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New Data From Velcade(TM) For Injection Crest Study Indicate Responses In Patients With MM
12.09.02

12/09/2002

PR Newswire
(Copyright (c) 2002, PR Newswire)
-- Complements Summit Study In Earlier Stage Of Disease --

PHILADELPHIA, PA, Dec. 9 /PRNewswire-FirstCall/ -- Millennium Pharmaceuticals, Inc. (Nasdaq: MLNM) today announced final results of the phase II CREST study (previously known as 024) for its investigational cancer drug VELCADE in the treatment of patients with multiple myeloma whose cancer had relapsed following front-line treatment. The study also evaluated the response to VELCADE in combination with dexamethasone in patients not responding to VELCADE alone. The results, presented today at the 44th annual meeting of the American Society of Hematology, indicated consistent clinical activity of VELCADE at two treatment doses, including complete remissions, and a possible dose effect for both clinical response and adverse events.

"These data add to the emerging picture of clinical activity with VELCADE," said principal investigator Sundar Jagannath, MD, from St. Vincent's Catholic Medical Center in New York, NY. He explained that researchers often first determine if a cancer drug is active in patients with the most advanced disease and who have few treatment options. This research approach was demonstrated in the phase II SUMMIT study, presented earlier today, for which final data indicated that the majority of patients experienced a response or achieved stable disease when treated with VELCADE; these patients had relapsed and were refractory despite receiving multiple, prior therapies. "These new findings suggest that VELCADE may also benefit patients who have relapsed following fewer prior treatments," he said.

Study and findings

The multi-center phase II study included 54 patients with multiple myeloma whose disease had relapsed after front-line therapy. Patients in the trial had a median of one prior line of therapy, which may have included multiple different treatment regimens. Overall, 98 percent had received prior steroid therapy, 72 percent prior alkylating agents, 50 percent prior anthracyclines, 48 percent prior stem cell transplantation and 30 percent prior thalidomide. During the trial, patients were randomized to receive either 1.0 mg/m2 or 1.3 mg/m2 of VELCADE(TM) (bortezomib) for Injection therapy for up to 24 weeks (days 1, 4, 8 and 11 of a 21-day cycle, for up to eight cycles). After two or four cycles of VELCADE alone, patients not responding were treated with VELCADE plus dexamethasone, a conventional therapy.

Responses were assessed using Blade criteria - a rigorous assessment standard used to describe changes in disease status, including a confirmation six weeks later. A "complete response" required 100 percent disappearance of M-protein (a marker of tumor burden); negative immunofixation testing; less than five percent plasma cells in the bone marrow; no increase in size or number of lytic bone lesions; and disappearance of soft tissue tumors (plasmacytomas). "Partial" remissions and "minimal" responses represented lesser degrees of response based on the same criteria. Worsening of these indicators constituted "progressive disease." Importantly, these determinations of response were confirmed by an independent review committee (IRC).

Study results from the 1.3 mg/m2 treatment group (n=26) were as follows:

  • Complete remissions in four percent of patients as determined by Blade criteria.
  • The overall response rate was 50 percent. Overall response was defined as the combined total of complete and partial remissions and minimal responses.
  • Overall, 69 percent of patients experienced a response or achieved stable disease.
  • When dexamethasone was added to the treatment of patients who were not responding to 1.3 mg/m2 of VELCADE alone, the overall response rate increased from 50 percent to 62 percent.

Study results from the 1.0 mg/m2 treatment group (n=27) were as follows:

  • Complete remissions in four percent of patients as defined by Blade criteria and an additional seven percent who had a 100 percent reduction in M-protein but a positive immunofixation test (a sensitive antibody test for trace amounts of M-protein).
  • The overall response rate was 33 percent. Overall response was defined as the combined total of complete and partial remissions and minimal responses.
  • Overall, 59 percent of patients experienced a response or achieved stable disease.
  • When dexamethasone was added to the treatment of patients who were not responding to 1.0 mg/m2 of VELCADE alone, the overall response rate increased from 33 percent to 44 percent. The overall median time to progression was 11 months. The overall median survival for the combined treatment groups had not been reached at 8.8 months of follow up.

VELCADE(TM) (bortezomib) for Injection was generally well-tolerated and adverse events were manageable and predictable. The most commonly reported adverse events were gastrointestinal-related, including nausea, diarrhea, constipation, and vomiting, as well as thrombocytopenia, peripheral neuropathy, neutropenia, fatigue, anorexia, pyrexia and anemia. There appeared to be differences in the frequency of adverse events between the 1.0 mg/m2 and 1.3 mg/m2 treatment groups, particularly in the case of peripheral neuropathy (18 percent versus 58 percent), which is being further evaluated in the ongoing phase III APEX trial in patients who require a dose reduction due to adverse events.

"While this study was not statistically powered to compare the safety and efficacy of VELCADE (bortezomib) for Injection at two different doses, we are pleased that the results are consistent with those seen in our major phase II SUMMIT trial," said Barry Greene, general manager, oncology, at Millennium.

APEX, an international, multi-center phase III trial of VELCADE versus high-dose dexamethasone in patients with relapsed or refractory multiple myeloma, began in June 2002 for patients who have received one-to-three previous therapies. Phase I and II trials of VELCADE in various types of solid tumors are underway.

About Multiple myeloma

Multiple myeloma is a cancer of the bone marrow in which white blood cells called plasma cells, normally responsible for the production of antibodies (proteins that fight infection and disease), are overproduced. The proliferation of these abnormal plasma cells, known as myeloma cells, causes decreased production of normal red and white blood cells, and of normal disease-fighting antibodies, as well as the growth of tumors that spread to multiple sites - hence the term multiple myeloma. The decreased white blood cell production damages the immune system while the myeloma tumors cause bone destruction that manifests as pain and fractures.

Multiple myeloma is the second most common hematologic malignancy and although the disease is predominantly a cancer of the elderly (the average age of onset is 65 to 70 years of age), recent statistics indicate both increasing incidence and younger age of onset. In the United States, more than 40,000 individuals have multiple myeloma and over 14,000 new cases of the disease are diagnosed each year.(1) Worldwide there are approximately 74,000 new cases and over 45,000 deaths due to multiple myeloma each year.(2)

The Millennium Oncology Franchise

Millennium is committed to pursuing oncology as a core franchise area, dedicating significant resources and capabilities in the areas of technology, scientific expertise, clinical development, and strategic business development. To this end, Millennium is focused on leveraging its expertise in kinases, the proteasome pathway, and targeting monoclonal antibodies, and has already produced a deep pipeline that ranges from multiple novel targets to a commercialized therapeutic product. Current clinical programs include VELCADE(TM) (bortezomib) for Injection, an investigational, first-in-class small molecule designed to inhibit the proteasome. Among the most advanced clinical compounds in addition to VELCADE are MLN518, MLN591RL, MLN2704 and MLN576 (XR11576). Campath(R) (alemtuzumab), a therapeutic developed from a former joint venture of Millennium and ILEX Oncology, Inc., is commercially available in the United States and a number of European countries.

About Millennium

Millennium Pharmaceuticals, Inc., a leading biopharmaceutical company, co- promotes INTEGRILIN(R) (eptifibatide) Injection, a market leading therapy for patients with acute coronary syndrome, and has a robust clinical development pipeline of product candidates. The Company's research, development and commercialization activities are focused in four disease areas: cardiovascular, oncology, inflammation and metabolic. By applying its knowledge of the human genome, its leading understanding of disease mechanisms, and its industrialized technology platform, Millennium is developing breakthrough personalized medicine products. Headquartered in Cambridge, Mass. Millennium also has facilities in South San Francisco, Calif. and Cambridge, UK.

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 the Company'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; the commercial success of INTEGRILIN(R) (eptifibatide) Injection; our ability to extinguish the convertible notes assumed in the COR acquisition; 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.

CAMPATH(R) is a registered trademark of ILEX Pharmaceuticals, L.P.

Editors' Note: This release is also available on the Company's website at: www.millennium.com

  1. Multiple Myeloma Research Foundation. Myeloma Basics: The Statistics.
    http://www.multiplemyeloma.org/aboutmyeloma/statistics.html
  2. Cancer Mondial; International Agency for Research on Cancer, World Health Organization; J. Ferlay, F. Bray, P. Pisani and D.M. Parkin.
    GLOBOCAN 2000: Cancer Incidence, Mortality and Prevalence Worldwide, 2001; http://www-dep.iarc.fr/dataava/interp.htm


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