Genentech Inc. presented data on extended therapy with Rituxan, partnered with IDEC Pharmaceuticals Corp., at the 44th annual meeting of the American Society of Hematology in Philadelphia.
The trial examined Rituxan (MabThera/rituximab) in patients with indolent non-Hodgkin's lymphoma and demonstrated that extended single-agent Rituxan therapy reduced the risk of disease progression or relapse by 55 percent for responding patients and nearly doubled event-free survival for chemotherapy-naive indolent NHL patients.
The study involved 202 patients, 185 of whom were evaluable. All patients were given an induction course of Rituxan, and 67 percent of chemotherapy-naive patients responded while 46 percent of those with relapsed disease responded. At week 12, 80 percent of evaluable patients had achieved a complete response, a partial response or stable disease.
From that point, patients were randomized to receive either extended therapy with Rituxan or did not receive further therapy. After a median of 35 months, the primary endpoint of event-free survival was a median of 23 months in patients who received extended Rituxan therapy, compared to 12 months for patients who did not receive extended therapy and were observed. The difference in event-free survival was greater in chemotherapy-naive patients than previously treated patients. Event-free survival for the chemotherapy-naive patients receiving extended Rituxan therapy was 36 months, compared to 19 months for patients who were not given extended treatment.
For responding patients at week 12, 56 percent of patients in the observation arm and 80 percent of patients who received extended Rituxan therapy were in remission one year after initiation of the study.
Genentech also presented five-year follow-up data from a Phase II study of Rituxan plus CHOP (cyclophosphamide, doxorubicin, vincristine and prednisone) chemotherapy in aggressive front-line NHL. Thirty-three patients received six cycles of both Rituxan and CHOP.
The initial analysis reported a 97 percent overall response rate, with 61 percent of patients experiencing a complete response and 36 percent having a partial response. At 26 months median follow-up, 91 percent were alive and 88 percent were free of disease progression.
After more than five years of follow-up, 88 percent of patients were alive and 81 percent of patients were free from disease progression, South San Francisco-based Genentech said.
Rituxan is indicated as a single-agent treatment for relapsed or refractory low-grade or follicular, CD20-positive, B-cell NHL. MabThera, in combination with CHOP chemotherapy, received European approval to treat aggressive NHL in March 2002. Genentech and IDEC co-market Rituxan in the U.S., while F. Hoffmann-La Roche Ltd, of Basel, Switzerland, markets it in the rest of the world, except Japan, where Roche and Zenyaku Kogyo Co. Ltd. co-market the drug.
IDEC, of San Diego, separately reported results from a Phase I/II study of IDEC-114 in relapsed or refractory, follicular non-Hodgkin's lymphoma patients. Data are available on the first 22 patients with a median follow-up of two months. Tumor burden reductions have been observed at all doses, IDEC said, including a 19 percent objective response rate at 375 mg/m2 (three complete responses and no partial responses in 16 patients). Also, there were no dose-limiting toxicities or serious adverse events, with the most commonly reported adverse events being fatigue in 26 percent of patients and nausea in 9 percent of patients. Ongoing studies are evaluating higher doses of the antibody and in combination with Rituxan.
Genentech's stock (NYSE:DNA) fell 82 cents Tuesday to close at $33.18. IDEC's stock (NASDAQ:IDPH) rose 81 cents to close at $34.13. In other news from the meeting:
• Amgen Inc., of Thousand Oaks, Calif., presented results from a study in which Aranesp (darbepoetin alfa) was shown to be 13 percent less expensive than epoetin alfa while demonstrating comparable response rates for the treatment of anemia in chemotherapy patients, based on the average wholesale prices of Aranesp and epoetin alfa over a 20-week period, the company said. Epoetin alfa is currently marketed by Amgen as Epogen and by Ortho Biotech Products LP as Procrit.
• Celgene Corp., of Warren, N.J., reported that nine of 16 evaluable patients, or 56 percent, with myelodysplastic syndromes responded to Revimid (CC-5013) therapy, including five patients with deletion of chromosome 5q31-33 who achieved a complete cytogenetic response. Revimid is from the ImiD pipeline of drugs, which are small-molecule, orally available compounds that modulate the immune system. The company also reported data from a clinical trial of Thalomid (thalidomide) in combination with prednisone in myelofibrosis. The data demonstrated that 13 of 21 patients achieved an objective clinical response that was defined by an increase in red blood cells or platelets. The data are scheduled to be published in an upcoming issue of Blood. Celgene is initiating pivotal trials of Thalomid in newly diagnosed multiple myeloma and metastatic renal cell cancer.
• Cell Therapeutics Inc., of Seattle, presented data on Trisenox in myelodysplastic syndrome. In a Phase II 42-patient single-agent study of Trisenox, low- and high-risk patients with the affliction were treated with Trisenox for two weeks on and two weeks off until disease progression or toxicity. Patients tolerated the drug well with up to 10 cycles of treatment being administered. Of the 32 evaluable patients, 11 showed objective responses and 12 showed stable disease. Trisenox (arsenic trioxide) was approved for marketing in 2000 by the FDA to treat patients with relapsed or refractory acute promyelocytic leukemia.
• Emisphere Technologies Inc., of Toronto, said results of its "Protect" Phase III trial evaluating a liquid oral heparin demonstrated for the first time in patients that heparin could be delivered safely and effectively into the bloodstream in an oral form. The company also reported that a study evaluating two solid oral heparin formulations, in tablet and capsule form, in healthy male volunteers showed that an effect on blood coagulation was achieved consistent with heparin blood levels deemed acceptable for prevention of deep vein thrombosis, without any tolerability issues. The solid doses made use of Emisphere's eligen oral drug delivery technology.
• EntreMed Inc., of Rockville, Calif., reported preclinical data demonstrating the increased activity of its thalidomide analogue, ENMD 0995, when compared to thalidomide and other thalidomide analogues, in preclinical and animal models of multiple myeloma, a form of blood cancer. In the studies, ENMD 0995 also exhibited less toxicity and greater activity against other tumor types, including lung carcinoma and glioblastoma, an aggressive variety of brain cancer, the company said. ENMD 0995 is in Phase I trials and has been granted orphan drug status from the FDA.
• Genta Inc., of Berkeley Heights, N.J., presented two studies that support the activity of Genasense in two types of plasma cell cancers known as multiple myeloma and Waldenstrom's macroglobulinemia. The first study reported preliminary results using Genasense in combination with a standard chemotherapy regimen called "VAD" - vincristine, adriamycin and high-dose dexamethasone. In a second preclinical study, Genasense was evaluated in experiments using human cells of Waldenstrom's macroglobulinemia. Genasense works by inhibiting the production of Bcl-2.
• Genzyme Molecular Oncology, of Framingham, Mass., a division of Genzyme Corp., presented data from a Phase I/II breast cancer vaccine trial. The vaccine used in the trial was produced using a cell fusion technology in which cancer cells surgically removed from the patient are chemically combined with dendritic cells. Ten patients with late-stage, pretreated metastatic breast cancer were vaccinated in the open-label study. Two patients showed measurable tumor regressions following the vaccine therapy. A third patient with metastatic disease confined to the bones and chest wall lining also showed stable disease six months following vaccination.
• Ilex Oncology Inc., of San Antonio, developed Campath (alemtuzumab), and the drug was the subject of several presentations made by independent investigators. Niguarda Ca Granda Hospital reported subcutaneously administered alemtuzumab in 12 B-cell chronic lymphocytic leukemia patients with minimal residual disease following response to treatment with fludarabine phosphate showed the therapy to be effective and safe. The University of Cologne, Germany, presented data on 11 patients from an ongoing Phase II trial. The trial of combination fludarabine phosphate and alemtuzumab therapy in patients with relapsed/refractory B-cell chronic lymphocytic leukemia showed the therapy to have efficacy, with a mild and manageable safety profile, the university said. A study conducted by the Centre Hospitalier Lyon-Sud's Department of Hematology showed that a new follow-up regimen of alemtuzumab is superior to the standard alemtuzumab regimen in previously treated B-cell chronic leukemia and non-Hodgkin's lymphoma patients, as well as in T-prolymphocytic leukemia patients.
• NeoRx Corp., of Seattle, presented long-term follow-up data for multiple myeloma patients treated in a Phase I/II dose-escalation study of Skeletal Targeted Radiotherapy (STR) with high-dose chemotherapy and stem cell transplantation. STR is in development for multiple myeloma patients eligible for stem cell transplantation, with the goal of prolonging patient survival and event-free survival. Investigators concluded that STR appears to be an active agent in the treatment of multiple myeloma, providing a high complete response rate in combination with standard transplantation regimens. Separately, NeoRx reported results of a Phase I study of Pretarget Lymphoma in 15 patients with relapsed or refractory CD20-positive adult B-cell non-Hodgkin's lymphoma. Investigators said the Phase I data are encouraging. A Phase I study of Pretarget Carcinoma in patients with metastatic colorectal carcinoma led investigators to say the regimen was generally safe and well tolerated, with high tumor uptake of the radiotherapeutic relative to other organs and less bone marrow exposure than is typically seen with directly radiolabeled antibody targeting agents.
• Novartis AG, of Basel, Switzerland, reported data from the first head-to-head study of Gleevec (imatinib meyslate) and said that chronic myeloid leukemia patients treated with Gleevec are less likely to show progression to advanced disease than those taking an interferon-based regimen and are nine times more likely to achieve a complete cytogenetic response. Gleevec is indicated for the treatment of patients with Ph+ CML in blast crisis, accelerated phase, or in chronic phase after failure of interferon-alpha therapy. Novartis also presented data suggesting a once-daily oral dose of ICL670, an iron-chelating drug, might replace Desferal (deferoxamine mesylate for injection), which is usually administered via a continuous infusion over eight to 12 hours, the company said. The data were from an ongoing Phase II study in 71 patients with thalassemia.
• Peregrine Pharmaceuticals Inc., of Tustin, Calif., presented preclinical data showing that nonradiolabeled Lym-1 antibodies had a significant antitumor effect on several B-cell lymphoma cancer models. The study revealed that Lym-1 had activity when human natural killer cells were present in the mouse models, indicating that Lym-1 might interact with the immune system to provide an antitumor effect. The Lym-1 antibody is a murine IgG2a monoclonal antibody raised against Raji cells, a malignant line cultured from Burkitt's lymphoma.
• Vion Pharmaceuticals Inc., of New Haven, Conn., reported data on its anticancer agent, Triapine, in two Phase I trials. A total of 44 patients with advanced hematologic malignancies that had progressed following one or more standard treatments were entered into the two trials and Triapine was demonstrated to be well tolerated. Approximately 60 percent of patients had a greater than 80 percent reduction in the number of circulating leukemia cells, and about 40 percent had a greater than 95 percent temporary reduction. Triapine is designed to be an inhibitor of ribonucleotide reductase. The product is licensed from Yale University.