Idec Pharmaceuticals Corp. took another step toward commercialization of a second antibody product for certain forms of non-Hodgkin's B-cell lymphoma, with the presentation of preliminary and updated results from four studies at the 36th annual meeting of the American Society of Clinical Oncology in New Orleans.
Zevalin (britumomab tiuxetan; formerly IDEC-Y2B8) targets the CD20 cell-surface marker, found only on B cells, and adds the punch of the yttrium-90 radioisotope.
The CD20 target is the same as that of San Diego-based Idec's Rituxan (rituximab), which in November 1997 became the first anticancer monoclonal antibody to win FDA approval and has become, according to Idec, the most frequently used NHL regimen in the U.S. Sales hit $263 million in 1999 and continued to grow in the first quarter of 2000. Genentech Inc., of South San Francisco, is the product's U.S. marketing partner.
The new ASCO data included interim results from a Phase III trial comparing Zevalin to a standard course of Rituxan in patients who had no response to chemotherapy or a response with time to progression of less than six months. The response rate to Zevalin was 77 percent in such patients vs. 81 percent in chemotherapy-sensitive patients (p=0.49). "These interim results suggest that Zevalin may find especially important applications in treatment of patients who have become refractory or unresponsive to chemotherapy," said Thomas Witzig, the Mayo Clinic researcher who presented the data.
Below is a summary of results from the other three Zevalin studies presented at ASCO:
¿ A 179-patient dosimetry study found that radiation absorption in non-target organs was "well within a safe range" for patients receiving a standard dose (or a dose reduced 25 percent in patients with low platelet counts).
¿ In a safety trial analyzing infection risk, 32 percent of Zevalin-treated patients experienced Grade 4 neutropenia (neutrophil count below 500/mm3). Clinical infections of moderate or greater severity occurred in 21 percent of patients, and 16 of the 210 patients enrolled were hospitalized, primarily due to infection. The results were "not unusual for patients undergoing chemotherapy," said presenter Lee Gordon, a researcher at Northwestern University Medical School and the Robert H. Lurie Cancer Center in Chicago.
¿ A blood analysis of 74 patients showed a strong link between the product's clearance of bcl-2-positive cells from circulation and clinical response. Eighty-four percent of patients whose peripheral blood was clear of bcl-2 responded to therapy, while only 20 percent of patients without such clearance responded.
In other news from ASCO:
¿ Celgene Corp., of Warren, N.J., reported Thalomid (thalidomide) data from clinical studies in a variety of cancers, including multiple myeloma, Waldenstrom's macroglobulinemia (a disease related to myeloma) and renal cell carcinomas. Celgene held an investigators meeting at ASCO to discuss further clinical development strategies for Thalomid, which won FDA approval in July 1998 for cutaneous manifestations of leprosy known as erythema nodosum leprosum.
¿ Genta Inc., of Lexington, Mass., reported additional data on Genasense (G3139), this time as a combination therapy with Novantrone (mitoxantrone) in men with advanced prostate cancer. In the Phase I study, antitumor activity was observed in eight of 22 patients in which the measurement could be made. The safety profile was "excellent." Genasense is an antisense product targeting the bcl-2 protein, present at increased levels in more than 80 percent of men with hormone-refractory prostate cancer. Immunex Corp., of Seattle, markets Novantrone.
¿ Ligand Pharmaceuticals Inc., of San Diego, reported data Phase II trial data for Targretin (bexarotene) capsules suggesting the product may delay disease progression in patients with non-small-cell lung cancer, plus Phase II/III open-label trial data showing the Targretin is effective for all stages of cutaneous T-cell lymphoma (CTCL) refractory to prior therapy (the indication for which the product won FDA approval in December 1999). The company also reported preclinical data suggesting that adding arginine butyrate or retinoids to a treatment regimen using the company's Ontak (denileukin difitox; FDA-approved) may boost anticancer activity in patients whose lymphoma cells do not express the interleukin-2 receptor.
¿ Onyx Pharmaceuticals Inc., of Richmond, Calif., reported positive results for CI-1042 (formerly ONYX-015) combined with standard chemotherapy in a variety of tumor types - liver metastases of colorectal cancer via hepatic artery infusion, pancreatic cancer via intratumoral ultrasound injection, ovarian cancer, and refractory cancer containing a p53 mutation. The studies "offer new evidence that the product may prove useful in a wide variety of cancers with mutations within the p53 tumor-suppressor pathway," said Hollings Renton, Onyx's president and CEO. CI-1042 is partnered with Warner-Lambert Co., of Morris Plains, N.J.
¿ Ribozyme Pharmaceuticals Inc., of Boulder, Colo., presented detailed toxicology, pharmacokinetic and safety data on the antiangiogenic drug Angiozyme, a synthetic ribozyme targeting the mRNA of a receptor for vascular endothelial growth factor. In multiple preclinical studies, the drug was shown to halt tumor growth and prevent metastases. In addition, the product was well tolerated in 28-day toxicology studies at doses up to 300 mg/m2 per day. Angiozyme, co-developed with Emeryville, Calif.-based Chiron Corp., is in Phase I/II trials.