Amgen Seeks Expanded Approval of Kyprolis to Once-weekly Regimen for Relapsed Myeloma

Amgen is seeking to expand the approval of its proteasome inhibitor Kyprolis (carfilzomib) in the U.S. to include once-weekly dosing combined with dexamethasone for multiple myeloma patients with hard-to-treat disease or whose disease relapsed.

The company used data from its Phase 3 ARROW trial as the basis for its supplemental new drug application (sNDA) to the U.S. Food and Drug Administration.

The ARROW trial (NCT02412878) recruited 478 patients with relapsed or hard to treat multiple myeloma who had already received two or three lines of therapy, including the proteasome inhibitor Velcade (bortezomib) and an immunomodulatory agent (IMiD) — a drug that works by adjusting immune responses in inflammatory diseases and malignancies.

Proteasome inhibitors like Kyprolis allow the buildup of faulty proteins inside cells, triggering their death. This is especially true in myeloma cells because they are more likely to contain a higher amount of abnormal proteins.

During the clinical trial, patients were randomized to receive a once-weekly, 30-minute infusion of Kyprolis (20 mg/m² on day 1, and thereafter 70 mg/m²) plus dexamethasone (40 mg), or a 10-minute infusion twice-weekly (20 mg/m² on day 1, and thereafter 27 mg/m²), also with dexamethasone.

The trial’s main goal was to determine the time to disease worsening or death. Secondary endpoints included overall response rate, overall survival, and safety, along with several other parameters.

The results showed that patients treated with once-weekly Kyprolis lived significantly longer without disease progression than those receiving the twice-weekly regimen (11.2 months vs. 7.6 months, respectively) — a 31% difference.

Also, the overall response rate was higher in the once-weekly group compared to those treated with the twice-weekly regimen, 62.9% vs. 40.8%, respectively.

Complete responses were reached by 7.1% of patients in the once-weekly arm vs. 1.7% in the twice-weekly arm.

The results of the trial were published in the journal The Lancet Oncology in a study titled, “Once weekly versus twice weekly carfilzomib dosing in patients with relapsed and refractory multiple myeloma (A.R.R.O.W.): interim analysis results of a randomised, phase 3 study.”

Amgen also presented the trial’s results at the 54th Annual Meeting of the American Society of Clinical Oncology.

“I’m proud of our continued dedication to the Kyprolis clinical program, with a focus on generating additional data to reduce the dosing and administration burden on patients with relapsed or refractory multiple myeloma,” David M. Reese, MD, executive vice president of research and development at Amgen, said in a press release.

“Data from the Phase 3 A.R.R.O.W. study illustrates Kyprolis’ potential to extend the time patients live without their disease progressing while also providing a more convenient once-weekly dosing option for this frequently relapsing and difficult-to-treat cancer. We look forward to working with the Agency to bring this more streamlined dosing regimen to patients,” he added.

The FDA is reviewing Amgen’s sNDA under the Oncology Center of Excellence Real-Time Oncology Review and Assessment Aid pilot programs, which are exploring a more efficient review process so that treatments found effective and safe can reach patients promptly without delays.

Kyprolis is currently approved in the U.S., alone and in combination with Celgene’s Revlimid (another proteasome inhibitor) plus dexamethasone or dexamethasone only, as a twice-weekly treatment for myeloma patients who failed prior treatment regimens.