8 juni 2005: Bron: DOW en British Journal of Haematology

Nadat Velcade goed gekeurd is na fase III studies voor tweede lijns behandelingen van botkanker - Kahler - Multiple Myeloma hebben nu twee gerandomiseerde fase II studies bewezen dat Velcade als eerste lijns ook zeer goede resultaten geeft bij Kahler. Resultaten van een derde fase III studie worden binnen enkele weken bekendgemaakt. Opvallend ook dat een voorbehandeling met Velcade voor veel meer patiënten - bij 20 van de 21 - de mogelijkheid opent voor een stamceltransplantatie of dubbele stamceltransplantatie, de enige behandeling tot nu toe die voor een definiteive genezing van Kahler kan zorgen. Dit zijn echt opzienbarende en zeer hooppgevende resultaten. En heel goed nieuws is dat er in Nederland een grote gerandomiseerde fase III studie in meerdere ziekenhuizen gaat worden uitgevoerd met Velcade als eerste lijns bij 800 deelnemende Kahlerpatiënten. Lees hier ook zeer uitgebreid persbericht uitgegeven dor de DOW vandaag en met dank aan Karel die ons dit allemaal toestuurde.

. -- PRESS RELEASE: Two New Studies in the British Journal of Haematology Show Potential Role of VELCADE(R) (Bortezomib) for Injection in Treating Patients with Front-Line Multiple Myeloma --

CAMBRIDGE, Mass., June 8 /PRNewswire-FirstCall/ -- Millennium Pharmaceuticals, Inc. (Nasdaq: MLNM) today announced publication in The British Journal of Haematology of two phase II studies which showed strong single agent and very high combination response rates in front-line multiple myeloma (MM). Overall response rates ranged from 88 to 95 percent with complete and near complete responses ranging from 25 to 29 percent. Use of VELCADE in the front-line setting allowed for successful stem cell transplants for these patients. A complete and near complete response rate of 57 percent was reported following single stem cell transplant preceded by induction with VELCADE, doxorubicin and dexamethasone (PAD). This response rate was similar to the complete and very good partial response rates previously published for tandem transplants.(1)

The results from these studies add to the growing body of VELCADE front- line data supporting the phase III development program that includes two trials with a third expected to be initiated in the coming weeks. VELCADE, the first of a new class of medicines called proteasome inhibitors, is the first treatment in more than a decade to be approved for patients with MM and is currently approved for the treatment of patients who have received at least one prior therapy. More than 12,000 patients have been treated in the U.S. with VELCADE to date and VELCADE is the only drug therapy to demonstrate a significant survival advantage when compared to a standard treatment in relapsed MM patients.

"These data indicate that earlier use of VELCADE may improve overall response outcomes for multiple myeloma patients," said James Cavenagh, M.D., FRCP, FRCPath, principal investigator of the PAD study at St. Bartholomew's Hospital, West Smithfield, London. "We are extremely excited about these findings as they may offer greater hope for newly diagnosed multiple myeloma patients." VELCADE is being co-developed by Millennium Pharmaceuticals, Inc. and Johnson & Johnson Pharmaceuticals Research & Development L.L.C. (J&JPRD).

VELCADE(R) (bortezomib) for Injection Alone and In Combination with Dexamethasone

The multicenter phase II study, led by Sundar Jagannath, M.D., assessed the efficacy and safety of VELCADE as a single agent and in combination with standard therapy dexamethasone in patients with previously untreated, symptomatic MM. Patients were treated for up to six cycles with VELCADE. Dexamethasone was administered the day of and the day after VELCADE if less than a partial response (PR) after cycle two or less than a complete response (CR) after cycle four was achieved. Patients received a median of six cycles. Response was assessed according to the European Group for Blood and Marrow Transplantation (EBMT) criteria. Results from 32 evaluable patients included:

* Overall response rate (CR+PR) for VELCADE alone or in combination with dexamethasone was 88 percent with a complete and near complete response rate of 25 percent;
* After two cycles of therapy, single agent VELCADE achieved a response rate of 40 percent;
* Six of eight patients who achieved complete or near complete responses did so on VELCADE alone;
* Survival at one year was 87 percent with a median follow-up of 5.5 months; and
* Improved response after the addition of dexamethasone was observed in 68 percent of patients who received dexamethasone

. Stem cell harvesting and engraftment was successful for all transplant patients in this study. Adverse events were reported to be manageable and included gastrointestinal events, neuropathy, myalgia, fatigue, and hematologic toxicities.

PAD Induction Therapy Prior to Stem Cell Transplant

The multicenter phase I/II study, led by Dr. Cavenagh, assessed VELCADE in combination with doxorubicin and dexamethasone (PAD) as induction therapy prior to stem cell transplant in previously untreated MM patients. Four cycles of PAD therapy were administered to patients. Thereafter, patients underwent stem cell mobilization, and the ability to adequately harvest peripheral blood stem cells was evaluated. High-dose melphalan was administered, peripheral blood stem cells were infused, and the rate of hematologic recovery was assessed. Response, based on EBMT criteria, was measured after each cycle of PAD and three months after transplantation. Results from the 21 patients included:

* Overall response rate (CR+PR) was 95 percent with a complete and near complete response rate of 29 percent;
* Stem cell collection was adequate in 20 of 21 patients;
* Eighteen of 20 patients were successfully transplanted as two patients declined transplant;
* Post-transplantation, the overall response rate at three months was 95 percent with a 57 percent complete and near complete response rate; and
* No dose limiting toxicities occurred and adverse events included infections, hyperglycemia, peripheral neuropathy, postural hypotension, gastrointestinal events and atrial fibrillation

. "These data support our pursuit for a front-line indication for VELCADE," said David Schenkein, M.D., senior vice president, clinical research, Millennium. "We, in collaboration with J&JPRD, have initiated a robust phase III program to further evaluate the clinical benefit of VELCADE in front-line multiple myeloma. The first international, multicenter trial, named VISTA and initiated January 2005, is evaluating VELCADE(R) (bortezomib) for Injection in combination with melphalan-prednisone in nontransplant patients. The second trial, the newly initiated HOVON trial, will assess patients who will go on to transplant."

Initiation of the HOVON Phase III Front-Line Trial Millennium, in collaboration with its development partner J&JPRD, supported the recent commencement of a large, multicenter, randomized phase III international trial led by the cooperative group Stichting Hemato- Oncologie voor Volwassenen Nederland (HOVON) in newly diagnosed MM patients. The HOVON clinical trial will assess PAD prior to stem cell transplant followed by maintenance therapy with VELCADE compared to vincristine, adriamycin, and dexamethasone (VAD) as induction therapy prior to transplant with thalidomide maintenance. The study is planning to enroll 800 patients and will compare progression free survival, response rate, survival and the overall safety and tolerability of the two regimens.


VELCADE is indicated for the treatment of multiple myeloma patients who have received at least one prior therapy. VELCADE is contraindicated in patients with hypersensitivity to bortezomib, boron, or mannitol. VELCADE should be administered under the supervision of a physician experienced in the use of antineoplastic therapy.

Risks associated with VELCADE therapy include new or worsening peripheral neuropathy, hypotension, cardiac disorders, gastrointestinal adverse events, thrombocytopenia and tumor lysis syndrome. Women of childbearing potential should avoid becoming pregnant while being treated with VELCADE.

In 331 patients who were treated with VELCADE in a phase III study, the most commonly reported adverse events were asthenic conditions (61%), diarrhea (57%), nausea (57%), constipation (42%), peripheral neuropathy (36%), vomiting (35%), pyrexia (35%), thrombocytopenia (35%), psychiatric disorders (35%), anorexia and appetite decreased (34%), parasthesia (27%), dysesthesia (27%), anemia and headache (26%), and cough (21%). 14% of patients reported at least one episode of grade 4 toxicity; the most common grade 4 toxicities were thrombocytopenia (4%), neutropenia (2%), and hypercalcemia (2%). A total of 144 patients on VELCADE (44%) reported serious adverse events (SAEs) during the study. The most commonly reported SAEs were pyrexia (6%), diarrhea (5%), dyspnea and pneumonia (4%), and vomiting (3%).

VELCADE(R) (bortezomib) for Injection is being co-developed by Millennium Pharmaceuticals, Inc. and Johnson & Johnson Pharmaceutical Research & Development, L.L.C. (J&JPRD). Millennium is responsible for commercialization of VELCADE in the U.S.; Ortho Biotech and Janssen-Cilag are responsible for commercialization in Europe and the rest of the world. Janssen Pharmaceutical K.K. is responsible for commercialization in Japan. VELCADE is approved in 50 countries worldwide, including the U.S., European Union and a number of countries within Latin America and South-East Asia. VELCADE also is approved in the European Union as a second-line treatment. It is indicated as a monotherapy for use in patients with progressive MM who have received at least one prior therapy and who have already undergone or are unsuitable for bone marrow transplantation. Millennium and J&JPRD continue to investigate VELCADE globally in phase I, II and III clinical trials in both hematologic and solid tumors, including front-line MM, non-Hodgkin's lymphoma and lung, prostate and ovarian cancers.

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