FDA Approves Velcade (Bortezomib) for Injection for Aggressive Form of Non-Hodgkin’s Lymphoma

First drug approved for the treatment of patients with mantle cell lymphoma who have received at least one prior therapy

CAMBRIDGE, Mass., December 8, 2006 -- Millennium Pharmaceuticals, Inc. today announced that the U.S. Food and Drug Administration (FDA) has granted full approval of Velcade for the treatment of patients with mantle cell lymphoma (MCL) who have received at least one prior therapy. MCL is a relatively uncommon and aggressive form of non-Hodgkin’s lymphoma for which there was no standard of care in the relapsed or refractory setting. MCL has a U.S. prevalence of 10,000 patients. Velcade is currently the market leader in multiple myeloma (MM) for patients who have received one prior therapy. Today’s approval marks the first indication for Velcade in lymphoma, the most common blood cancer.

"Mantle cell lymphoma is the most challenging lymphoma to treat because it is commonly resistant to chemotherapy in the relapsed setting," said Andre Goy, M.D., Chief of The Division of Lymphoma, The Cancer Center at Hackensack University Medical Center in Hackensack, N.J. "This approval offers new hope for patients with mantle cell lymphoma who have received at least one prior therapy."

"Velcade is the first drug to receive FDA approval in relapsed mantle cell lymphoma and is based upon the data from our Phase II trial. This represents a new option for patients and a significant milestone for Millennium," said Deborah Dunsire, M.D., President and CEO, Millennium. "In conjunction with our co-development partner, Johnson & Johnson Pharmaceutical Research & Development (J&JPRD), Velcade is also being investigated in clinical studies in patients with newly diagnosed multiple myeloma and additional types of non-Hodgkin’s lymphoma."

The approval is based on data from the PINNACLE trial, the largest study to date in patients with MCL. PINNACLE was a prospective, multi-center, single-arm, open-label study in patients with MCL whose disease progressed following at least one prior therapy. Response rates to Velcade were determined according to the International Workshop Response Criteria (IWRC) and based on independent radiologic review of CT scans. Results of the study, which formed the basis of the approval, include:

  • Overall response rate of 31 percent
  • Complete response (CR + CRu) rate of 8 percent
  • Median duration of response of 9.3 months; 15.4 months in patients achieving a complete response
  • Median time to progression of 6.2 months

In PINNACLE, the most commonly reported adverse events were asthenic conditions (72%), peripheral neuropathy (55%), constipation (50%), diarrhea (47%), nausea (44%), decreased appetite (39%), rash (28%), edema (28%), vomiting (27%), dizziness (23%), dyspnea (23%), insomnia (21%) and thrombocytopenia (21%).

Velcade is now being studied by two U.S. cooperative groups. The first study, conducted by the Southwest Oncology Group (SWOG), is in the frontline setting. The second study, conducted by the Cancer and Leukemia Group B (CALGB), is evaluating the combination with R-CHOP as consolidation or maintenance following transplant. Earlier this year, Millennium and co-development partner, Johnson & Johnson Pharmaceutical Research & Development, L.L.C. (J&JPRD), initiated an international Phase III clinical trial with Velcade in combination with rituximab in patients with relapsed or refractory follicular lymphoma, another subtype of non-Hodgkin’s lymphoma. Additionally, more than 170 clinical trials with Velcade are ongoing in various disease settings, both company sponsored and investigator initiated.

Velcade is also approved for the treatment of patients with MM who have received at least one prior therapy. Velcade is the first and only single agent to provide a survival benefit in patients with relapsed multiple myeloma. To date, more than 50,000 patients, including individuals in clinical trials, have been treated with Velcade in more than 75 countries.

About Non-Hodgkin’s Lymphoma and Mantle Cell Lymphoma

Non-Hodgkin’s lymphoma (NHL) is the most common hematological cancer, the fifth leading cause of cancer death and the second fastest growing form of cancer in the U.S.(1) The prevalence of NHL in the U.S. is approximately 400,000 patients, 77,000 patients with follicular lymphoma and 10,000 with mantle cell lymphoma. There are approximately 54,000 new cases of NHL diagnosed in the U.S. per year, and 19,000 deaths are attributed to the disease annually(1-4).

Mantle cell lymphoma is an aggressive, rapidly progressive subtype of NHL, and is not curable with standard treatment. The median life expectancy for a patient with MCL following first relapse is 1-2 years.

About Velcade

Velcade is being co-developed by Millennium Pharmaceuticals, Inc. and Johnson & Johnson Pharmaceutical Research & Development, L.L.C. Millennium is responsible for commercialization of Velcade in the U.S.; Janssen-Cilag is responsible for commercialization in Europe and the rest of the world in multiple myeloma. Janssen Pharmaceutical K.K. is responsible for commercialization in Japan. For a limited period of time, Millennium and Ortho Biotech Inc. will co-promote Velcade in the U.S. Velcade also is approved in the European Union after first relapse.

Velcade (bortezomib) for Injection is indicated for the treatment of patients with multiple myeloma who have received at least one prior therapy. Velcade (bortezomib) for Injection is indicated for the treatment of patients with mantle cell lymphoma 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 observed throughout therapy, cardiac and pulmonary disorders, gastrointestinal adverse events, thrombocytopenia, neutropenia and tumor lysis syndrome. Women of childbearing potential should avoid becoming pregnant while being treated with Velcade. Cases of severe sensory and motor peripheral neuropathy have been reported. The long-term outcome of peripheral neuropathy has not been studied in mantle cell lymphoma. Acute development or exacerbation of congestive heart failure, and/or new onset of decreased left ventricular ejection fraction has been reported, including reports in patients with few or no risk factors for decreased left ventricular ejection fraction. There have been rare reports of acute diffuse infiltrative pulmonary disease of unknown etiology such as pneumonitis, interstitial pneumonia, lung infiltration and Acute Respiratory Distress Syndrome (ARDS) in patients receiving Velcade. Some of these events have been fatal. A higher proportion of these events have been reported in Japan. There have been rare reports of RPLS in patients receiving Velcade. RPLS is a rare, reversible, neurological disorder which can present with seizure, hypertension, headache, lethargy, confusion, blindness, and other visual and neurological disturbances. Velcade is associated with thrombocytopenia and neutropenia. There have been reports of gastrointestinal and intracerebral hemorrhage in association with Velcade. Transfusions may be considered. Complete blood counts (CBC) should be frequently monitored during treatment with Velcade. Rare cases of acute liver failure have been reported in patients receiving multiple concomitant medications and with serious underlying medical conditions.

Safety Data: In 1163 patients in MM and MCL studies, the most commonly reported adverse events were asthenic conditions (64%), nausea (55%), diarrhea (52%), constipation (41%), peripheral neuropathy (39%), thrombocytopenia (36%), appetite decreased, including reports of anorexia (36%), pyrexia (34%), vomiting (33%) and anemia (29%). Twenty percent of patients experienced at least one episode of grade 4 toxicity; the most common grade 4 toxicities were thrombocytopenia (5%) and neutropenia (3%). Fifty percent of patients reported serious adverse events (SAEs). The most commonly reported SAEs were pneumonia (7%), pyrexia (6%), diarrhea (5%), vomiting (4%), and nausea, dehydration, dyspnea and thrombocytopenia (each 3%).

For more information about Velcade clinical trials, patients and physicians can contact the Millennium Medical Product Information Department at 1-866-Velcade (1-866-835-2233).

Source: Millennium Pharmaceuticals, Inc.

References:
(1) Jemal, A. CA Cancer J Clin. 2006 Mar-Apr;56(2):106-30.
(2) Mantle Cell Lymphoma. 01 June 2006. Lymphoma Information Network. 27 Oct 2006 http://www.lymphomainfo.net/nhl/types/mantle.html
(3) Non-Hodgkin’s Lymphoma. Onkos Study #52. February 2002;12. Decision Resources, Inc.
(4) Data on File

Posted: December 2006


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