By Karen Pihl-Carey

Monoclonal antibodies and their efficacy in treating non-Hodgkin's lymphoma (NHL) have taken center stage at the 41st annual meeting of the American Society of Hematology (ASH) in New Orleans.

The three stars are Coulter Pharmaceutical Inc.'s Bexxar, and two IDEC Pharmaceuticals Corp. drugs, the already-approved Rituxan and the up-and-coming Zevalin.

Preliminary results of a Phase III trial indicate therapy with Zevalin (ibritumomab tiuxetan, IDEC-Y2B8) plus Rituxan in patients with relapsed or refractory, low-grade, follicular or transformed CD20-positive, B-cell NHL provides a greater benefit than does therapy with Rituxan alone.

"The study showed that Zevalin plus Rituxan got an overall response rate of 80 percent, while Rituxan alone got a response rate of 44 percent," said Vince Reardon, spokesman for San Diego-based IDEC. "We were pretty encouraged about that. We are seeking to submit a BLA [biologics license application] by mid-next year."

Reardon added a product launch could occur in 2001.

In the multi-center, randomized, controlled study involving 90 patients, those receiving combination therapy showed a 59 percent partial response and a 21 percent complete response. In terms of toxicity, 25 percent of Zevalin patients experienced Grade 4 neutropenia and 6 percent experienced Grade 4 thrombocytopenia. Patients recovered in a median of 14 and 12 days, respectively, indicating the toxicity is reversible.

Connie Matsui, vice president of planning and resource development at IDEC, said Zevalin and Rituxan complement each other, with the first being a versatile drug suitable for various stages of lymphoma, and the second being a more aggressive therapy for later-stage lymphoma. Matsui also noted the data are just what the FDA is looking for.

"The efficacy that was reported in this interim analysis bodes well for meeting FDA's requirements for product approval," she told BioWorld Today. "The FDA was looking for a certain spread between Rituxan efficacy and Zevalin efficacy, and the results reported thus far certainly meet that criteria, if not exceed it."

Also, in a Phase II trial evaluating safety and efficacy of Zevalin in NHL patients with mild thrombocytopenia, five patients achieved a complete response and 10 achieved a partial response, out of 22 evaluable patients total. And in a non-randomized, controlled, open-label Phase III trial evaluating safety and efficacy of Zevalin in follicular NHL patients who are refractory to Rituxan, about 46 percent of patients achieved a partial response.

Rituxan, indicated for the treatment of patients with relapsed or refractory, low-grade or follicular, CD20 positive, B-cell NHL, will move into a Phase III study in patients with intermediate- or high-grade NHL, based on positive Phase II data. IDEC and its marketing partner, Genentech Inc., of South San Francisco, plan to begin the safety and efficacy trial, a randomized, open-label study, in January.

In a Phase II trial evaluating Rituxan plus CHOP (cyclophosphamide, doxorubicin, vincristine and prednisone) chemotherapy in low-grade NHL, 22 patients achieved complete responses and 13 patients achieved partial responses, out of 35 evaluable patients. Sixty-three percent of patients have been in remission for 36 months or more.

In another Phase II trial in intermediate- or high-grade NHL, the overall response rate was 97 percent, with 20 patients achieving complete responses and 12 achieving partial responses. Adverse events of Rituxan plus CHOP were Grade III and IV neutropenia, similar to what was observed with CHOP chemotherapy alone.

Researchers said South San Francisco-based Coulter Pharmaceutical Inc.'s Bexxar (tositumomab, iodine I 131 tositumomab), when added to fludarabine, seemed to increase the complete response rate five-fold in patients with low-grade or follicular NHL. The Phase II safety and efficacy study looked at 14 evaluable patients, in which two achieved a complete response after initial treatment. At the 13th week of treatment, six experienced a complete response, and at six months, 10 did.

Also in five Phase I-III trials, 81 percent of patients with low-grade NHL responded to Bexxar, with 39 percent experiencing a complete response, compared to 52 percent who had responded to their last chemotherapy, with 14 percent experiencing a complete response. A long-term follow-up showed a median duration of complete remission of 57 months.

In a combined analysis of Bexxar in transformed low-grade NHL, 53 percent of patients elicited a response, with 29 percent experiencing complete remission. The median duration of complete response was 20 months.

And in four Phase I-III trials of 14 small lymphocytic lymphoma patients, nine patients responded to the therapy with three experiencing a complete remission.

Deutsche Banc Alex. Brown, of New York, estimated Bexxar sales could be $36 million, $168 million and $225 million in 2000, 2001 and 2002, respectively.

Coulter stock (NASDAQ:CLTR) closed Monday at $18.75, up $1.875, while IDEC's stock (NASDAQ:IDPH) closed at $113.50, down $13.312.

Also at the ASH conference:

¿ Avigen Inc., of Alameda, Calif., said its gene therapy to treat hemophilia B is showing benefit. After delivering the gene for factor IX using Avigen's adeno-associated vector, factor IX protein activity was detected in the blood of the initial hemophilia patients treated, even at the lowest dose administered.

¿ Celgene Corp., of Warren, N.J., said a Phase II trial of Thalomid (thalidomide) in patients with advanced and refractory multiple myeloma showed 36 percent of patients achieved a 25 percent or more reduction in tumor burden. Eighteen patients achieved paraprotein response of 90 percent or more, and four patients achieved a complete response.

¿ Cerus Corp., of Concord, Calif., said data from a preclinical study of its proprietary allogeneic cellular immune therapy (ACIT) system demonstrated that transfusion of S-59 treated T-cells facilitated bone marrow engraftment and long-term survival without graft-vs.-host disease.

¿ Dendreon Corp., of Seattle, said clinical data of two Phase I/II trials of its immunotherapy product for multiple myeloma show the drug appears safe, well tolerated and causes tumor regressions in some patients. Of 38 evaluable patients whose disease was resistant to standard or high-dose chemotherapy, about 45 percent had minor responses or stabilization of their disease, and half of all patients had stable disease for more than 39 weeks.

¿ Eligix Inc., of Medford, Mass., said BCell-HDM, a tumor cell-targeting device, removed B-cells from the transplant cell dose in nine patients with relapsed B-cell non-Hodgkins lymphoma. The patients had undergone high-dose chemotherapy followed by autologous stem cell transplantation.

¿ Fred Hutchinson Cancer Research Center, of Seattle, said in a study of cancer patients transplanted with marrow vs. stem cells, the stem cells may offer fewer relapses with fewer complications. The two-year survival rate among the marrow transplant patients was 45 percent, compared with the rate of 70 percent for the stem cell patients.

¿ Immunomedics Inc., of Morris Plains, N.J., said interim results of its Phase I/II trial of Epratuzumab to treat non-Hodgkin's lymphoma show potential efficacy similar to other antibody products, but with a minimal toxicity. Almost 70 percent of patients enrolled achieved partial and complete remissions at the optimal intravenous doses given weekly over four weeks.

¿ Inex Pharmaceuticals Corp., of Vancouver, British Columbia, said results from a Phase IIa trial of Onco TCS demonstrated the drug is effective in shrinking tumors in patients with relapsed non-Hodgkin's lymphoma. Out of 68 total evaluable non-Hodgkin's lymphoma patients, 38 with aggressive NHL had a 45 percent response rate and 12 with transformed NHL had a 42 percent response rate. The other 18 patients had other types of NHL and did not experience a significant response to treatment. Inex is starting a pivotal Phase II/III trial of Onco TCS as a treatment for second-relapsed aggressive NHL. (See BioWorld Today, Oct. 4, 1999, p. 1.)

¿ IntraBiotics Pharmaceuticals Inc., of Mountain View, Calif., said Phase II results of Protegrin IB-367 show patients who received the compound experienced a significant reduction in the severity of oral mucositis. The drug was generally well tolerated in the randomized, placebo-controlled study of 177 patients. Investigators reported the drug reduced average post-transplant mucositis by 22 percent . In patients who received the drug four or more days before transplantation, it reduced mucositis severity by 40 percent.

¿ Oncosis, of San Diego, said its new instrument-based methodology locates and purges every detectable tumor cell in a stem cell transplant. The approach integrates automated scanning cytometry, image analysis and laser-induced necrosis to kill all detectable target cells. The method is potentially valuable in autologous stem cell transplants to preserve the stem cell population and eliminate cancer cells, the company said, because other cells in a sample are left undisturbed.

¿ SuperGen, of San Ramon, Calif., said five patients in a Phase I trial of Nipent (pentostatin) at the Johns Hopkins Oncology Center in Baltimore responded to the therapy, suggesting it could have benefit in graft-vs.-host disease. The study's principal investigator, Jeffrey Margolis, also reported there was no significant toxicity attributed to the drug.

¿ Targeted Genetics Corp., of Seattle, said it obtained the option to license exclusive rights to proprietary technology from the University of North Carolina at Chapel Hill related to the treatment of hemophilia A via gene delivery. The company intends to use the technology to develop an adeno-associated virus vector approach to treat the disease. Financial terms were not disclosed.