Cambridge, MA (Press Release) – 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 the retreatment of adult patients with multiple myeloma (MM) who had pre­vi­ously responded to VELCADE ther­apy and re­lapsed at least six months fol­low­ing completion of prior VELCADE treat­ment. The labeling update in­cludes dosing guidelines as well as safety and efficacy findings for the use of VELCADE as a single agent or VELCADE in com­bi­na­tion with dexa­meth­a­sone in patients pre­vi­ously treated with VELCADE. VELCADE retreatment may be started at the last tolerated dose.

The approved retreatment sNDA consisted of a Phase 2 study and other sup­port­ive data. The Phase 2 inter­na­tional RETRIEVE trial showed a 38.5 per­cent over­all response rate (ORR) in multiple myeloma patients who had been pre­vi­ously treated with a VELCADE-based regi­men (median of two prior lines of ther­apy) and had pre­vi­ously achieved a partial response or better. The safety profile seen with VELCADE retreatment was con­sis­tent with the known safety profile of in­tra­venous VELCADE in re­lapsed multiple myeloma; no cumulative toxicities were observed upon retreatment. The most common adverse drug reac­tion was thrombo­cytopenia, which occurred in 52 per­cent of the patients.

"For the past 11 years, VELCADE has played an important role as the only ther­apy proven to extend over­all survival for patients with newly diag­nosed and re­lapsed multiple myeloma,” said Michael Vasconcelles, MD, Global Head, Oncology Therapeutic Area Unit, Takeda. “With these newly approved dosing guidelines, physicians will be able to provide their patients, who have pre­vi­ously received VELCADE, with an effective treat­ment extending VELCADE use across the con­tin­uum of care of multiple myeloma."

RETRIEVE was a single arm, open-label trial. The study enrolled 130 patients ages 18 years and older who had pre­vi­ously responded to VELCADE-based ther­apy and re­lapsed at least six months after prior treat­ment with VELCADE. The study met its pri­mary end­point of best con­firmed response to retreatment as assessed by European Group for Blood and Marrow Transplantation (EBMT) criteria.

• Patients had received a median of two prior therapies (range of 1-7).
• Dexamethasone was administered in combination with VELCADE in 94 patients.
• Of the 130 patients, one patient achieved complete response and 49 achieved partial response (50/130; ORR 38.5 percent).
• In the 50 responding patients, the median duration of response was 6.5 months (range of 0.6 to 19.3 months).
• The incidence of grade >3 thrombocytopenia was 24 percent. Peripheral neuropathy occurred in 28 percent of patients, with the incidence of grade >3 peripheral neuropathy reported at 6 percent. The incidence of serious adverse reactions was 12.3 percent; the most commonly reported serious ad­verse reactions were thrombocytopenia (3.8 percent), diarrhea (2.3 percent), herpes zoster and pneu­mo­nia (1.5 percent each). Adverse reactions leading to discontinuation occurred in 13 percent of pa­tients.

VELCADE: 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 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.

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 for a com­plete list avail­able at VELCADE.com.

About VELCADE®

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 more than 90 countries and has been used to treat more than 550,000 patients world­wide.

About Millennium: The Takeda Oncology Company

Millennium: The Takeda Oncology Company, a leading bio­pharma­ceu­tical com­pany 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, http://www.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, http://www.takeda.com/.

Source: Millennium.