Profile: Keryx Biopharmaceuticals Inc (KERX.O)
13 Dec 2013
Keryx Biopharmaceuticals, Inc. (Keryx), incorporated in October 1998, is a biopharmaceutical company focused on the acquisition, development and commercialization of pharmaceutical products for the treatment of cancer and renal disease. The Company is developing KRX-0401 (perifosine), an oral anti-cancer agent that inhibits Akt activation in the phosphoinositide 3-kinase (PI3K) pathway, and also affects a number of other key signal transduction pathways, including the Jun N-terminal kinases (JNK) pathway, all of which are pathways associated with programmed cell death, cell growth, cell differentiation and survival. KRX-0401 is in Phase III clinical development for both refractory advanced colorectal cancer and relapsed / refractory multiple myeloma, and in Phase I and Phase II clinical development for other tumor types. It is also developing Zerenex (ferric citrate), an oral, ferric iron-based compound that has the capacity to bind to phosphate in the gastrointestinal tract and form non-absorbable complexes. Zerenex is in Phase III clinical development in the United States, under a special protocol assessment (SPA), as a treatment for hyperphosphatemia (elevated phosphate levels) in patients with end-stage renal disease (ESRD), on dialysis.
As of December 31, 2011, over 2,000 patients had been treated with KRX-0401 in trials conducted in the United States, Canada, Europe and Israel. In vitro, KRX-0401 inhibits the growth of a range of human tumor cell lines and has demonstrated activity in vivo against a number of murine tumor models and human xenografts. Seven Phase I single agent studies of KRX-0401 have been conducted, including three in Europe by AEterna Zentaris Inc., the licensor of KRX-0401, and four in the United States by the National Cancer Institute (NCI), a department of the National Institutes of Health (NIH), as part of a Cooperative Research and Development Agreement (CRADA), and by the Company. These trials demonstrated that KRX-0401 can be safely given to humans with a manageable toxicity profile. In addition, one Phase I study in the United States is being conducted to evaluate the safety of KRX-0401 in pediatric patients, and another is being conducted to evaluate the effect of KRX-0401 on electrocardiogram parameters, including QTc intervals, as well as the effect of food on KRX-0401 bioavailability.
Fourteen Phase I and Phase II studies of KRX-0401 in combination with other drugs have been conducted by Keryx. Agents that have been included in these combinations include capecitabine (Xeloda), gemcitabine, paclitaxel, docetaxel, prednisone, doxorubicin, pemetrexed, irinotecan, Doxil (doxorubicin HCl liposome injection), trastuzumab, various endocrine therapies, imatinib, bortezomib (Velcade), lenalidomide, sorafenib, and sunitinib. KRX-0401 has generally been well tolerated when used as a low daily dose (50 milligram or 100 milligram) in combination with these approved agents. The NCI has conducted a number of Phase II clinical trials studying KRX-0401 as a single agent, including studies in prostate, breast, head and neck and pancreatic cancers, as well as melanoma and sarcomas. In total, nine NCI clinical trials have been conducted across these six tumor types.
KRX-0401 has also been evaluated in 11 Phase II clinical studies conducted by Keryx evaluating the single agent activity in various tumor types where patients have progressed on standard treatments. In July 2011, the Company announced the completion of patient enrollment. This Phase III trial is being conducted pursuant to an SPA with the FDA and with Fast-Track Designation. On July 27, 2011, it announced the completion of patient enrolment, and on August 31, 2011, it announced that the independent Data Safety Monitoring Board (DSMB), for the Phase III X-PECT trial completed a pre-specified interim analysis for safety and futility. The Phase III trial, entitled the X-PECT (Xeloda + Perifosine Evaluation in Colorectal cancer Treatment) trial, is a randomized (1:1), double-blind trial comparing the efficacy and safety of perifosine + capecitabine vs. placebo + capecitabine in approximately 465 patients with refractory advanced colorectal cancer. As of December 31, 2011, the Company had seven approved drugs for patients with metastatic colorectal cancer: 5-fluorouracil (5-FU), capecitabine (Xeloda), irinotecan (Camptosar), oxaliplatin (Eloxatin), bevacizumab (Avastin), cetuximab (Erbitux), and panitumumab (Vectibix).
Zerenex (Ferric Citrate)
Zerenex (ferric citrate) is an oral, ferric iron-based compound that has the capacity to bind to phosphate in the gastrointestinal tract and form non-absorbable complexes. Zerenex is in an ongoing Phase III program, as a treatment for elevated serum phosphorus levels, or hyperphosphatemia, in patients with ESRD on dialysis, under an SPA agreement with the FDA. Pursuant to the SPA agreement, the Zerenex Phase III registration program in the United States consists of a short-term efficacy study, and a 58-week long-term safety and efficacy study. In April 2011, the Company reported the final dataset from the Phase III short-term efficacy study. Zerenex (ferric citrate) is also in Phase III development in Japan by JT and Torii. On May 2, 2011, it announced positive Scientific Advice from the European Medicines Agency (EMA), for the development of Zerenex for the management and control of serum phosphorus in ESRD patients undergoing dialysis, and in pre-dialysis chronic kidney disease (CKD), patients. On April 28, 2011, it reported the final dataset from the Phase III short-term clinical trial of Zerenex for the treatment of hyperphosphatemia in end-stage renal disease patients on dialysis. The Phase III short-term study was a multicenter, randomized, open-label trial with a two-week washout period, following which patients were randomized 1:1:1 to receive a fixed dose of Zerenex of one gram, six grams or eight grams per day for a treatment period of 28 days.
Keryx Biopharmaceuticals Inc
20th Floor, 750 Lexington Ave.
NEW YORK NY 10022