Amgen announced that a Phase III trial met its main goal, with results demonstrating that patients with relapsed multiple myeloma treated with Kyprolis (carfilzomib) lived twice as long without their disease worsening compared to Johnson & Johnson and Takeda's Velcade (bortezomib). "We are excited about the results...and the potential positive impact for patients with relapsed multiple myeloma," remarked Amgen CEO Robert A. Bradway.
The ENDEAVOR study randomised 929 patients whose multiple myeloma had relapsed after at least one, but not more than three prior therapeutic regimens, to receive Kyprolis or Velcade, both in combination with low-dose dexamethasone. Amgen noted that an interim analysis showed that median progression-free survival for patients given Kyprolis was 18.7 months, versus 9.4 months for those who received Velcade.
In addition, the company said that Kyprolis demonstrated "superiority" over Velcade for secondary objectives of higher overall response rate and lower neuropathy events. Overall survival data are not yet mature, and Sean Harper, Amgen's head of R&D, said the study will continue until overall survival can be determined. "This was the bet we made when we acquired. Onyx [Pharmaceuticals]," Harper said, "to be able to demonstrate something compelling enough with respect to the difference between Kyprolis and Velcade," which will lose US patent protection in 2017.
According to Amgen, treatment discontinuation due to adverse events and on-study deaths were comparable between Kyprolis and Velcade. The drugmaker indicated that rates of cardiac failure and renal failure for Kyprolis were comparable to those seen in the Phase III ASPIRE study. Amgen added that in the ENDEAVOR trial, the rates for cardiac and renal failure were higher in the Kyprolis arm versus the Velcade arm, while there was an increase in the incidence of hypertension and dyspnoea in the Kyprolis arm compared to Velcade and that observed in the ASPIRE study. Full data will be submitted for presentation at the American Society of Clinical Oncology annual meeting.
Kyprolis was granted accelerated approval in 2012 by the FDA for the treatment of patients with multiple myeloma who have received at least two prior therapies including Velcade and an immunomodulatory agent and have demonstrated disease progression on or within 60 days of completion of the last therapy. The drug, which is also authorised in Argentina, Mexico and Israel, generated sales last year of $331 million.
Earlier this year, Amgen filed for FDA approval of Kyprolis as a second-line treatment for patients with multiple myeloma based on positive data from the ASPIRE trial. Harper noted that results from the head-to-head CLARION trial comparing Kyprolis to Velcade in newly diagnosed multiple myeloma patients are expected in 2016. Although Takeda has announced positive results from a trial for an oral version of Velcade, Harper suggested that such oral proteasome inhibitors will likely be used as "maintenance" treatments for multiple myeloma patients whose disease is first controlled by existing drugs given by infusion.
For related analysis, see ViewPoints: With generic Velcade on the horizon, Amgen delivers a timely boost to Kyprolis profile.
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