Amgen announces submission of supplemental New Drug Application to FDA for Kyprolis (carfilzomib)

Amgen (NASDAQ: AMGN) today announced the submission of a supplemental New Drug Application (sNDA) to the U.S. Food and Drug Administration (FDA) for Kyprolis® (carfilzomib) for Injection to seek an expanded indication for the treatment of patients with a form of blood cancer, relapsed multiple myeloma, who have received at least one prior therapy. Kyprolis currently has accelerated approval in the U.S. for the treatment of patients with relapsed multiple myeloma as a monotherapy.

The sNDA is based on data from the global Phase 3 ENDEAVOR trial. The ENDEAVOR study is the first of two head-to-head Phase 3 trials of Kyprolis versus Velcade® (bortezomib). Relapsed multiple myeloma patients treated with Kyprolis and dexamethasone in the ENDEAVOR study lived twice as long without their disease worsening, demonstrating statistically and clinically significant superiority over Velcade (median progression-free survival [PFS] 18.7 months versus 9.4 months, HR=0.53, 95 percent CI, 0.44 – 0.65; p<0.0001).

"Submission of this new sNDA for Kyprolis is important because if approved, it will mean more treatment options for patients with this serious disease. Multiple myeloma has historically been one of the most difficult to treat diseases because of the inherent complexities related to the recurring pattern of remission and relapse," said Sean E. Harper, M.D., executive vice president of Research and Development at Amgen. "The ENDEAVOR study showed that patients who had failed at least one prior therapy were half as likely to see their disease worsen if they received Kyprolis. This is yet another data set that illustrates Kyprolis' potential to extend the time patients live without their disease progressing and improve the depth and duration of a response."

The Kyprolis combination demonstrated superiority over the Velcade combination for secondary objectives of higher overall response rate and lower neuropathy events. Overall survival data are not yet mature and continue to be monitored.

Treatment discontinuation due to adverse events and on-study deaths was comparable between the two arms. The rates of cardiac failure and renal failure for Kyprolis were comparable to those observed in the Phase 3 ASPIRE study. In ENDEAVOR, the rates for cardiac and renal failure were higher in the Kyprolis arm versus the Velcade arm. There was also an increase in the incidence of hypertension and dyspnea in the Kyprolis arm compared to Velcade in ENDEAVOR and than that observed in the ASPIRE study.

Based on the Phase 3 ASPIRE study Amgen continues to work with the FDA on the related sNDA in the U.S. and with the European Union (EU) regulatory authorities for the Marketing Authorization Application for Kyprolis. Following potential approval based on the ASPIRE study, Amgen plans to submit ENDEAVOR for potential authorization in the EU.

Kyprolis Head-to-Head Studies
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 dexamethasone, versus Velcade with dexamethasone in patients whose multiple myeloma has relapsed after at least one, but not more than three prior therapeutic regimens. The primary endpoint of the trial was PFS, defined as the time from treatment initiation to disease progression or death.

Patients received Kyprolis as a 30-minute infusion along with dexamethasone (20 mg). Administer Kyprolis at a starting dose of 20 mg/m2 in Cycle 1 on Days 1 and 2. If tolerated, escalate the dose to a target dose of 56 mg/m2 on Day 8 of Cycle 1. Patients were kept at 56 mg/m2 on days 9, 15 and 16 on a 28 day cycle. Patients who tolerated 56 mg/m2 in Cycle 1 were kept at this dose for subsequent cycles on days 1, 2, 8, 9, 15 and 16 on a 28 day cycle. Patients who received Velcade (1.3 mg/m2) with dexamethasone (20 mg) were administered Velcade subcutaneously or intravenously at the discretion of the investigator and in accordance with 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.

Kyprolis is also being evaluated in the CLARION study, a head-to-head Phase 3 multicenter, open-label, randomized study in transplant-ineligible patients with newly diagnosed multiple myeloma. The study is evaluating the safety and efficacy of carfilzomib, melphalan and prednisone versus bortezomib, melphalan and prednisone.

Source:

Amgen

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