77 Per Cent of Multiple Myeloma Patients Showed Reduction or Stabilisation in Myeloma -M- Protein Levels in Preliminary Phase II Data for Proteasome Inhibitor Bortezomib.

Business Editors & Health/Medical Writers

NICE, France--(BUSINESS WIRE)--Oct. 20, 2002

Millennium Pharmaceuticals, Inc. (NASDAQ:MLNM):

-- Investigational Compound Halted Disease Progression and Reduced Tumor Burden in Patients Whose Condition Had Progressed After Multiple Prior Therapies

Millennium Pharmaceuticals, Inc. (Nasdaq:MLNM) today announced updated preliminary findings of a phase II clinical trial of its investigational drug bortezomib in patients with multiple myeloma, the second most common haematologic cancer, whose disease has relapsed and not responded following multiple prior treatments.

The study results showed that bortezomib (formerly known as MLN341, LDP-341 and PS-341) stabilised or reduced myeloma (M) protein (a primary marker of cancer burden) in 77 per cent of patients in the trial evaluated at this time. Side effects were manageable and predictable. In addition, the majority of patients did not experience disease progression during the 24-week study. The results were presented for the first time in Europe at a symposium today at the annual meeting of the European Society of Medical Oncology (ESMO) in Nice, France.

"Proteasome inhibition is a totally new potential approach to treating multiple myeloma and the preliminary results of this trial are very encouraging," commented Dr. Graham Jackson, Consultant Haematologist, Royal Victoria Hospital, Newcastle Upon Tyne, England. "Whilst the development of treatments has progressed in recent years, mortality rates are still very high for people with multiple myeloma.

Patients in this trial had failed many therapies including transplantation so it is promising that the majority of patients treated with bortezomib experienced stabilisation of their disease or even regression with manageable side effects suggesting that proteasome inhibition may play an important role in the future treatment of multiple myeloma."

Bortezomib was designed to specifically inhibit the proteasome, which is an enzyme complex in the cell responsible for breaking down a variety of proteins, including many that regulate cell division. Laboratory studies suggest that inhibition of the proteasome by bortezomib disrupts regulation of cancer cell regulatory processes and ultimately induces apoptosis (programmed cell death). While healthy cells appear to be able to recover from the effects of proteasome inhibition in these studies, cancer cells seem to be more sensitive to its pro-apoptotic effects. Therefore, proteasome inhibition with bortezomib may be an effective way of targeting cancer cells while sparing healthy ones.

About the study

Bortezomib - the only proteasome inhibitor in clinical trials for oncology - has been evaluated in over 900 cancer patients in clinical trials to date. The study reported at ESMO included the first 78 patients treated in this phase II trial of patients with refractory and relapsing multiple myeloma who had received at least two to four prior therapies and who were experiencing progressive disease while on their most recent therapy. Bortezomib was given to the patients for up to 24 weeks. Among these patients, there was an average of five prior therapeutic regimens for their cancer, including over 70 per cent who previously received thalidomide, over 50 per cent who had received high dose chemotherapy requiring stem cell transplantation, and over 90 per cent who had received prior dexamethasone or other steroid therapy.

Study results from the first 78 patients included the following:

-- 77 per cent of patients receiving bortezomib experienced a reduction or stabilisation in their M protein, a substance in the blood used by physicians to evaluate multiple myeloma tumor burden;

- Specifically, 20 per cent (14 out of 70 evaluable patients) had a greater than 90 per cent reduction in their M protein levels;

- 47 per cent of patients (33 out of 70 evaluable patients) had at least a 25 per cent reduction;

-- Overall, 77 per cent of patients (54 of 70 evaluable patients) in the study experienced stabilisation of the disease or a reduction in their M protein levels after receiving bortezomib for up to 24 weeks;

-- Overall, for the population in this study, the median time to progressive disease (TTP) had not been reached after 6.2 months of follow-up, with the majority of patients still not experiencing progressive disease.

Side effects with bortezomib were manageable and predictable and included nausea, fatigue, diarrhea, headache, decreased platelets, and peripheral neuropathy (numbness, tingling and pain in the extremities). Many of the patients had received prior therapies that affect the blood, bone marrow and the nervous system.

Approximately 80 per cent of patients entered the trial with baseline neuropathy. Overall, 21 per cent of patients in the study discontinued due to adverse events, including 2.6 per cent (2 patients) due to neuropathy. There was no hair loss or apparent increase in infection risk as often is seen with patients on chemotherapy. Patients with many of the complications of multiple myeloma, such as anemia, thrombocytopenia and reduction in kidney function, including patients on dialysis, tolerated therapy with bortezomib.

"These findings are a significant advance in our development of bortezomib which could provide hope to many seriously ill patients with multiple myeloma," said Barry Greene, general manager, oncology, at Millennium Pharmaceuticals. "Because of the potential broad applicability of its unique mechanism of action, inhibition of the proteasome, bortezomib is also being actively pursued in clinical studies for solid tumors including colon, lung, breast, prostate and pancreatic cancers."

Data from on the full cohort of 202 patients from this study will be presented at the annual meeting of the American Society of Hematology, December 6-10 in Philadelphia, PA. In addition, investigators will present results of a study of bortezomib treatment in patients with myeloma who have relapsed following one previous therapy. An international, multi-center phase III trial of bortezomib versus high dose dexamethasone in patients with refractory multiple myeloma began in June for patients who have received one to three previous therapies.

About multiple myeloma

Multiple myeloma is a cancer of the blood in which white blood cells called plasma cells, normally responsible for the production of antibodies (proteins that fight infection and disease), are overproduced in the bone marrow - the tissue inside the bone that manufactures all blood cells. 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 cancer of the blood 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. Every year, there are almost 19,000 new cases and over 14,000 deaths from multiple myeloma in the European Union. Worldwide there are approximately 74,000 new cases and over 45,000 per annum1.

Millennium's 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 and strategic business development. To this end, Millennium has already produced a deep oncology pipeline that ranges from multiple novel targets to commercialised therapeutic and diagnostic products.

Among the most advanced clinical compounds in addition to bortezomib and MLN518, MLN591, an anti-PSMA antibody currently in phase I clinical trials for advanced prostate cancer and MLN576 (XR11576), a small molecule with DNA-targeting activity in phase I trials for solid tumors. The monoclonal antibody alemtuzumab, (US brand name Campath(R), EU brand name MabCampath(R)), a therapeutic developed from a former joint venture of Millennium and ILEX Oncology, Inc., is commercially available in both the United States and a number of European countries. A Millennium alliance partner and licensee is in the process of developing and commercialising Melastatin(R), a melastatin detection product for melanoma developed through our predictive medicine efforts.

About Millennium

Millennium Pharmaceuticals, Inc., a leading biopharmaceutical company, markets INTEGRILIN(R), a leading therapy in cardiovascular disease, and has a robust clinical development pipeline of breakthrough product candidates. The Company's research, development and commercialisation activities are focused in four therapeutic areas: oncology, cardiovascular, inflammatory and metabolic diseases. By applying its knowledge of the human genome, its leading understanding of disease mechanisms, and its industrialised technology platform, Millennium is developing breakthrough personalised medicine products. Headquartered in Cambridge, Mass., Millennium also has facilities in San Francisco 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 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 first parties; our dependence upon strategic alliance partners to develop and commercialise products and services based on our work; difficulties or delays in obtaining regulatory approvals to market products and services resulting from our development efforts; realising the expected benefits our acquisition of COR Therapeutics, Inc. and successfully integrating COR into our company; the commercial success of INTEGRILIN(R); 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 commercialisation 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.

Editors note: this press release also is available online at www.millennium.com

Campath(R) and MabCampath(R) are registered trademarks of ILEX Pharmaceuticals, L.P.

1. 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