FDA Approves VELCADE® (bortezomib) for Injection for Previously Untreated Patients with Mantle Cell Lymphoma
This approval extends the benefit of VELCADE for mantle cell lymphoma (MCL) to previously untreated patients in addition to relapsed or refractory patients
First treatment approved by the U.S. Food and Drug Administration for newly diagnosed MCL patients
Cambridge, Mass., October 9, 2014 – Millennium: The Takeda Oncology Company with its parent company, Takeda Pharmaceutical Company Limited (TSE:4502), today announced that the U.S. Food and Drug Administration (FDA) has approved VELCADE® (bortezomib) for injection for use in previously untreated patients with mantle cell lymphoma (MCL). VELCADE is the first treatment in the United States to be approved for use in previously untreated patients with MCL. This approval extends the utility of VELCADE beyond relapsed or refractory mantle cell lymphoma, for which it has been approved since 2006.
"Mantle cell lymphoma is a subtype of non-Hodgkin lymphoma that is usually a clinically aggressive malignancy, and it is a challenging disease to treat in part due to a relatively high risk of relapse," said Andrew Evens, DO, MSc, Director, Tufts Cancer Center; Chief, Division of Hematology/Oncology; Director, Lymphoma Program. "There are several new targeted drugs approved by the FDA for patients with relapsed or refractory disease, but up to this point, there had been none approved for the treatment of patients with previously untreated disease. VELCADE, when used in the VcR-CAP regimen, VELCADE, rituximab, cyclophosphamide, doxorubicin and prednisone, has demonstrated improved outcomes for patients, making it an important advance for the treatment of newly-diagnosed patients with mantle cell lymphoma."
This approval is based on the results of an international, randomized, head-to-head Phase 3 study that showed that previously untreated patients receiving a VELCADE-containing combination (VcR-CAP) experienced a 59 percent relative improvement in the study's primary endpoint of progression-free survival (PFS) compared to those who were administered the standard R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone) regimen (median 25 vs. 14 months; Hazard Ratio [HR] 0.63; P<0.001) at a median follow up of 40 months. An Independent Review Committee (IRC) assessed the primary efficacy endpoint of PFS. The complete response (CR) rate for patients receiving VcR-CAP vs. R-CHOP was 44 percent vs. 34 percent.
"We are delighted VELCADE has received approval in previously untreated mantle cell lymphoma. The VELCADE-combination delivered an 11-month median advantage in progression-free survival as compared to a current standard of care," said Dixie-Lee Esseltine, MD, FRCPC, Vice President, Oncology Clinical Research, Takeda Pharmaceuticals International Ltd. "Since 2006, VELCADE has proven to be an important therapy for the treatment of relapsed or refractory mantle cell lymphoma, and it can now be used as an initial treatment for all patients with mantle cell lymphoma."
The open-label, multicenter, prospective study evaluated the efficacy and safety of VcR-CAP vs. R-CHOP in 487 patients with previously untreated MCL who were ineligible or not considered for a bone marrow transplant. VELCADE (1.3 mg/m2) is administered intravenously in combination with intravenous rituximab, cyclophosphamide, doxorubicin and oral prednisone (VcR-CAP) for six 3-week treatment cycles. VELCADE is administered first followed by rituximab. VELCADE is administered twice weekly for two weeks (days 1, 4, 8 and 11) followed by a 10‑day rest period on days 12‑21. For patients with a response first documented at cycle 6, two additional VcR-CAP cycles are recommended. At least 72 hours should elapse between consecutive doses of VELCADE.
The most common adverse reactions occurring in ≥20 percent of patients receiving the VcR-CAP regimen were neutropenia, leukopenia, anemia, thrombocytopenia, lymphopenia, peripheral neuropathy, pyrexia, nausea and diarrhea. Infections were reported for 31 percent of patients in the VcR-CAP arm and 23 percent of the patients in the R-CHOP arm including pneumonia (8 percent versus 5 percent). Adverse reactions leading to discontinuation occurred in 8 percent of patients in the VcR-CAP arm and 6 percent of patients in the R-CHOP arm. In the VcR-CAP group, the most commonly reported adverse reaction leading to discontinuation was peripheral sensory neuropathy (1 percent; 3 patients). For additional important safety information, please see below.
About Mantle Cell Lymphoma (MCL)
MCL is a rare, aggressive type of B-cell non-Hodgkin lymphoma (NHL) that usually occurs in older adults. MCL constitutes about 6 percent of cases of NHL. The disease typically begins in the lymph nodes but can spread to other tissues, such as bone marrow and liver. The expected overall survival for MCL is approximately four to five years, and the five-year survival rate for advanced stage MCL is approximately 50 percent.
VELCADE® (bortezomib) is co-developed by Millennium/Takeda and Janssen Pharmaceutical Companies. Millennium is responsible for commercialization of VELCADE in the U.S.; Janssen Pharmaceutical Companies are responsible for commercialization in Europe and the rest of the world. Takeda Pharmaceutical Company Limited and Janssen Pharmaceutical K.K. co-promote VELCADE in Japan. VELCADE is approved in the U.S. for the treatment of mantle cell lymphoma (MCL) as well as in 53 additional countries for the treatment of patients with MCL who have received at least one prior treatment. VELCADE is also approved in more than 90 countries for the treatment of patients with multiple myeloma (MM) and has been used to treat more than 550,000 patients worldwide.
VELCADE: Important Safety Information
Patients should not receive VELCADE if they are allergic to bortezomib, boron or mannitol. VELCADE should not be administered intrathecally. Women should avoid becoming pregnant or breastfeeding while taking VELCADE. Patients with diabetes may require close monitoring and adjustment of their medication. VELCADE can cause serious side effects, including:
· Peripheral neuropathy. Nerve problems, which can be severe including muscle weakness, tingling, burning, pain, or loss of feeling in the hands and feet.
· Low blood pressure. A drop in blood pressure resulting in dizziness, light headedness or fainting.
· Heart problems. Heart rhythm problems and heart failure including worsening of existing conditions. Symptoms may include chest pressure or pain, palpitations, swelling of the ankles or feet, or shortness of breath.
· Lung problems, some of which have been fatal. Symptoms include cough, shortness of breath, wheezing or difficulty breathing.
· Liver problems. Liver failure including a yellow discoloration of the eyes and skin.
· Posterior reversible encephalopathy syndrome (PRES). A rare, reversible condition involving the brain. Symptoms may include seizures, high blood pressure, headaches, tiredness, confusion, blindness, or other vision problems
· Gastrointestinal problems. Nausea, vomiting, diarrhea and constipation.
· Thrombocytopenia and neutropenia. Lowering the levels of blood cells, which could result in a higher risk for infections or bleeding.
· Tumor lysis syndrome (TLS). TLSis a syndrome that causes a chemical imbalance in the blood that could lead to heart and/or kidney problems.
Other common side effects seen in patients receiving VELCADE include: fever, decreased appetite, fatigue, rash.
These are not all of the possible side effects with VELCADE. Please see the full Prescribing Information for VELCADE available at www.VELCADE.com.
About Millennium: The Takeda Oncology Company
Millennium: The Takeda Oncology Company, a leading biopharmaceutical company with its Global Oncology Business Unit based in Cambridge, Mass., markets a first-in-class proteasome inhibitor and has a robust pipeline of oncology product candidates. Additional information about Millennium is available through its website, www.millennium.com.
Located in Osaka, Japan, Takeda is a research-based global company with its main focus on pharmaceuticals. As the largest pharmaceutical company in Japan and one of the global leaders of the industry, Takeda is committed to strive towards better health for patients worldwide through leading innovation in medicine. Additional information about Takeda is available through its corporate website, www.takeda.com.
Editors' Note: This press release is also available under the Media section of the Company's website at: www.millennium.com/InTheNews.aspx.
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