FDA批准武田万珂（Velcade）用于多发性骨髓瘤（MM）复治

武田（Takeda）及旗下千禧制药（Millennium）8月9日宣布，FDA已批准Velcade（万珂，通用名：硼替佐米，bortezomib）用于曾对万珂治疗有响应且完成最后一次万珂治疗后至少6个月后病情复发的多发性骨髓瘤（multiple myeloma，MM）成人患者的复治（retreatment，即再治疗）。Velcade的产品标签更新包括给药指南以及Velcade作为单药或Velcade联合地塞米松用于Velcade经治患者复治时的安全性和疗效数据。Velcade复治可以根据最后一次治疗的耐受剂量开始。

此前，Velcade已获批用于多发性骨髓瘤（MM）的治疗，以及用于既往接受过至少一种疗法的套细胞淋巴瘤（MCL）的治疗。

FDA批准Velcade用于复治的补充新药申请（sNDA），包括一项II期研究及其他支持数据。该II期国际性RETRIEVE研究表明，既往接受过Velcade治疗且经Velcade治疗取得部分缓解或完全缓解的多发性骨髓瘤（MM）患者群体，接受Velcade复治时的总缓解率（ORR）为38.5%。研究中，Velcade复治的安全性与已知的静脉注射Velcade治疗复发性多发性骨髓瘤（MM）的安全性一致。研究中最常见的药物不良反应为血小板减少，约发生于52%的患者中。

在过去的11年里，Velcade作为唯一一种已被证明能够延缓新诊（newly diagnosed）或复发性多发性骨髓瘤（MM）患者总生存期（OS）的药物，在多发性骨髓瘤（MM）的临床治疗中发挥了重要作用。Velcade新获批的给药指南，将使医生能够为其Velcade经治患者继续提供这种有效的药物治疗，将Velcade用于多发性骨髓瘤的整个临床护理范畴。

关于万珂（Velcade）：

Velcade由武田与强生联合开发，武田负责该药在美国的商业化，强生则负责药物在欧洲及世界其他地区的商业化，在日本，武田和强生联合推广该药。目前，Velcade已获全球90多个国家批准，经该药治疗的全球患者总数超过55万。

英文原文：FDA Approves VELCADE® (bortezomib) Retreatment in Patients with Multiple Myeloma

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). TLS is 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.