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.