Amgen’s Kyprolis fails to outperform Velcade in first-line multiple myeloma PhIII

Amgen’s ($AMGN) Kyprolis has come up short against Takeda’s Velcade in a Phase III trial in patients newly diagnosed with multiple myeloma. The data undermine Amgen’s attempts to justify the $10.4 billion it paid for Onyx Pharmaceuticals by establishing Kyprolis as a cornerstone of first-line multiple myeloma treatment.

For the Phase III trial, Amgen enrolled 995 patients and randomized them to receive one of two regimens, which paired either Kyprolis or Velcade with melphalan and prednisone. After 54 weeks, there was next to nothing between the two cohorts in terms of progression-free survival, resulting in the trial missing its primary endpoint. Median PFS in the Kyprolis arm was 22.3 months, compared to 22.1 months for the Velcade cohort.

"The Clarion results … are disappointing, especially given the robust data we've seen in the second-line setting,” Sean Harper, head of R&D at Amgen, said in a statement.

Second-line data posted last year associated a Kyprolis-based regimen with a PFS of 18.7 months, compared to 9.4 months for the Velcade cohort, an outcome that prompted Harper to tell Forbes the Amgen drug “really looks like it’s got quite a bit more oomph to it.”

The first-line results tell a different story, leaving Amgen without the data to argue for the use of Kyprolis over Velcade in a first-line setting, an indication that would help it to grow sales past the $512 million it achieved last year and toward the sorts of blockbuster numbers analysts discussed at the time of the Onyx acquisition.

Since Amgen bought Onyx, new drugs from AbbVie ($ABBV), Bristol-Myers Squibb ($BMY), and Johnson & Johnson ($JNJ) have crowded into the multiple myeloma space. But with Kyprolis seemingly on track to outperform Velcade prior to the first-line readout, Amgen had hoped its drug would become the foundation for all multiple myeloma treatment regimens.

Speaking in July, Amgen CEO Robert Bradway said: “We expect [Kyprolis] to be a backbone of multiple myeloma therapy for the foreseeable future, and as such, for it to be used in combination with many of the new agents that are emerging in the field.”

With the first-line trial failing to deliver data to support the use of Kyprolis over Velcade, that hypothesis appears shakier than it did at the time. Amgen is now left looking to a Phase III trial in which newly diagnosed multiple myeloma patients are receiving either Kyprolis or Velcade plus Celgene’s ($CELG) Revlimid and dexamethasone to revitalize the prospects of its product.