Amgen announced that the U.S. Food and Drug Administration (FDA) has approved the supplemental New Drug Application (sNDA) to add overall survival (OS) data from the Phase 3 head-to-head ENDEAVOR trial to the Prescribing Information for KYPROLIS(carfilzomib). Data added to the label demonstrated that KYPROLIS and dexamethasone (Kd) reduced the risk of death by 21 percent and increased OS by 7.6 months versus Velcade (bortezomib) and dexamethasone (Vd) in patients with relapsed or refractory multiple myeloma (median OS 47.6 months for Kd versus 40.0 months for Vd, HR=0.79; p=0.01).
“Overall survival is generally considered to be the gold standard of endpoints because it clearly demonstrates a drug’s value in extending a patient’s life,” said David M. Reese, M.D., senior vice president of Translational Sciences and Oncology at Amgen. “Blood cancer therapies approved by the FDA between 2003 and 2013 only improved overall survival by an average of 2.61 months. KYPROLIS and dexamethasone improved overall survival by 7.6 months, underscoring that this regimen is a significant advancement and should be considered a standard of care for patients with relapsed or refractory multiple myeloma.”
The National Comprehensive Cancer Network Clinical Practice Guidelines in Oncology (NCCN Guidelines) list Kd as the only preferred doublet regimen at relapse for multiple myeloma. Full OS results from the ENDEAVOR trial were published earlier this year in The Lancet Oncology.
Adverse events observed in this updated analysis were consistent with those previously reported for ENDEAVOR. The most common adverse events (greater than or equal to 20 percent) in the KYPROLIS arm were anemia, diarrhea, pyrexia, dyspnea, fatigue, hypertension, cough, insomnia, upper respiratory tract infection, peripheral edema, nausea, bronchitis, asthenia, back pain, thrombocytopenia and headache.
Since its approval in 2012, more than 50,000 patients worldwide have received KYPROLIS. The KYPROLIS clinical program continues to focus on providing treatment options for physicians and patients for this frequently relapsing and difficult-to-treat cancer. KYPROLIS is available for patients whose myeloma has relapsed or become resistant to another treatment and continues to be studied in a range of combinations and patient populations.
The randomized ENDEAVOR (RandomizEd, OpeN Label, Phase 3 Study of Carfilzomib Plus DExamethAsone Vs Bortezomib Plus DexamethasOne in Patients With Relapsed Multiple Myeloma) trial of 929 patients evaluated KYPROLIS in combination with low-dose dexamethasone, versus Velcade with low-dose dexamethasone in relapsed or refractory patients who previously received at least one, but not more than three, prior therapeutic regimens. The primary endpoint of the trial was progression-free survival, defined as the time from treatment initiation to disease progression or death. The primary analysis was published in The Lancet Oncology and is described in the Prescribing Information.
Patients received treatment until progression with KYPROLIS as a 30-minute infusion on days 1, 2, 8, 9, 15 and 16 of 28 day treatment cycles, along with low-dose dexamethasone (20 mg). For cycle one only, KYPROLIS was administered at 20 mg/m2 on days 1 and 2, and if tolerated was escalated to 56 mg/m2 from day 8 of cycle one onwards. Patients who received Velcade (1.3 mg/m2) with low-dose dexamethasone (20 mg) were treated with Velcade administered subcutaneously or intravenously at the discretion of the investigator and in accordance with regional regulatory approval of Velcade. More than 75 percent of the patients in the control arm received Velcade subcutaneously. This study was conducted at 235 sites worldwide.
Filed Under: Drug Discovery