Results suggest new hope for patients with refractory chronic lymphocytic leukemia Data to support BLA submission
BARCELONA, SPAIN, June 12 ---ILEXTM Oncology, Inc. (NASDAQ: ILXO) and LeukoSite, Inc. (NASDAQ: LKST) today announced final results from an international, multi-center, pivotal Phase II clinical trial of CAMPATHR for the treatment of patients with B-cell chronic lymphocytic leukemia (CLL) who are refractory to fludarabine. Results of the trial were presented this weekend at the 4th Congress of the European Haematology Association (EHA) by Michael J. Keating, MB, BS, of the M.D. Anderson Cancer Center, one of the trial's principal investigators and an internationally recognized expert in CLL. The companies plan to submit a Biologics License Application (BLA) based largely on these results later this year.
"The results of this trial are encouraging," said Dr. Keating, Associate Head for Clinical Research and Professor of Medicine and internist for the Department of Leukemia at M.D. Anderson Cancer Center. "The data suggest that CAMPATH may provide an important new treatment option for fludarabine-refractory patients, a group for whom the prognosis has, to date, been extremely poor. While the treatment of patients with leukemia has relied on chemotherapeutic agents, the use of monoclonal antibodies is an innovative approach to circumventing the disease's mechanisms for resistance."
The non-comparative trial, involved 93 previously treated patients who had received prior alkylating agents and failed fludarabine therapy (median of three prior treatment regimens). For these patients, the median life expectancy is usually six to nine months.
In the trial, patients participating at the 20 clinical sites in the United States and Europe received 30 mg of CAMPATH on an outpatient basis, as an intravenous infusion, three times a week, for four to 12 weeks. The dose was gradually escalated over the first week to 30 mg, in order to reduce the incidence and severity of infusion-related adverse events. Patients also received prophylactic anti-infective treatment to reduce the risk of opportunistic infections. The primary endpoint for this trial was overall response rate (complete and partial response), and the study objective was to demonstrate a major response rate of at least 20 percent. Response rate was assessed by an independent review panel in accordance with the National Cancer Institute's guidelines for the diagnosis and treatment of CLL.
Of 93 evaluable patients, 31 demonstrated an objective response to treatment, for an overall response rate of 33%. Two of these responses were complete (2%) and 29 were partial responses (31%). Another 55 (59%) patients had disease stabilization. Median survival time has not yet been reached at about 10 months after the last patient was enrolled.
The safety profile of CAMPATH was consistent with that seen in previous studies and was judged by the investigators to be acceptable in this group of endstage CLL patients.
Adverse effects associated with CAMPATH in this study of 93 patients were mostly mild to moderate infusion-related symptoms. Severe (grade 3 and 4) infusion-related symptoms included: fever (13%), rigors (11%), dyspnea (6%), and hypotension (1%). During the study patients developed severe (grade 3 and 4) thrombocytopenia (low platelet count, 51%) or neutropenia (low white blood cell count, 61%) that usually improved within two months post-therapy. Some patients entering the study with severe (grade 3 and 4) thrombocytopenia and neutropenia improved to grade 2 or better within two months post-therapy: thrombocytopenia -- 7 of 19 (37%) patients improved,neutropenia -- 11 of 17 (65%) patients improved.
No unexpected serious adverse events were reported. The incidence of serious infections was reported to be 20% on this trial. It should be noted that infection is a common complication and cause of death in this patient population. Six patients (6%) expired from serious adverse events considered to be treatment related. Although not observed in the pivotal trial, rare instances of vascular leak syndrome associated with cytokine release/infusion, marrow aplasia, and tumor lysis syndrome have occurred in earlier non-L&I sponsored studies with a higher cumulative dose and/or different initial schedule.
"As clinicians, we are very pleased with these results. They predict a much brighter future for this patient population," said Dr. Keating. "While none of our therapies are curative, it appears that CAMPATH may be of significant benefit in this patient population. Adding CAMPATH to the armamentarium may very well help us alter the overall natural history of this disease and, with the judicious use of prophylactic agents against infection, minimize the development of serious complications."
CAMPATH, which received "fast track" designation from the FDA, is expected to undergo a six-month priority review by the FDA under the Prescription Drug User Fee Act. Due to its potential to address unmet medical needs for serious or life-threatening conditions, the FDA has made CAMPATH eligible for "rolling" review which means the Biologics License Application (BLA) may be processed as complete sections of the package are submitted.
The FDA has also granted Orphan Drug designation to CAMPATH for CLL.
"The data from this trial confirm our belief in CAMPATH and provide a strong basis for the BLA which we are now preparing in consultation with the FDA," said Christopher Mirabelli, Ph.D., president and chief executive officer of LeukoSite. "CAMPATH is the most advanced in our portfolio of four products in clinical development."
CLL is the most prevalent form of adult leukemia, afflicting approximately 120,000 worldwide. CLL is characterized by an accumulation of malignant lymphocytes (one subclass of white blood cells) in the bone marrow and other tissues, causing bone marrow dysfunction and enlargement of the lymph nodes, liver and spleen. Standard front line therapy consists of alkylating agent based drug regimens. Fludarabine is the only approved drug for the treatment of patients who have failed alkylating agents. No approved therapy is available for patients who fail fludarabine therapy.
CAMPATH appears to work in CLL by depleting malignant CLL cells, which bear the CD52 antigen. CAMPATH is a humanized monoclonal antibody which is directed against the CD52 antigen found on normal and malignant lymphocytes, on normal macrophages and monocytes, but has not been detected on hematopoietic stem cells.
CAMPATH therapy is associated with significant lymphopenia. The lymphopenia resolves in some, but not all, patients over weeks to months after cessation of CAMPATH therapy.
"Early studies suggested the promise of CAMPATH. This study appears to confirm the decision to submit a BLA to the FDA," said Kanti R. Rai, M.D., Chief, Division Hematology-Oncology, Long Island Jewish Medical Center. "CAMPATH may very well become the next new and promising monoclonal antibody therapy for patients with cancer. For our patients with CLL, CAMPATH may change the expectation from one of relentlessly progressive deterioration on palliative therapies to the hope of extended survival," said Dr. Rai, who is also one of the trial's principal investigators and an internationally recognized expert in CLL.
ILEX and LeukoSite are developing CAMPATH through a joint venture that was established in May 1997. Clinical trials in the treatment of non-Hodgkin?s lymphoma, CLL, and other malignancies expressing CD52 are being planned.
"CAMPATH is the most advanced of ILEX's nine compounds and we are anxious to make it available to patients," said Richard L. Love, president and chief executive officer of ILEX.
ILEX Oncology, Inc. is a drug development company focused exclusively on accelerated development of drugs for the treatment and prevention of cancer. The company does this in two ways: by advancing a diversified portfolio of anticancer drugs through its ILEX Products subsidiary, and, by offering drug development services on a contract basis to pharmaceutical and biotech companies through its ILEX Oncology Services subsidiary.
These complementary businesses draw from the company?s core expertise: relationships with international oncology experts, strategic alliances that provide unparalleled access to patient recruitment for clinical trials, and simultaneous European and U.S. drug development and approval capabilities.
Further information about ILEX Oncology, Inc. can be found on the World Wide Web at: www.ilexoncology.com
LeukoSite is a biotechnology company developing proprietary drugs designed to block disease-promoting actions of white blood cells. The focus of LeukoSite's research and development is on drugs for the treatment of cancer and autoimmune and inflammatory diseases. LeukoSite has nine research and development programs underway and four drug candidates in clinical development. The Company is collaborating with Warner-Lambert Co., Roche Bioscience, Kyowa Hakko Kogyo Co., Ltd.,Genentech, Inc. and MorphoSys AG.
News releases issued by LeukoSite, Inc. are available through PR Newswire's "Company News On-Call," by calling 800-758-5804 and entering the Company's extension number 114510.
Certain statements contained herein, such as the companies' intention to file a BLA with the FDA in mid-1999, are "forward-looking" statements (as such term is defined in the Private Securities Litigation Reform Act of 1995).
Because such statements include risks and uncertainties, actual results may differ materially from those expressed or implied by such forward-looking statements. Factors that could cause actual results to differ materially from those expressed or implied by such forward-looking statements include, but are not limited to, risks in technology and product development, failure to successfully complete clinical trials, failure to receive market clearance from regulatory agencies, competitive risks and those risks and uncertainties discussed in filings made by LeukoSite, Inc. and ILEX Oncology, Inc. with the Securities and Exchange Commission. The companies disclaim any obligation to update these forward-looking statements.
Contacts: Augustine Lawlor, LeukoSite, Inc., 617-621-9350 Deborah Sibley, ILEX Oncology, Inc., 210-49-8287