments), forecasts of future operating results,and capital raising activities, involve significant risks and uncertaintiesand actual results could differ materially from those expressed or impliedherein. Factors that could cause such differences include, but are notlimited to, risks associated with new product development (includingclinical trials outcome and regulatory requirements/actions), ourdependence on our licensing partner for the further development ofepratuzumab for autoimmune indications, competitive risks to marketedproducts and availability of required financing and other sources of fundson acceptable terms, if at all, as well as the risks discussed in theCompany's filings with the Securities and Exchange Commission. The Companyis not under any obligation, and the Company expressly disclaims anyobligation, to update or alter any forward-looking statements, whether as aresult of new information, future events or otherwise.
SOURCE: Immunomedics, Inc.