Keryx Biopharmaceuticals, Inc. Announces Phase 1 and Phase 2 Data on KRX-0401 (Perifosine) in Patients with Relapsed/Refractory Multiple Myeloma at 49th Annual Meeting of American Society of HematologyDr. Paul Richardson presents Phase 1 results demonstrating clinical activity of perifosine in combination with bortezomib in patients previously treated with bortezomib, and provides an update on an ongoing Phase 2 study of perifosine in combination with dexamethasone
NEW YORK, December 10, 2007 /PRNewswire-FirstCall/ -- Keryx Biopharmaceuticals, Inc. today announced that positive phase 1 & phase 2 data of perifosine (KRX-0401) in patients with advanced, relapsed/refractory multiple myeloma (MM) were presented on Saturday, December 8, 2007 at the 49th Annual Meeting of the American Society of Hematology. In two separate poster presentations, Dr. Paul Richardson, Clinical Director of the Jerome Lipper Multiple Myeloma Center at the Dana-Farber Cancer Institute (DFCI) in Boston, MA, provided the phase 1 results on the clinical activity of perifosine in combination with Bortezomib, and an update on an ongoing phase 2 study of perifosine in combination with dexamethasone.
Phase 1 Perifosine + VELCADE(R) (Vel)
Poster 324-I: A MULTICENTER PHASE 1/2 TRIAL OF PERIFOSINE (KRX-0401) + BORTEZOMIB IN RELAPSED OR RELAPSED/REFRACTORY MULTIPLE MYELOMA PATIENTS PREVIOUSLY TREATED WITH BORTEZOMIB: PHASE I RESULTS
Eighteen patients (median age 64 yrs) with advanced MM (83% relapsed and refractory) were enrolled in one of four cohorts. Patients had a median of 5 lines of prior therapy and 100% of patients were previously treated with at least one course of therapy on bortezomib. Perifosine was escalated from 50 to 100 mg qd while bortezomib was escalated from 1.0 to 1.3 mg/mm2. No dose- limiting toxicity and no grade 3 peripheral neuropathy were reported. Toxicities were generally well managed and tolerated. Dexamethasone 20mg (day of and day after each Velcade dose) was added in patients with progressive disease (PD) on perifosine plus Velcade alone. Sixteen patients on either Velcade plus perifosine alone or with dexamethasone were evaluable for response, assessed by modified EBMT/Blade criteria, with results as follows:
Relapsed (Rel) or Response (N = 16)* N (%) Relapsed/Refractory MM Duration (wks) CR after Peri + Vel 1 (6%) Rel/Refractory 66+ CR after Peri + Vel + Dex **1 (6%) Rel 36+ PR after Peri + Vel + Dex 1 (6%) Rel/Refractory 33 MR after Peri + Vel 2 (13%) Rel/ Refractory 31+, 19 MR after Peri + Vel + Dex 4 (25%) Rel/Refractory 46, 36+, 19, 13+ SD after Peri + Vel 3 (19%) Rel/Refractory 39+, 39, 26+ SD after Peri + Vel + Dex 2 (13%) 1 pt Rel/Ref; other Rel 38, 19 PD after Peri + Vel 2 (13%) Rel/Refractory 5, 4 Stable disease (SD): < 25% reduction in M-protein **subject to confirmation
*2 pts were inevaluable for response (removed from study after only 1 cycle of treatment) Times with '+' meaning patient still stable or responding at time of analysis.
In summary, the investigators conclude that the combination of perifosine and bortezomib (+/- dexamethasone) was well tolerated and is active in heavily pre-treated and relapsed/refractory multiple myeloma, including bortezomib- resistant patients. An overall response rate of 56% (CR + PR + MR) was reported with an additional 31% of patients achieving stable disease (SD). The phase 2 portion of the study is open with 12 patients enrolled to date with perifosine 50 mg qd + Velcade 1.3 mg/mm2, D1, 4, 8, 11 every 21 days as the selected phase 2 dose.
Phase 2 Perifosine +/- Dexamethasone (dex)
Poster 318-I: MULTI-CENTER PHASE 2 STUDY OF PERIFOSINE (KRX-0401) ALONE AND IN COMBINATION WITH DEXAMETHASONE (DEX) FOR PATIENTS WITH RELAPSED OR RELAPSED/REFRACTORY MM: PROMISING ACTIVITY AS COMBINATION THERAPY WITH MANAGEABLE TOXICITY
Sixty-seven highly pre-treated MM patients (median age 62 yrs) were treated with perifosine at 150 mg qd to assess the single agent activity in this patient population. Patients had a median of 4 lines of prior therapy (range 1 - 11) and 94% of patients were previously treated with at least one course of dex. If a patient progressed on perifosine alone, dex (20mg twice weekly) was added to their perifosine regimen. Toxicity was manageable with no DVT or peripheral neuropathy reported. Twenty-one patients had perifosine reduced from 150 to 100 mg qd with no difference in response noted. In this heavily pre-treated and relapsed/refractory patient population, perifosine as monotherapy appears to have modest activity with 33 of 50 evaluable patients (66%) achieving SD. Dex was added in 39 of 55 pts with progressive disease. Out of 29 patients currently evaluable for response on the combination. an ORR (CR+PR+MR) of 35% (10/29) was achieved, with an additional 52% (15/29) of patients achieving SD. Six patients remain on treatment with duration of response ranging from 15 - 70 weeks. Enrollment objectives were met and the study is now closed.
One additional clinical poster was presented as follows:
Phase 1 Perifosine + REVLIMID(R) + dexamethasone (dex)
Poster 323-I: A MULTIPLE MYELOMA RESEARCH CONSORTIUM (MMRC) MULTICENTER PHASE I TRIAL OF PERIFOSINE (KRX-0401) IN COMBINATION WITH LENALIDOMIDE AND DEXAMETHASONE IN PATIENTS WITH RELAPSED OR REFRACTORY MULTIPLE MYELOMA (MM): UPDATED RESULTS
"The data presented further demonstrates perifosine's promising activity in combination with bortezomib, lenolidomide and dexamethasone," stated Dr. Richardson, who continued, "we are especially encouraged by the activity of perifosine combinations in resistant patients and the favorable toxicity profile seen to date. We look forward to completing enrollment in both the perifosine/bortezomib and the perifosine/ lenalidomide/dexamethasone studies in the near future."
I. Craig Henderson, MD, President of Keryx Biopharmaceuticals, commented "The collaboration between Keryx and groups of multiple myeloma physicians, often lead by the group from the Dana-Farber Cancer Institute, and with the involvement of the Multiple Myeloma Research Consortium (MMRC) has been very rewarding. Together these studies provide considerable evidence that perifosine has activity in this disease and suggests possible directions for future development of the drug."
Copies of the posters are available by request to Keryx Biopharmaceuticals.
Perifosine (KRX-0401) Mechanism of Action and Profile
Perifosine 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 perifosine 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 1,500 patients have been treated with perifosine in trials conducted both in the US and Europe. Its safety profile is believed to be distinctly different from that of most cytotoxic agents. It does not appear to cause myelosuppression (depression of the immune system) or alopecia (hair loss) like many currently available treatments for cancer. In phase 1/2 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.
KRX-0401 (perifosine) is in-licensed by Keryx from Aeterna Zentaris, Inc. in the United States, Canada and Mexico.
About Keryx Biopharmaceuticals, Inc.
Keryx Biopharmaceuticals, Inc. is focused on the acquisition, development and commercialization of medically important, novel pharmaceutical products for the treatment of life-threatening diseases, including diabetes and cancer. Keryx's lead compound under development is Sulonex(TM) (sulodexide oral gelcap), 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 3 and Phase 4 clinical program under a Special Protocol Assessment with the Food & Drug Administration. Additionally, Keryx is developing Zerenex(TM), an oral, iron- based compound that has the capacity to bind phosphate and form non-absorbable complexes. Zerenex is currently in Phase 2 clinical development for the treatment of hyperphosphatemia (elevated serum phosphorous 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 anti-cancer agent that modulates Akt, a protein in the body associated with tumor survival and growth, and a number of other key signal transduction pathways, including the JNK and MAPK pathways, which are pathways associated with programmed cell death, cell growth, cell differentiation and cell survival. 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.
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 1 and 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 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: Lauren Fischer Director - Investor Relations Keryx Biopharmaceuticals, Inc. Tel: 212.531.5965 E-mail:email@example.com
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Posted: December 2007