NEW YORK, June 3 /PRNewswire-FirstCall/ -- Keryx Biopharmaceuticals, Inc. today announced positive data of KRX-0401 (perifosine) in patients with advanced renal cell carcinoma (RCC). These patients were a cohort of a phase II, multi-center trial of KRX-0401 that included multiple tumor types. All patients in this study were to have had prior standard therapy. Although the extent of prior treatment varied with tumor type, most patients had received two chemotherapy regimens for metastatic disease. An interim analysis was performed at the end of the first year of accrual, and the results in the renal group met protocol requirements for expansion of this cohort. The study is ongoing.
Thirteen patients with advanced renal cell carcinoma (RCC) were enrolled in the study and 7 were evaluable for response. Three of these (43%) had a partial response and an additional 2 patients (29%) achieved long-term stable disease. Two progressed. Four patients were inevaluable because they stopped treatment early (42-62 days) and their disease was not evaluated at the time drug was stopped. Two patients have not been on study long enough to reach the first point of evaluation. Responses were scored using RECIST criteria.
Response N (%) Duration (months)
Partial Response 3 (43%) 4, 4+, 9
Stable Disease 2 (29%) 8+, 11
Progression 2 (29%) 2, 3
Too Early 2
Not Evaluable 4
Times with '+' meaning patient still stable or responding at time of analysis.
Additional renal patients will be enrolled on this study, including patients with prior exposure to sorafenib and sunitinib. Keryx anticipates that phase I studies combining KRX-0401 with approved agents for the treatment of renal cell cancer will be opened within 6-8 weeks. Larger and more definitive phase II and phase III trials are being developed, and it is anticipated that one or more of these will be initiated in the next 6 - 12 months.
"The Akt pathway is frequently activated in renal cell cancers. It follows that this tumor type may be particularly responsive to Akt inhibition, and we think these studies with KRX-0401 may be providing early evidence of this," said I. Craig Henderson, M.D., President of Keryx Biopharmaceuticals. Henderson also added, "Therapy with KRX-0401 could potentially provide an important advancement in the treatment of renal cell carcinoma (RCC), a disease that affects 39,000 new patients every year in the US."
"Recent approvals of sorafenib and sunitinib provide great hope for patients with renal cell carcinoma. However, additional treatments are desperately needed, particularly agents with a different mechanism of action," stated Robert Figlin, MD, professor of medicine and urology, David Geffen School of Medicine at UCLA. "This response data is preliminary but of great interest and we are anxious to further explore the potential of perifosine, a novel agent that targets Akt and other important pathways known to cause resistance in renal cell carcinoma (RCC)."
About the Phase II Trial Design
This company-sponsored, exploratory trial was designed to evaluate the safety and efficacy of two schedules of KRX-0401 (perifosine) in patients with a variety of tumor types. From February 2005 to February 2006, patients at over 30 centers across the US were randomized to receive either 50 mg of perifosine once daily or 1200 mg on a weekly dose schedule. The protocol was designed to accrue 11 patients in a given tumor type and then expand that cohort to 26 patients if a favorable outcome is seen in at least 1 of the first 11 patients. The study continues to enroll patients, and no cohort defined by tumor type has been closed because of insufficient evidence of activity. The responses we have seen in this advanced renal cell carcinoma cohort did not appear dose-dependent as partial responses and stable disease were noted in both dose groups. This is consistent with prior data with KRX- 0401 where responses have been equally distributed between higher and lower dose groups.
Toxicity
The 50 mg dose has been extremely well tolerated. The main toxicities were nausea, vomiting, diarrhea, and fatigue. Nearly half (42%) of the patients on this dose had none of these symptoms, and 89% had no gastrointestinal toxicity above grade 1. The incidence of grade 2 or greater toxicity with the weekly dose was considerably higher, but even in this group nearly 20% experienced none of these side effects and one third no gastrointestinal toxicity above grade 1. The frequency of grade 2 or higher toxicity by study arm was:
Adverse Event 50 mg Daily Arm 1200 mg Weekly Arm
N = 90 N = 95
Nausea 5 (6%) 30 (32%)
Vomiting 4 (5%) 19 (20%)
Diarrhea 5 (6%) 34 (36%)
Fatigue 13 (14%) 27 (28%)
KRX-0401 (perifosine) Mechanism of Action and Profile
KRX-0401 has been shown to inhibit or otherwise modify signaling through a number of different signal transduction pathways including Akt, MAPK, and JNK. Akt isoforms have been found to be overexpressed in renal, breast, prostate, and pancreatic cancers. Elevated levels of pAkt have been correlated with poor prognosis in patients with gastric, hepatocellular, endometrial, prostate, renal cell and head and neck cancers, as well as glioblastoma. The majority of tumors expressing high levels of pAkt were high-grade, advanced stage or had other features associated with poor prognosis.
The effects of KRX-0401 on Akt are of particular interest because of 1) the importance of this pathway in the development of most cancers; 2) the evidence that it is often activated in tumors that are resistant to other forms of anticancer therapy; and 3) the difficulty encountered thus far in the discovery of drugs that will inhibit this pathway without causing excessive toxicity.
To date, over 900 patients have been treated with KRX-0401 in trials conducted both in the US and Europe. Its safety profile is distinctly different from that of most cytotoxic agents. It does not cause myelosuppression (depression of the immune system) or alopecia (hair loss) like many currently available treatments for cancer. In phase I/II trials it has induced tumor regressions and/or caused disease stabilization in a variety of tumor types. Responding patients, including stable disease, have been treated for months to almost 3 years, on both the daily and weekly schedule.
About Renal Cell Carcinoma
RCC represents approximately 2% to 3% of all adult cancers worldwide and 2% of all cancer-related deaths. In 2006, an estimated 39,000 new cases of RCC and 13,000 deaths attributable to RCC are expected in the US. The National Cancer Institute reports a rising incidence of RCC at a rate of approximately 2% per decade. The disease occurs predominantly in the seventh and eighth decades in life, and it affects nearly twice as many men as women.
About Keryx Biopharmaceuticals, Inc.
Keryx Biopharmaceuticals, Inc. is focused on the acquisition, development and commercialization of novel pharmaceutical products for the treatment of life-threatening diseases, including diabetes and cancer. Keryx's lead compound under development is Sulonex(TM), previously referred to as KRX-101, a first-in-class, oral heparinoid compound for the treatment of diabetic nephropathy, a life-threatening kidney disease caused by diabetes. Sulonex is in a pivotal Phase III and Phase IV clinical program under a Special Protocol Assessment with the Food & Drug Administration. Additionally, Keryx is developing Zerenex(TM), an oral, inorganic, iron-based compound that has the capacity to bind to phosphorous and form non-absorbable complexes. Zerenex is currently in Phase II clinical development for the treatment of hyperphosphatemia (elevated phosphate levels) in patients with end-stage renal disease. Keryx is also developing clinical-stage oncology compounds, including KRX-0401, a novel, first-in-class, oral modulator of Akt, a pathway associated with tumor survival and growth, and other important signal transduction pathways. KRX-0401 is currently in Phase II clinical development for multiple tumor types. Keryx also has an active in-licensing and acquisition program designed to identify and acquire additional drug candidates. Keryx is headquartered in New York City.
Cautionary Statement
Some of the statements included in this press release, particularly those anticipating future clinical results and future clinical trials for KRX-0401 and similar matters, may be forward-looking statements that involve a number of risks and uncertainties. For those statements, we claim the protection of the safe harbor for forward-looking statements contained in the Private Securities Litigation Reform Act of 1995. Among the factors that could cause our actual results to differ materially are the following: our ability to successfully complete cost-effective clinical trials for KRX-0401; the risk that the data (both safety and efficacy) from the Phase II study referenced in this press release when complete will not coincide with the interim data analysis discussed in this press release; we may not be able to meet anticipated development timelines for KRX-0401 due to recruitment, clinical trial results, manufacturing capabilities or other factors; and other risk factors identified from time to time in our reports filed with the Securities and Exchange Commission. Any forward-looking statements set forth in this press release speak only as of the date of this press release. We do not intend to update any of these forward-looking statements to reflect events or circumstances that occur after the date hereof. This press release and prior releases are available at http://www.keryx.com/. The information in our website is not incorporated by reference into this press release and is included as an inactive textual reference only.
KERYX CONTACT:
Ronald C. Renaud, Jr.
Chief Financial Officer
Keryx Biopharmaceuticals, Inc.
Tel: 212.531.5965
E-mail:
