FDA approves new treatment, Campath ®, humanized monoclonal antibody, for patients with B-cell chronic lymphocytic leukemia

May 07, 2001

Berlex Laboratories to market a new option for patients with refractory, or hard-to-treat, B-CLL

MONTVILLE, N.J., May 8, 2001 -- The U.S. Food and Drug Administration (FDA) late yesterday cleared Campath® (alemtuzumab) humanized monoclonal antibody for marketing as a treatment for patients with B-cell chronic lymphocytic leukemia (B-CLL) who have been treated with alkylating agents and have failed fludarabine therapy. With this decision, Berlex Laboratories, Inc., the U.S. affiliate of Schering AG, Germany (NYSE: SHR), will provide patients with refractory B-CLL a new treatment option. Campath therapy for B-CLL was developed by M&I Partners, a 50-50 joint venture of Millennium Pharmaceuticals, Inc., (NASDAQ: MLNM) and ILEX Oncology, Inc., (NASDAQ: ILXO). Campath will be marketed and distributed in the United States by Berlex Laboratories, Inc., of Montville, N.J.

"This approval is good news for patients with refractory B-CLL. Campath provides a new option for refractory patients who have no other approved therapeutic options available," said Kanti Rai, M.D., chief of the division of hematology and oncology, Long Island Jewish Medical Center and a principal investigator in the Campath clinical trials.

Chronic lymphocytic leukemia is the most prevalent form of adult leukemia, affecting approximately 120,000 patients in the U.S. and Europe. B-CLL is characterized by an accumulation of leukemic (malignant) lymphocytes that often bear the CD52+ antigen, in the bone marrow, blood, and other tissues. As a result of the accumulation of malignant lymphocytes, bone marrow dysfunction and enlargement of the lymph nodes, liver, and spleen may occur. Patients with B-CLL may suffer from disease-related symptoms such as fatigue, bone pain, night sweats, and decreased appetite and weight loss.

Campath appears to work by targeting the CD52+ antigen on the malignant lymphocytes. Campath binds to CD52+, an antigen that is present on the surface of certain leukemic lymphocytes, and induces antibody-dependent lysis (killing) following binding. This results in the removal of the malignant lymphocytes from the blood, bone marrow, and other affected organs. In responders, treatment with Campath may improve blood counts and decrease the size of the liver and spleen. The CD52+ antigen is also found on nonmalignant (normal) lymphocytes, monocytes, macrophages, NK cells, some granulocytes, and some normal bone marrow cells.

Boxed Warning Summary: Campath should be administered under the supervision of a physician experienced in the use of antineoplastic agents. Hematologic toxicity: Serious and, in rare instances fatal, pancytopenia/marrow hypoplasia, autoimmune idiopathic thrombocytopenia, and autoimmune hemolytic anemia have occurred in patients receiving Campath therapy. Infusion reactions: Campath can result in serious infusion reactions. Infections, opportunistic infections: Serious, sometimes fatal bacterial, viral, fungal, and protozoan infections have been reported in patients receiving Campath.

Summary of Efficacy and Safety Data

In evaluating Campath, the FDA reviewed efficacy data from a single arm, clinical trial (Study 211) involving 93 patients with B-CLL, as well as two earlier supporting trials involving 32 B-CLL patients (Study 005) and 24 B-CLL patients (Study 009), respectively. Seventy percent or more of the patients participating in each of these trials had advanced disease (Rai Stage III/IV). All of the study participants in Study 211 had received previous therapy with alkylating agents and were refractory to fludarabine. In Study 211, an overall response rate of 33% (31 of 93 patients) was observed with a median duration of response of about seven months. Response rates on the two supporting trials were 21% (7 of 32 patients) and 29% (7 of 24 patients) respectively, while the median durations of response were about seven and eleven months, respectively.

In Study 211, a 30 percent mortality rate (28 deaths) was observed on study or within six months after completion of the study. Half of these deaths were determined to be due to the progression of B-CLL and half were due to complications related to Campath therapy. Adverse events associated with Campath therapy include infusion-related events, infections, and hematological toxicity. Common infusion-related toxicities included fever and rigors in over 80% of patients treated with Campath, nausea, vomiting, and rash in 40% of patients, and hypotension in about 32% of patients. Most of these events were mild (National Cancer Institute Common Toxicity Criteria [NCI-CTC] Grade 1 or 2) with serious (NCI-CTC Grade 3 or 4) events in less than 20% of patients. Infusion-related events are usually controlled with premedication and post-therapy medications including acetaminophen, diphenhydramine, corticosteroids, and meperidine.

In the most recent study (Study 211) infections of any severity, including sepsis and pneumonia, were reported in about 44% of the study population. About 75% of these infections were serious (NCI-CTC Grade 3 or 4) in nature and about 20% were fatal. Slightly more than half of these serious (NCI-CTC Grade 3 or 4) infections occurred on study or within thirty days after completion of therapy with the others occurring two to six months after discontinuation of therapy. Opportunistic infections such as CMV, Candidiasis, Aspergillosis, Mucormycosis, Pneumocytiis carinii pneumonia (PCP), Herpetic infections, and Cryptococcus were reported in about 25% of the study population. Use of prophylaxis with trimethoprimsulfa appears to have reduced the incidence of PCP infections on this study. Antiviral prophylaxis with famciclovir was also utilized. It is not known if prophylaxis affected the incidence of viral infections.

Hematological toxicities that were observed in the three studies included anemia in 80% of the study participants with serious (NCI-CTC Grade 3 or 4) anemia in 38 %, neutropenia in 85% with serious (NCI-CTC Grade 3 or 4) neutropenia in 64%, and thrombocytopenia in 72% with serious (NCI-CTC Grade 3 or 4) thrombocytopenia in 50%. Other serious hematological toxicities include serious and sometimes fatal bone marrow hypoplasia, autoimmune hemolytic anemia, and autoimmune thrombocytopenia related to Campath therapy. In most instances, hematological toxicity resolved within two months of discontinuation of Campath therapy, however in others, complete recovery was not documented with follow-ups of more than one year.

"Berlex is extremely pleased to offer patients with refractory B-CLL a new treatment option," said Dale A. Stringfellow, Ph.D., president and CEO of Berlex Laboratories, Inc. "Berlex has a rich history in oncology, and the arrival of Campath in the marketplace further demonstrates our commitment to the community of refractory B-CLL patients and caregivers. Campath, the newest product in Berlex's oncology portfolio, represents the most recent advance in CLL therapy."

"This represents a milestone in advancing Millennium's downstream capabilities through strategic partnerships that focus on the development of innovative products directed at unmet medical needs," said Mark Levin, chief executive officer of Millennium. "I am very pleased that the result of our combined efforts means that patients with refractory B-CLL now have a new modality of therapy available to them."

"As a specialist in oncology drugs, ILEX is pleased to have played a key role in the clinical development of this new agent," said Richard L. Love, president and chief executive officer of ILEX. "Monoclonal antibodies are powerful agents in the fight against cancer, and Campath is the first humanized monoclonal antibody indicated for the treatment of B-CLL and will provide a new option for patients who have failed standard therapies."
-end-
The Campath Biologics License Application (BLA) was submitted to FDA on Dec. 23, 1999. Complete review letters for the application were received by Millennium on June 26, 2000, and February 20, 2001. On Dec. 14, 2000, the Oncologic Drugs Advisory Committee (ODAC) to the FDA voted 14 to 1 to recommend the accelerated approval of Campath.

Additionally, a Marketing Authorization Application (MAA) for Campath was submitted in March 2000 to the European Agency for the Evaluation of Medicinal Products (EMEA) and currently is under review.

Campath will be available to patients in early June.

Prescribing information for Campath can be found on the Berlex Website at www.berlex.com., or by calling 1-888-BERLEX-4.

Company Profiles
Committed to developing novel diagnostics and therapeutics that address unmet medical needs, Berlex Laboratories, Inc., the U.S. affiliate of Schering AG, Germany (NYSE: SHR), researches, develops, manufactures, and markets ethical pharmaceuticals in five strategic areas: female healthcare, oncology, diagnostic imaging, dermatology, and therapeutics for life-threatening and disabling diseases. Berlex Laboratories, Inc., (www.berlex.com) has business operations in Montville and Wayne, N.J., and in Richmond, California.

Millennium Pharmaceuticals, Inc., a biopharmaceutical company, applies its comprehensive and integrated science and technology platform for the discovery and development of therapeutic and preventative medicine products. Headquartered in Cambridge, Mass., Millennium currently employs more than 1,200 people.

Founded in 1994 as an oncology drug development company, ILEX Oncology, Inc., is positioned to become a leading oncology-focused pharmaceutical company. Based in San Antonio, Texas, ILEX is advancing a deep pipeline of anti-cancer compounds focused on the treatment of both advanced and early disease. The pipeline comprises multiple technologies at all stages of clinical development, including a monoclonal antibody, apoptosis-inducing agents, cytotoxic compounds with novel mechanisms of action, angiogenesis inhibitors and chemoprevention agents. ILEX maintains in-house development organizations for oncology drugs, in San Antonio, Annapolis, Maryland, and the United Kingdom. ILEX also conducts translational research in angiogenesis inhibition, medicinal chemistry, and nuclear receptor biology from its laboratories in Boston, Massachusetts, and Geneva, Switzerland. Further information about ILEX can be found on the company's web site at www.ilexonc.com.

For Berlex:
Certain statements in this press release that are neither reported financial results nor other historical information are forward-looking statements, including but not limited to, statements that are predictions of, or indicate future events, trends, plans or objectives. Undue reliance should not be placed on such statements because, by their nature, they are subject to known and unknown risks and uncertainties, and can be affected by other factors that could cause actual results, as well as the plans and objectives of Schering AG Germany, or its US affiliate, Berlex Laboratories, Inc., to differ materially from those expressed or implied in the forward-looking statements. Certain factors that may cause such differences are discussed in our Form 20-F registration statement. Schering AG Germany and Berlex Laboratories undertake no obligation to update publicly or revise any of these forward-looking statements, whether to reflect new information or future events or circumstances or otherwise.

For Millennium:
This press release contains "forward-looking statements," including statements about our growth and future operating results, discovery and development of products, potential acquisitions, strategic alliances and intellectual property. Various risks may cause Millennium's actual results to differ materially, including: adverse results in our drug discovery and clinical development processes; failure to obtain patent protection for our discoveries; commercial limitations imposed by patents owned or controlled by third parties; our dependence upon strategic alliance partners to develop and commercialize products and services based on our work; difficulties or delays in obtaining regulatory approvals to market products and services resulting from our development efforts; and the requirement for substantial funding to conduct research and development and to expand commercialization activities. For a further list and description of the risks and uncertainties we face, see the reports we have filed with the Securities and Exchange Commission. We disclaim any intention or obligation to update or revise any forward-looking statements, whether as a result of new information, future events or otherwise.

For ILEX:
For ILEX: Certain statements contained herein, including the statements relating to and the marketing and distribution of Campath, 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, the early stage of the ILEX's compounds under development; risks in technology and product development; failure to successfully complete clinical trials; failure to receive market clearance from regulatory agencies, including the FDA; dependence on third parties and partners and those risks described in ILEX's Form S-3 filed March 8, 2000 (Commission file #333-32000), and ILEX's Annual Report on Form 10-K for the year ended December 31, 2000, and in other filings made by ILEX with the SEC. ILEX disclaims any obligation to update these forward-looking statements.

Contacts:
Berlex Laboratories Inc.
Rich Salem (media):973-487-2371
Joanne Marion (investor):973-487-2164

Millennium Pharmaceuticals Inc.
Maureen Suda (media):617-551-2959
Clare Midgley (investor):617-679-7480

ILEX Oncology Inc.
Jill Scoggins (media):210-949-8687
Ann Stevens (investor):210-949-8230

To schedule interviews
Jeffrey Sholemson:312-856-8805
Chelsea Carlson:212-601-8041

Porter Novelli

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