NEW YORK, Dec. 11 /PRNewswire-FirstCall/ -- Keryx Biopharmaceuticals, Inc. today announced that Dr. Paul Richardson, Clinical Director of the Jerome Lipper Multiple Myeloma Center at the Dana-Farber Cancer Institute (DFCI) in Boston, MA reported positive interim results from the phase II study of KRX-0401 in patients with advanced relapsed and refractory multiple myeloma (MM) at the American Society of Hematology (ASH) 48th Annual Meeting and Exposition in Orlando, FL. KRX-0401, the Company's lead oncology compound under development, is a novel, oral, anticancer agent that modulates Akt and several other important signal transduction pathways, including MAP kinase and JNK. KRX-0401 is currently being evaluated in Phase II clinical trials as a single agent and in combination with other anti-cancer agents across several tumor types. Dr. Richardson, along with Dr. Ken Anderson at DFCI and other leading investigators from MM centers including Emory University, University of Michigan, Alta Bates, City of Hope, University of Virginia and Northwestern University have been instrumental in the pre-clinical and clinical development of perifosine for MM.
The poster (Abstract # 3582), entitled "A Multicenter Phase II Study of Perifosine (KRX-0401) Alone and in Combination with Dexamethasone (Dex) for Patients with Relapsed or Relapsed/Refractory Multiple Myeloma (MM)," was presented today, December 11th, 2006 at 10:30 am in the Orange County Convention Center. In this ongoing Phase II study, patients with relapsed or relapsed/refractory multiple myeloma are treated with KRX-0401 (150 mg oral daily dose) to assess the single agent activity of KRX-0401 in this patient population. If a patient progresses on KRX-0401 alone, dexamethasone (20mg twice weekly) is added to their KRX-0401 regimen.
Results:
55 patients (30 men and 25 women, median age 63 y, range 3879) have been treated to date. All had relapsed and refractory MM, with a median of 4 lines of prior treatment (range 2 - 11). Prior therapy included dex (95%), thalidomide (89%), bortezomib (78%), lenalidomide (31%) and stem cell transplant (73%). Among 33 patients currently evaluable for response, best response (EBMT/Blade criteria) to single agent perifosine after 2 cycles was stable disease (<25% reduction in M-protein) in 13 patients (39%). Dex was added in 30 of 55 patients with PD, with 23 patients evaluable for response on the combination, reported as follows:
Perifosine + Dex N (%) Duration (wks) PR 2 (9%) 13+, 17+ MR 4 (17%) 4, 16+, 28+, 30+ Stable Disease 11 (48%) 6 - 20+ (median 18)* *4 pts ongoing at 16, 18, 20 and 20 weeks
The most common grade 3/4 adverse events were nausea (7%); vomiting (4%); diarrhea (2%); fatigue (2%), and increased creatinine (8% in the context of PD and light chain nephropathy). Dose reduction (150 to 100 or 50 mg/d) was required in 16 patients and 7 patients discontinued treatment due to adverse events. Attributable toxicities otherwise proved manageable with appropriate supportive care. Perifosine was generally well tolerated, with no peripheral neuropathy or DVT seen.
The conclusion of the investigators is that Perifosine alone or in combination with dexamethasone has activity in patients with advanced, relapsed/refractory MM, achieving response and/or stabilization of disease in 69% of evaluable patients to date.
Commenting on the interim data, Dr. Richardson stated, "We are encouraged by the observed activity of perifosine in combination with dexamethasone in relapsed and refractory patients with multiple myeloma, and the manageable toxicity profile seen to date, with some of our patients remaining on active treatment over 6 months. We look forward to completing enrollment in this study while moving forward with clinical trials evaluating perifosine in combination with other novel agents, including bortezomib."
Craig Henderson, MD, President of Keryx Biopharmaceuticals, commented, "We are excited with the KRX-0401 interim phase II clinical results in multiple myeloma. We are grateful to see top institutions in the field coming together led by Dr. Paul Richardson, to conduct this important clinical program for KRX-0401."
KRX-0401 (perifosine) is in-licensed by Keryx from Aeterna Zentaris, Inc. , in the United States, Canada and Mexico.
About KRX-0401 (Perifosine)
KRX-0401 is a novel, first-in-class, oral anticancer agent that modulates AKT and a number of other key signal transduction pathways, including the MAPK and JNK pathways.
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 soft-tissue sarcoma, gastric, hepatocellular, endometrial, prostate, renal cell, head and neck cancers and hematological malignancies, 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) and 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. Perifosine has shown single agent partial responses or long term disease stabilizations in solid tumors including, renal, hepatocellular, sarcoma and prostate cancer. Responding patients, including stable disease, have been treated for months to almost 3 years, on both the daily and weekly schedule.
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) (sulodexide), a first-in-class, oral heparinoid compound for the treatment of diabetic nephropathy, a life- threatening kidney disease caused by diabetes. KRX-101 is in a pivotal Phase 3 and Phase 4 clinical program under a Special Protocol Assessment with the Food & Drug Administration. Additionally, Keryx is 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 2 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 the financial performance and clinical and business prospects for KRX-0401, 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 the Phase 2 clinical trials for KRX-0401; 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 Commissions. 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: Ron Renaud CFO Keryx Biopharmaceuticals, Inc. Tel: 212.531.5965 E-mail: rrenaud@keryx.com
Keryx Biopharmaceuticals, Inc.CONTACT: Ron Renaud, CFO, Keryx Biopharmaceuticals, Inc., +1-212-531-5965,rrenaud@keryx.com
Web site: http://www.keryx.com/
