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Keryx Biopharmaceuticals Announces Positive Data from a Randomized, Multi-Center, Placebo-Controlled, Phase 2 Combination Study of KRX-0401 (Perifosine) in the Treatment of Advanced Metastatic Colon Cancer

Posted on: Monday, 1 June 2009, 07:30 CDT

KRX-0401 + Capecitabine More Than Doubles Time to Progression and Overall Response Rate as well as Extends Overall Survival vs. Capecitabine + Placebo in Patients with 2nd or 3rd Line Metastatic Colon Cancer

NEW YORK, June 1 /PRNewswire-FirstCall/ -- Keryx Biopharmaceuticals, Inc. (Nasdaq: KERX) yesterday announced data on the clinical activity of KRX-0401 (perifosine), the Company's Akt-inhibitor for cancer, in combination with capecitabine as a treatment for advanced colon cancer. Abstract #4081, entitled, "Randomized phase II study of perifosine in combination with capecitabine versus capecitabine alone in patients with second- or third-line metastatic colon cancer," was presented yesterday in a poster during the Gastrointestinal Cancer -- Colorectal session at the 45th Annual Meeting of the American Society of Clinical Oncology (ASCO), taking place in Orlando, Florida.

In this randomized, double-blind, placebo-controlled study conducted at 11 centers across the United States, patients with 2nd or 3rd line metastatic colon cancer were randomized to receive capecitabine (Xeloda(R)), an approved drug for metastatic colon cancer, at a dose of 825 mg/m2 BID (total daily dose of 1650 mg/m2) on days 1-14 every 21 days, plus either perifosine or placebo at 50 mg daily. Treatment was continued until progression. The study enrolled a total of 38 patients, of which 35 patients were evaluable for response (20 patients on the capecitabine + perifosine arm and 15 patients on the capecitabine + placebo arm). The three patients not evaluable for response were all in the capecitabine + placebo arm; 2 patients were inevaluable due to toxicity (days 14, 46) and 1 patient was inevaluable due to a new malignancy on day 6.

The median prior treatment regimens was two, with prior treatment regimens as follows: 91% of the patients received prior FOLFIRI (Irinotecan + 5FU + Leucovorin); 74% prior FOLFOX (Oxaliplatin + 5FU + Leucovorin); 63% were previously treated with both FOLFIRI and FOLFOX; 77% received prior Avastin(R); and 43% prior Erbitux(R). Prior treatment with single agent capecitabine was excluded.

The primary endpoints of this study were to measure 1) Time to Progression (TTP); 2) Overall Response Rate (ORR), defined as the percentage of patients achieving a Complete Response (CR) or Partial Response (PR) by RECIST, and 3) Clinical Benefit Rate (CBR) defined as the percentage of patients on treatment for greater than three months with at least stable disease. Safety of perifosine + capecitabine vs. capecitabine + placebo in this patient population was evaluated as a secondary endpoint. Perifosine in combination with capecitabine was well tolerated with hand/foot syndrome (14%) and anemia (11%) as the highest reported grade 3/4 adverse events.

Best response and median time to progression of capecitabine + perifosine vs. capecitabine + placebo were as follows:

Group SD > 12 N CR PR ORR Wks CBR Median TTP N(%) N(%) N(%) N(%) N(%) (wks) Capecitabine 20 1 3 4 11 15 28.9 weeks + Perifosine (5%) (15%) (20%) (55%) (75%) {95% CI (13, 48.1)} Capecitabine + Placebo 15 0 1 1 5 6 11 weeks (7%) (7%) (33%) (40%) {95% CI (9, 15.9)}

Perifosine + capecitabine more than doubled time to progression vs. capecitabine + placebo with a statistically significant p-value = 0.0006. In addition, perifosine + capecitabine more than doubled the ORR and almost doubled the Clinical Benefit Rate vs. capecitabine + placebo.

Although not a primary endpoint in the study, overall survival was analyzed with results as follows:

Group Median Overall Survival* % change (months) Capecitabine + Perifosine 22 {95% CI (12.1, NR)} 26% Increase** Capecitabine + Placebo 16.3 {95% CI (5.3, 17.1)} * Survival calculated from date of randomization until date of death from any cause, whether or not additional therapies were received after removal from treatment ** As of May 2009, median overall survival in the perifosine + capecitabine patient group is ongoing with 10 of the 20 patients in this arm still alive.

Dr. Howard Burris, Chief Medical Officer and Director of Drug Development for the Sarah Cannon Research Institute, Nashville TN, an investigator involved in the Keryx-sponsored perifosine clinical program since 2004, remarked, "The results demonstrate that the addition of perifosine to capecitabine more than doubled time to progression and response rates, along with extending survival vs. capecitabine alone. Although not a large sample size, the data here is very interesting and next steps should be considered."

Ron Bentsur, Chief Executive Officer of Keryx, commented, "Patients with advanced metastatic colon cancer, who fail standard first and second line treatment, are truly in need of additional therapies. We are excited about the data as the combination of perifosine and capecitabine, two oral agents, appears to demonstrate superior clinical benefit over capecitabine alone in this advanced patient population. We will now explore plans to move this program forward in patients with advanced colorectal cancer." Mr. Bentsur added, "We wish to thank all the study investigators for their dedication to this clinical trial."

A copy of abstract #4081 is currently available and can be viewed on-line through the ASCO website: http://www.asco.org/. A copy of the poster may be obtained by contacting the Company.

KRX-0401 (perifosine) is in-licensed by Keryx from Aeterna Zentaris, Inc. (Nasdaq: AEZS; TSX: AEZ) in the United States, Canada and Mexico.

About Colon Cancer

According to the American Cancer Society, not counting skin cancers, colorectal cancer is the third most common cancer diagnosed in the United States. It is estimated that 106,100 people will be diagnosed with colon cancer, 40,870 people will be diagnosed with rectal cancer and approximately 50,000 deaths will be attributable to some form of colorectal cancer in 2009. Surgery is often the main treatment for early stage colon cancer. When colon cancer metastasizes (spreads to other parts of the body such as the liver) chemotherapy is commonly used. Treatment of patients with recurrent or advanced colon cancer depends on the location of the disease. Chemotherapy regimens (i.e. FOLFOX or FOLFIRI either with or without bevacizumab) have shown to increase survival rates for some stages of colorectal cancer. Currently, there are seven approved drugs for patients with metastatic colorectal cancer: 5-FU, capecitabine (Xeloda(R)), irinotecan (Camptosar(R)), oxaliplatin (Eloxatin(R)), bevacizumab (Avastin(R)), cetuximab (Erbitux(R)), and panitumumab (Vectibix(R)). Depending on the stage of the cancer, two or more of these types of treatment may be combined at the same time or used after one another.

About Keryx Biopharmaceuticals, Inc.

Keryx Biopharmaceuticals is focused on the acquisition, development and commercialization of medically important, novel pharmaceutical products for the treatment of life-threatening diseases, including renal disease and cancer. Keryx is developing Zerenex(TM)(ferric citrate), an oral, iron-based compound that has the capacity to bind to phosphate and form non-absorbable complexes. Zerenex has recently completed a Phase 2 clinical program as a treatment for hyperphosphatemia (elevated phosphate levels) in patients with end-stage renal disease. The Company is also developing KRX-0401 (perifosine), a novel, potentially first-in-class, oral anti-cancer agent that modulates Akt, a protein in the body associated with tumor survival and growth. KRX-0401 also modulates 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. The Company also actively engages in business development activities that include seeking strategic relationships for its product candidates and for the Company, as well as evaluating compounds and companies for in-licensing or acquisition. Keryx is headquartered in New York City.

Cautionary Statement

Some of the statements included in this press release, particularly those anticipating future 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 clinical trials for KRX-0401; our ability 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 www.keryx.com. The information in our website and in the American Society of Clinical Oncology's 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: 212.531.5962 E-mail: lfischer@keryx.com

SOURCE Keryx Biopharmaceuticals, Inc.

Source: PR Newswire

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