Date: 2013-11-20
Type of information: Granting of a Market Authorisation in the EU
Product name: Kadcyla®
Compound: trastuzumab emtansine (T-DM1)
Therapeutic area: Cancer - Oncology
Action mechanism: antibody drug conjugate. Kadcyla® is an antibody drug conjugate (ADC). Because a stable linker is used, the ADC largely remains intact outside the cancer cell, with the cytotoxic agent in an inactive state until it enters the cancer cell, thereby minimising exposure of normal cells to the chemotherapy. The humanized monoclonal antibody (trastuzumab) binds to the HER2-positive cancer cells, and is thought to block out of control signals that contribute to cancer growth and survival while also calling on the body’s immune system to attack the cells. After binding, trastuzumab emtansine (T-DM1) is internalized into those cancer cells, DM1 containing metabolites of the conjugate specifically destroy the cells. Roche licenses technology for Kadcyla under an agreement with ImmunoGen.
Company: Genentech (USA), a member of Roche Group (Switzerland)
Disease: people with HER2-positive, unresectable locally advanced or metastatic breast cancer (mBC) who have received prior treatment with Herceptin® (trastuzumab) and a taxane chemotherapy
Latest news: * On February 22, 2013, the FDA has approved Roche’s Kadcyla® (trastuzumab emtansine), the first antibody-drug conjugate for the treatment of people with HER2-positive metastatic breast cancer (mBC) who have received prior treatment with Herceptin® (trastuzumab) and a taxane chemotherapy. Kadcyla® is the fourth medicine from Roche to receive FDA approval for people with advanced cancers within the past two years. * On November 20, 2013, Roche has announced that Kadcyla® (trastuzumab emtansine or T-DM1), the latest targeted medicine from its HER2 franchise and its first antibody-drug conjugate, has been approved by the European Commission for people with previously treated HER2-positive advanced breast cancer.Specifically, Kadcyla® is indicated as a single agent for the treatment of adults with HER2-positive, unresectable locally advanced or metastatic breast cancer who previously received Herceptin® (trastuzumab) and a taxane, separately or in combination. The indication also stipulates that those treated should either have received prior therapy for locally advanced or metastatic disease, or have had disease recurrence during or within six months of completing adjuvant therapy.* On September 20, 2013, Roche has announced that the European Union’s (EU) Committee for Medicinal Products for Human Use (CHMP) has recommended approval of Kadcyla® (trastuzumab emtansine or T-DM1) as a single agent, for the treatment of adult patients with HER2-positive, unresectable locally advanced or metastatic breast cancer who previously received trastuzumab and a taxane, separately or in combination.The CHMP opinion is based on clinical data from the international, Phase III EMILIA study which found that Kadcyla® helped people with HER2-positive locally advanced or metastatic breast cancer who had previously been treated with Herceptin and a taxane chemotherapy to live for nearly 10 months (9.6 months) without their disease getting worse and extended their life expectancy to more than two and a half years overall (30.9 months). Kadcyla® has also demonstrated a tolerable safety profile and is associated with fewer of the severe side effects usually experienced with current chemotherapy known to impact patients’ daily lives.The EU filing of Kadcyla is based on results from EMILIA (TDM4370g/BO21977), an international, Phase III, randomised, open-label study comparing Kadcyla alone to lapatinib in combination with Xeloda in 991 patients with HER2-positive locally advanced breast cancer or mBC who had previously been treated with Herceptin and a taxane chemotherapy.The most common side effects with trastuzumab emtansine are haemorrhage (including epistaxis), increased transaminases, fatigue, musculoskeletal pain, and headache. A pharmacovigilance plan for Kadcyla® will be implemented as part of the marketing authorisation.Kadcyla® should be prescribed by physicians experienced in the treatment of cancer patients. Patients treated with trastuzumab emtansine should have HER2 positive tumour status, defined as a score of 3 + by immunohistochemistry (IHC) or a ratio of ? 2.0 by in situ hybridization (ISH) assessed by a CEmarked In Vitro Diagnostic (IVD) medical device. If a CE-marked IVD is not available, the HER2-status should be assessed by an alternate validated test.In order to prevent medication errors it is important to check the vial labels to ensure that the medicinal product being prepared and administered is Kadcyla® (trastuzumab emtansine) and not Herceptin® (trastuzumab).
Kadcyla® will be available to people in the United States within two weeks. As part of this approval, Genentech plans to initiate patient assistance programs for people taking Kadcyla® through Genentech Access Solutions.
The FDA approval of Kadcyla® is based on results from EMILIA (TDM4370g/BO21977), an international, Phase III, randomized, open-label study comparing Kadcyla alone to lapatinib in combination with Xeloda® (capecitabine) in 991 people with HER2-positive locally advanced breast cancer or mBC who had previously been treated with Herceptin and a taxane chemotherapy. People who received Kadcyla® lived a median of 5.8 months longer (overall survival) than those who received the combination of lapatinib and Xeloda®, the standard of care in this setting (median overall survival: 30.9 months vs. 25.1 months).
People receiving Kadcyla® experienced a 32 percent reduction in the risk of dying compared to people who received lapatinib and Xeloda® (HR=0.68; p=0.0006).
No new safety signals were observed and adverse events (AEs) were consistent with those seen in previous studies, with fewer people who received Kadcyla® experiencing Grade 3 or higher (severe) AEs than those who received lapatinib plus Xeloda® (43.1 percent vs. 59.2 percent).
For people receiving Kadcyla®, the most common (occurring in more than 2 percent of participants) Grade 3 or higher AEs were low platelet count (14.5 percent), increased levels of enzymes released by the liver and other organs (8.0 percent), low red blood cell count (4.1 percent), low levels of potassium in the blood (2.7 percent), nerve problems (2.2 percent) and tiredness (2.5 percent).
* On November 6 2012, Genentech, a member of the Roche Group has announced that the FDA has accepted the compan's Biologics License Application (BLA) for trastuzumab emtansine (T-DM1) and granted Priority Review. Trastuzumab emtansine’s proposed indication is for the treatment of people with HER2-positive, unresectable locally advanced or metastatic breast cancer (mBC) who have received prior treatment with Herceptin® (trastuzumab) and a taxane chemotherapy. The FDA confirmed the action date is February 26, 2013.
Roche’s Marketing Authorization Application for trastuzumab emtansine for people with HER2-positive mBC has also been accepted for review by the European Medicines Agency (EMA).
Patents:
Submission of marketing authorization application USA :
Submission of marketing authorization application UE:
Withdrawal of marketing authorization application USA:
Withdrawal of marketing authorization application UE:
US authorization: 2013-02-22
UE authorization: 2013-11-20
Favourable opinion UE: 2013-09-19
Favourable opinion USA:
Orphan status USA:
Orphan status UE:
Pediatric exclusivit _USA:
Pediatric exclusivity UE: OTC status: Other news:
