SEATTLE, Oct. 23 /PRNewswire-FirstCall/ -- ZymoGenetics, Inc. today presented positive Phase 1 interim data from a Phase 1/2 trial of Interleukin 21 (IL-21) in combination with Nexavar(R) (sorafenib) in patients with renal cell cancer. Preliminary data from the Phase 1 trial suggests that the combination of IL-21 and sorafenib is well tolerated, with a toxicity profile similar to known toxicities of each agent alone. This combination therapy has also shown promising anti-tumor activity.
"IL-21's unique mechanism of action makes it an ideal potential candidate for combination with approved targeted agents in renal cell cancer," said Nicole Onetto, M.D., Senior Vice President and Chief Medical Officer of ZymoGenetics. "We were very pleased to see that the combination of IL-21 and Nexavar can be safely administered for repeated courses, and that the majority of patients treated to date experience tumor shrinkage. The Phase 2 part of this trial should allow us to confirm these promising results."
Results were presented at the AACR-NCI-EORTC International Conference on "Molecular Targets and Cancer Therapeutics" held in San Francisco. ZymoGenetics is in the process of finishing the Phase 1 part of the study evaluating the combination therapy in patients with clear cell histology, which accounts for 85% of all renal cell tumors. The Phase 2 portion of the study is expected to begin before year end and will examine a larger patient group treated with the maximum tolerated dose of IL-21.
To date, a total of 13 evaluable patients have been enrolled in the Phase 1 portion of the study and treated at one of three dose levels (10, 30 and 50 mcg/kg of IL-21). Treatment consists of IL-21 administered IV on days 1-5 and 15-19 of a 6 week treatment course in combination with sorafenib administered at the recommended dose of 400 mg twice a day. Patients with Stable Disease or better per RECIST are eligible to receive repeat treatment.
Overall, the majority of adverse events and lab abnormalities have been mild to moderate and consistent with the known safety profiles of IL-21 and sorafenib. Dose limiting toxicities consisting of skin-related events have occurred in a total of two patients, including one in the 10 mcg/kg cohort (hand-foot syndrome), and one in the 50 mcg/kg cohort (rash).
11 patients have completed at least one 6-week treatment course, all of whom have gone on to receive repeat treatment, which has not been associated with increased toxicity. 10 of these 11 patients have had measurable disease per RECIST criteria, and all 10 have had a decrease in tumor mass as their best response on study, ranging from 18 to 33% per investigator assessment. Four patients had unconfirmed Partial Responses, with at least 30% decrease in tumor measurements per investigator assessment and 3 of these are still on treatment. Of the 11 patients who finished the first treatment course, nine continue to receive therapy on study, and two patients discontinued therapy due to disease progression.
Renal Cell Cancer
There will be an estimated 51,190 new cases of renal cell carcinoma in the U.S. in 2007. It is estimated that renal cell carcinoma will result in approximately 19,600 deaths in the U.S. in 2007. Renal cell carcinoma accounts for approximately 2% of cancers worldwide. There is a clear need for new and improved therapies for renal cell cancer.
IL-21 in Combination with Tyrosine Kinase Inhibitors
Because tyrosine kinase inhibitors (TKIs) such as Nexavar and Sutent(R) inhibit the growth of tumor cells, and IL-21 activates the immune system to target killing of tumor cells, the two therapies may provide additive or synergistic effects. Treatment with a TKI may make cancer cells more sensitive to natural killer or T cell mediated killing after activation with IL-21. Preclinical research conducted by ZymoGenetics of TKIs and IL-21 found that IL-21 had additive anti-tumor effects when combined with a TKI in a renal cell cancer model.
Previous IL-21 studies
Previous clinical studies with IL-21 have shown that IL-21 is an active cytokine that can be administered in an outpatient regimen. Results from a Phase 1 study presented at the American Society of Clinical Oncology (ASCO) 2006 annual meeting showed that IL-21 administration was well tolerated in an outpatient setting, and that reductions in tumor size, including clinical responses per RECIST criteria, were observed in several patients. Available clinical data support further clinical investigation of IL-21 as a new therapeutic agent for the treatment of cancer.
About IL-21
IL-21 has potent biological activity in regulating key classes of immune cells, including cytotoxic T cells and natural killer cells. These cell types play important roles in eliminating malignant and infected cells. Based upon the ability of IL-21 to inhibit tumor growth in a number of animal models, ZymoGenetics is developing IL-21 for the treatment of cancer, initially in metastatic melanoma and renal cell carcinoma, and has retained commercialization rights for IL-21 in North America. The company licensed commercialization rights outside of North America to Novo Nordisk A/S.
About ZymoGenetics
ZymoGenetics creates novel protein drugs with the potential to significantly help patients fight their diseases. The company is developing a diverse pipeline of product candidates that are moving into and through clinical development. These candidates span a wide array of clinical opportunities that include bleeding, autoimmune and viral diseases and cancer. ZymoGenetics intends to commercialize these product candidates through internal development, collaborations with partners, and out-licensing of patents from its extensive patent portfolio. For further information, visit http://www.zymogenetics.com.
This press release contains "forward-looking statements" within the meaning of the Private Securities Litigation Reform Act of 1995. These forward-looking statements are based on the current intent and expectations of the management of ZymoGenetics. These statements are not guarantees of future performance and involve risks and uncertainties that are difficult to predict. ZymoGenetics' actual results and the timing and outcome of events may differ materially from those expressed in or implied by the forward-looking statements because of risks associated with our unproven discovery strategy, preclinical and clinical development, regulatory oversight, intellectual property claims and litigation and other risks detailed in the company's public filings with the Securities and Exchange Commission, including the company's Annual Report on Form 10-K for the year ended December 31, 2006. Except as required by law, ZymoGenetics undertakes no obligation to update any forward-looking or other statements in this press release, whether as a result of new information, future events or otherwise.
CONTACT: Investor and Media Relations, Susan W. Specht, MBA, Associate
Director, Corporate Communications of ZymoGenetics, Inc., +1-206-442-6592
Web site: http://www.zymogenetics.com/
