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.