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Phase II Trial of Repifermin Demonstrate Safety and Efficacy in Patients With Cancer Therapy-induced Mucositis

ROCKVILLE, Md., April 2 /PRNewswire-FirstCall/ -- Human Genome Sciences, Inc. (NASDAQ:HGSI) announced today that results from a Phase 2 clinical trial demonstrate that repifermin (keratinocyte growth factor-2, KGF-2) is well- tolerated and shows efficacy in treating cancer therapy-induced mucositis. Repifermin is a novel human protein discovered by Human Genome Sciences that stimulates the repair of injured skin and mucosal tissues.

The double-blind, placebo-controlled, dose-escalation Phase 2 clinical study was designed to determine repifermin's safety and tolerability, optimal dosing schedule, and preliminary efficacy.(1) The study was conducted at multiple centers in patients who underwent chemotherapeutic conditioning regimens for autologous hematopoietic stem cell transplantation. Forty-two patients were enrolled in the study. Repifermin was administered intravenously both prior to the conditioning regimen and following the autologous hematopoietic stem cell transplantation. Patients were administered placebo or 25 mcg/kg or 50 mcg/kg of repifermin daily for three days prior to the conditioning regimen, and daily for ten days following transplantation. Safety was the primary endpoint of the study protocol. Secondary endpoints included incidence, severity, and duration of mucositis.

The results show that repifermin is well tolerated with no differences from placebo in adverse events or laboratory abnormalities. Repifermin significantly reduced the incidence of grade two to grade four mucositis compared to control patients (p The current study was conducted under an amended protocol to a Phase 2A study completed and reported in December 2001.(1, 2) Under the original protocol, ninety-one patients underwent high-dose chemotherapeutic conditioning regimens, with or without total body irradiation, for autologous hematopoietic stem cell transplantation, followed by fourteen days of daily repifermin administration. Safety was the primary endpoint of the study. Results of the original dose-escalation Phase 2A study showed that repifermin was well tolerated with no differences from placebo in adverse events or laboratory abnormalities. The original study, which evaluated repifermin in a dosing regimen that is no longer believed to be optimal, showed no evidence that repifermin was active in reducing the incidence or severity of mucositis. The amended protocol for the current study built upon emerging preclinical data and called for the administration of repifermin both prior to the conditioning regimen and following the autologous hemato poietic stem cell transplantation. The protocol for the original study did not include repifermin dosing prior to the conditioning regimen.

Cesar O. Freytes, M.D., F.A.C.P., Director, Adult Bone Marrow Transplant Program, University of Texas Medical Center at San Antonio and South Texas Veterans Health Care System, said, "We were encouraged by the results, which showed that repifermin was well tolerated and significantly reduced the incidence of mucositis in patients undergoing chemotherapeutic conditioning regimens prior to autologous hematopoietic stem cell transplantation. These results support the decision to administer repifermin on a schedule both prior to and following the conditioning regimen. We believe that continued evaluation of repifermin is warranted and that repifermin may have the potential to offer a new approach to treating mucositis."

David C. Stump, M.D., Senior Vice President, Drug Development, Human Genome Sciences, said, "These Phase 2 clinical results demonstrate that repifermin shows efficacy and provide additional evidence of repifermin's excellent safety profile. Importantly, the current trial evaluated the administration of repifermin in a dosing regimen that we believe is much more appropriate in this treatment setting. The addition of dosing prior to the chemotherapeutic conditioning regimen is supported strongly by a number of preclinical studies.(3) The current data are consistent with that preclinical evidence. We plan to meet with the FDA, our clinical investigators, and our partner, GlaxoSmithKline, to determine the best path forward for confirming the efficacy and safety of repifermin for this clinical indication. Mucositis is a significant dose-limiting side effect of cancer therapy. We continue to believe that repifermin can play a significant role in treating the patients who suffer from it."

Mucositis occurs when radiation or chemotherapy, given to destroy rapidly dividing cancer cells, also destroys other rapidly proliferating cells such as those lining the mouth and gastrointestinal tract. Mucositis is an inflammation of the mucous membrane and occurs in the oral cavity and throughout the gastrointestinal tract. Its symptoms include ulcerations, redness and swelling. In severe cases, mucositis can be so debilitating that patients may require prolonged hospitalization in order to receive sufficient nutrition and narcotic pain medication. The destruction of the protective mucous membrane also may lead to serious infection, placing the patient at risk for sepsis and death. Human Genome Sciences also is developing repifermin as a potential treatment for chronic venous ulcers.(4,5) In 2000, GlaxoSmithKline exercised an option to develop and market repifermin jointly with Human Genome Sciences, starting with Phase 3 trials. For more information on repifermin, see www.hgsi.com/products/kgf2.html. For additional information on Human Genome Sciences, please visit our web site at www.hgsi.com. Health professionals or patients interested in inquiring about repifermin trials or any other study involving HGSI products are encouraged to inquire via the Contact Us section of the Human Genome Sciences web site, www.hgsi.com/products/request.html, or by calling (301) 610-5790, extension 3550.

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