CAMBRIDGE, Mass.–(BUSINESS WIRE)–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 a supplemental new drug application (sNDA) for VELCADE®(bortezomib), which updates the label to include the subcutaneous method of administration in all approved indications: multiple myeloma and mantle cell lymphoma after at least one prior therapy.

“The consistency in efficacy findings, and observed differences in peripheral neuropathy, allow physicians to tailor VELCADE treatment for their patients.”

The approval was based on results from a randomized, phase 3, open-label, international, non-inferiority trial conducted in 222 bortezomib-naïve patients with relapsed multiple myeloma (MM). The primary (non-inferiority) objective of the trial was to demonstrate that single agent subcutaneous VELCADE retained at least 60 percent of the overall response rate (ORR) after 4 cycles relative to single agent intravenous VELCADE. Patients in both arms who did not obtain an optimal response (less than complete response (CR)) to therapy with VELCADE alone after 4 cycles were allowed to receive 20 mg of oral dexamethasone daily on the day of and after VELCADE administration. The secondary endpoints of the study included safety and tolerability, ORR and CR rate after 8 cycles, time to progression (TTP), progression free survival (PFS), and one-year overall survival (OS) of the two routes of administration.

Subcutaneous Administration

The pivotal study, published in the Lancet Oncology in May 2011, met its primary efficacy endpoint. Patients receiving VELCADE subcutaneously achieved a 4-cycle ORR of 43 percent and CR rate of 7 percent, while patients receiving VELCADE intravenously achieved an ORR of 42 percent and a CR rate of 8 percent. The overall safety profile was similar between the two arms. however, differences were observed in the incidence of peripheral neuropathy (PN). in the subcutaneous arm of the trial, 6 percent of patients experienced PN of grade 3 or higher, compared with 16 percent in the intravenous arm. in the subcutaneous arm, 38 percent of patients experienced PN of all grades, compared with 53 percent of patients in the intravenous arm.

“Subcutaneous VELCADE is yet another advance in the management of patients with multiple myeloma or relapsed mantle cell lymphoma,” said Karen Ferrante, M.D., Chief Medical Officer, Millennium. “The consistency in efficacy findings, and observed differences in peripheral neuropathy, allow physicians to tailor VELCADE treatment for their patients.”

“Considering this new subcutaneous route of administration for VELCADE is important for our patients, including those with poor vein access and those with pre-existing peripheral neuropathy or a high risk of developing peripheral neuropathy,” said Noopur Raje, M.D. director of the Center for Multiple Myeloma at Massachusetts General Hospital Cancer Center. “It’s important to have a range of treatment options to provide the best possible care to each individual patient.”

Additional study results at 8 cycles of treatment for subcutaneous and intravenous VELCADE, respectively, included:

• ORR 53 percent and 51 percent
• CR rate 11 percent and 12 percent

Additional study results at 11.8-month median follow-up for subcutaneous and intravenous VELCADE, respectively, included:

• TTP 10.4 months and 9.4 months
• PFS 10.2 months and 8.0 months
• OS at 1 year 72.6 percent and 76.7 percent

Grade 3 and above adverse events with differences greater than 5 percent between routes of administration were:

• Peripheral neuropathy, subcutaneous 6 percent, intravenous 16 percent
• Thrombocytopenia, subcutaneous 13 percent, intravenous 19 percent
• Neuralgia, subcutaneous 3 percent, intravenous 9 percent

New Contraindication for Intrathecal Administration

The updated label also includes a contraindication for intrathecal administration as fatal events have occurred with the inadvertent intrathecal administration of VELCADE. VELCADE is for intravenous or subcutaneous use only.

About VELCADE

VELCADE is co-developed by Millennium 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 more than 90 countries and has been used to treat more than 300,000 patients worldwide.

Important Safety Information

VELCADE® (bortezomib) is approved for the treatment of patients with multiple myeloma. VELCADE is also approved for the treatment of patients with mantle cell lymphoma who have already received at least one prior treatment.

Patients should not receive VELCADE if they are allergic to bortezomib, boron or mannitol. VELCADE should not be administered intrathecally. Women should be advised not to take VELCADE while pregnant or breast-feeding. Patients with diabetes may require close monitoring and adjustment of their medication.

VELCADE can cause serious side effects, including:

• Nerve problems, which can be severe, including muscle weakness, tingling, burning, pain, or loss of feeling in the hands and feet.
• A drop in blood pressure resulting in dizziness, light headedness or fainting.
• 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 disorders, some of which have been fatal. Symptoms include cough, shortness of breath, wheezing or difficulty breathing.
• Nausea, vomiting, diarrhea and constipation.
• Lowering the levels of blood cells, which could result in a higher risk for infections or bleeding.
• Tumor lysis syndrome and reversible posterior leukoencephalopathy syndrome have been reported.
• Liver failure including a yellow discoloration of the eyes and skin.

Common side effects seen in patients receiving VELCADE include: fever, decreased appetite, fatigue, insomnia and headache.

These are not all of the possible side effects with VELCADE. Please see the full Prescribing Information for VELCADE for a complete list also available at VELCADE.com.

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).

Editors’ Note: This press release is also available under the Media section of the Company’s website at: millennium.com/InTheNews.aspx.

About Millennium

Millennium: The Takeda Oncology Company, a leading biopharmaceutical company based in Cambridge, Mass., markets VELCADE, a first-in-class proteasome inhibitor, and has a robust clinical development pipeline of product candidates. Millennium Pharmaceuticals, Inc. was acquired by Takeda Pharmaceutical Company Ltd. in May, 2008. The Company’s research, development and commercialization activities are focused in oncology. Additional information about Millennium is available through its website, millennium.com.

About Takeda

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, takeda.com.

June 06, 2011 03:57 PM Eastern Daylight Time 

– Data show overall response rates of 55 percent; 37 percent in VELCADE refractory patients –

2011 ASCO Annual Meeting

CAMBRIDGE, Mass.–(BUSINESS WIRE)–Millennium: the Takeda Oncology Company with its parent company Takeda Pharmaceutical Company Limited (TSE:4502) today reported results from two studies of VELCADE® (bortezomib) for Injection based combinations in patients with relapsed or refractory multiple myeloma (MM). the first study investigated the safety and efficacy of VELCADE in combination with LY2127399, a human monoclonal antibody. the second study assessed the safety and efficacy of VELCADE in combination with panobinostat. These data were presented at the annual meeting of the American Society of Clinical Oncology, held June 3 through 7 in Chicago, Illinois.

“These two studies provide encouraging evidence of VELCADE’s utility as a backbone for novel combinations”

“These two studies provide encouraging evidence of VELCADE’s utility as a backbone for novel combinations,” said Nancy Simonian, M.D., Chief Medical Officer, Millennium. “We are especially pleased to see activity from VELCADE based combinations in these heavily pre-treated patient populations, including those who were refractory to VELCADE.”

Phase I study of LY2127399, a human anti-BAFF antibody, and bortezomib in patients with previously treated multiple myeloma

the primary objective of this Phase I study in 20 patients was to identify an efficacious dose of LY2127399 with VELCADE. Sixty-five percent of patients had received prior treatment with VELCADE. the results, which were presented by Noopur Raje, M.D., Massachusetts General Hospital, showed:

• the median number of cycles completed was 5, and no dose-limiting toxicities (DLTs) were observed
• the 100 mg dose of LY was selected for further study with VELCADE
• the most common grade 3/4 adverse events were thrombocytopenia (15 percent), neutropenia (10 percent), diarrhea (10 percent) and neuropathy (10 percent)
• Overall response rate (ORR) was 55 percent
• Ten percent of patients achieved a complete response (CR), 15 percent of patients achieved a very good partial response (VGPR) and 30 percent of patients achieved a partial response (PR)
• the median duration of response was 9.7 months

VELCADE was given at 1.3 mg/m2 IV on days 1, 4, 8, and 11 q21d and LY at 1, 10, 30, 100, or 300 mg IV (30 min) on day 1 in Cycles 1 – 3, and every other cycle thereafter. Corticosteroids were not allowed. Response was assessed per IMWG criteria and adverse events per CTCAE v3.0. Pharmacokinetics (PK) were assessed, and pharmacodynamic studies included B-cell immunophenotyping and serum markers of bone turnover. (Abstract #8012)

A phase Ib study of oral panobinostat and IV bortezomib in relapsed and refractory multiple myeloma

this Phase Ib study of 62 relapsed or relapsed and refractory multiple myeloma patients assessed the safety and efficacy of VELCADE in combination with panobinostat. Forty-five percent of patients had received prior treatment with VELCADE, and 31 percent were refractory to VELCADE. the results, which were presented by Jesus San Miguel, M.D., Ph.D., Hospital Universitario de Salamanca, showed:

• Maximum tolerated dose was established as 20 mg of panobinostat plus 1.3 mg/m2 of VELCADE
• the most common grade 3/4 adverse events were thrombocytopenia (79 percent), neutropenia (55 percent) and leukopenia (30 percent)
• across all dosing cohorts, ORR was 55 percent
• among VELCADE-refractory patients, ORR was 42 percent

this phase Ib study of relapsed or relapsed and refractory multiple myeloma completed enrollment (N=62) in Dec 2010 with 47 patients in the dose escalation phase and 15 patients in the dose expansion phase. in the dose escalation phase panobinostat was dosed orally 3 times/week (wk) in combination with VELCADE (IV Days 1, 4, 8, 11) in 21-day cycles (C). Dexamethasone was added for suboptimal response from C2 onwards. MTD was determined to be 20 mg panobinostat and 1.3 mg/m2 VELCADE. in the expansion phase, 15 patients received the MTD of panobinostat and VELCADE, with a modified panobinostat schedule (2 weeks on, 1 week off) and dexamethasone introduced for all patients at C2. this is identical to the dose and schedule in the ongoing phase II and III PANORAMA trials. (Abstract #8075)

About Millennium

Millennium: the Takeda Oncology Company, a leading biopharmaceutical company based in Cambridge, Mass., markets VELCADE, a first-in-class proteasome inhibitor, and has a robust clinical development pipeline of product candidates. Millennium Pharmaceuticals, inc. was acquired by Takeda Pharmaceutical Company Ltd. in may, 2008. the Company’s research, development and commercialization activities are focused in oncology. Additional information about Millennium is available through its website, millennium.com.

About Takeda

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, takeda.com.

About VELCADE

VELCADE is co-developed by Millennium and Ortho Biotech Oncology Research & Development, unit of Johnson & Johnson Pharmaceutical Research & Development, L.L.C. 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 more than 90 countries and has been used to treat more than 230,000 patients worldwide.

Indications and important Safety Information (Patient)

What is VELCADE® (bortezomib) used for?

VELCADE is approved for the treatment of patients with multiple myeloma (a cancer of the plasma cells). VELCADE is also approved for the treatment of patients with mantle cell lymphoma (a cancer of lymph nodes) who have already received other treatments.

How is VELCADE administered?

VELCADE is prescribed by a physician experienced in the use of medications to treat cancer. it is administered as an injection into your vein (IV) by a health care professional.

Who Should not Receive VELCADE?

Before you receive treatment with VELCADE, tell your doctor about all of your medical conditions. you should not receive VELCADE if you are:

• allergic to bortezomib, boron or mannitol
• pregnant or plan to become pregnant
• breastfeeding. Discuss with your doctor when it is safe to restart breastfeeding after finishing your treatment.

the effects of VELCADE in children have not been evaluated.

What are the Possible Side Effects of VELCADE?

VELCADE can cause serious side effects including:

• Neutropenia (low levels of neutrophils, a type of white blood cell) and Thrombocytopenia (low levels of platelets). VELCADE can cause low levels of white blood cells (infection fighting cells) and/or platelets (clot-forming cells). you will have regular blood tests to check your cell counts during your treatment with VELCADE. if the number of these cells is very low, your doctor may change the dose and/or schedule of VELCADE. if your white blood cells become low, you can be at higher risk for infections. tell your doctor if you develop a fever or believe you have an infection. if platelets become very low, there is an increased risk of bleeding. Your doctor may recommend a platelet transfusion. There have been cases of bleeding in the stomach, bowels and brain during treatment with VELCADE.
• Gastrointestinal Problems. VELCADE treatment can cause nausea, vomiting, diarrhea, and constipation. if your symptoms are severe, your doctor may recommend IV fluids and/or medications.
• Peripheral neuropathy. VELCADE can cause damage to the nerves, a condition called peripheral neuropathy. you may feel muscle weakness, tingling, burning, pain, and loss of feeling in your hands and feet, any of which can be severe. tell your doctor if you notice any of these symptoms. Your doctor may change the dose and/or schedule of VELCADE or stop it altogether.
• Low blood pressure. VELCADE can cause a drop in blood pressure. tell your doctor if you have low blood pressure, feel dizzy or feel as though you might faint. if you are taking drugs that lower blood pressure, your medications might need to be adjusted. if you are not drinking enough liquids, your doctor may need to administer IV fluids.

• Heart problems. VELCADE treatment can cause or worsen heart rhythm problems and heart failure. Your doctor may closely monitor you if you have, or are at risk for, heart disease. tell your doctor if you experience chest pressure or pain, palpitations, swelling of your ankles or feet, or shortness of breath.
• Lung Disorders. There have been reports of lung disorders in patients receiving VELCADE. Some of these events have been fatal. tell your doctor if you experience any cough, shortness of breath, wheezing or difficulty breathing.
• Liver disease. if you have liver problems, it can be harder for your body to get rid of VELCADE. VELCADE has caused sudden liver failure in patients who were taking many medications or had other serious medical conditions. Symptoms of liver problems include a yellow discoloration of the eyes and skin (jaundice) and changes in liver enzymes measured in blood tests. Your doctor will closely monitor you if you have liver disease. in patients with moderate or severe liver disease, VELCADE should be started at a lower dose. Additional dose adjustments may be made based on your tolerance of the drug.
• Tumor Lysis Syndrome (TLS). TLS can occur with cancer treatments and your doctor will be monitoring blood and urine for any signs of this syndrome. if you develop TLS, your doctor will take appropriate steps to treat it.
• Reversible Posterior Leukoencephalopathy Syndrome (RPLS). There have been reports of a rare, reversible condition involving the brain called RPLS in patients treated with VELCADE. Patients with RPLS can have seizures, high blood pressure, headaches, tiredness, confusion, blindness or other vision problems. VELCADE treatment should be stopped in cases of RPLS.

the most common side effects seen in patients receiving VELCADE include: thrombocytopenia, neutropenia, nausea, peripheral neuropathy, neuralgia (nerve pain), pyrexia (high temperature), diarrhea, anemia, leukopenia (low levels of white blood cells), decreased appetite, fatigue, constipation, vomiting, dehydration, dyspnea (difficulty breathing), cough, asthenia (low energy), insomnia (trouble sleeping), peripheral edema (swelling of the limbs), and headache.

What other information should you discuss with your doctor?

you should also tell your doctor if you:

• have kidney disease. if you are on dialysis, your doctor will administer VELCADE after the dialysis procedure.
• are taking medication for diabetes. VELCADE can affect your blood glucose levels. Your doctor may require close monitoring of your blood glucose levels and change the dose of your diabetes medicine while you are being treated with VELCADE.
• have liver disease.
• are using medicines like ketoconazole (an anti-fungal) and ritonavir (an anti-viral), which will require close monitoring during treatment with VELCADE.
• are using any other medications (including over the counter drugs), herbal or dietary supplements, or holistic treatments.
• develop a rash of any type while receiving VELCADE.

the side effects of VELCADE may impair your ability to drive or operate machinery.

These are not all of the possible side effects with VELCADE. it is important to always contact your doctor if you experience any side effects while on VELCADE. if you have any questions about VELCADE, contact your doctor. Additional information and full prescribing information is available at VELCADE.com.

Please see the full prescribing information for VELCADE including warnings and precautions.

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).

Editors’ Note: this press release is also available under the Media section of the Company’s website at: millennium.com/InTheNews.aspx.