Approval

Amgen Gets US FDA Approval For Kyprolis In Combo With Darzalex Faspro And Dexamethasone For Patients With Multiple Myeloma At First Or Subsequent Rela

December 06,2021 11:14 AM
- By Admin

Amgen announced that the US Food and Drug Administration (FDA) has approved the expansion of the Kyprolis (carfilzomib) US prescribing information to include its use in combination with Darzalex Faspro (daratumumab and hyaluronidase-fihj) and dexamethasone for the treatment of adult patients with relapsed or refractory multiple myeloma who have received one to three lines of therapy.  

"I am pleased that the addition of subcutaneous daratumumab to Kyprolis plus dexamethasone will offer increased flexibility and convenience for patients with relapsed or refractory multiple myeloma and will greatly reduce the administration burden," said David M. Reese, M.D., executive vice president of research and development at Amgen.

The expansion of the Kyprolis prescribing information to include Darzalex Faspro plus dexamethasone was supported by the ongoing, phase 2, non-randomized, open-label, multicenter Pleiades trial evaluating the clinical benefit of Darzalex Faspro administered in combination with four standard-of-care treatment regimens in patients with multiple myeloma.

Updated data from the PLEIADES study were presented at the 2020 American Society of Hematology (ASH) Annual Meeting, demonstrating that response rates with Kyprolis in combination with Darzalex Faspro and dexamethasone were similar to those in the phase 3 CANDOR study (Kyprolis combined with intravenous [IV] Darzalex and dexamethasone [DKd]), which supported the first-ever approval of an anti-CD38 monoclonal antibody in combination with Kyprolis. The PLEIADES study met its primary endpoint, demonstrating an overall response rate of 84.8 per cent with Darzalex Faspro-Kd.

"Managing and coping with relapsed disease is a particularly challenging time in a patient's treatment journey, and having the option of subcutaneous daratumumab as part of the DKd treatment regimen will be a welcomed option for many of our patients," said Dr. Saad Usmani, M.D., chief of Myeloma Service at Memorial Sloan Kettering Cancer Center. "Administration time can be drastically reduced, as compared to the intravenous daratumumab formulation in combination with carfilzomib and dexamethasone."

Serious adverse reactions occurred in 27% of patients who received Kyprolis in combination with Darzalex Faspro and dexamethasone. The most common adverse reactions (=20%) were upper respiratory tract infection, fatigue, insomnia, hypertension, diarrhea, cough, dyspnea, headache, pyrexia, nausea and peripheral edema. Fatal adverse reactions occurred in 3% of patients.

Amgen will be submitting marketing applications globally.

Darzalex Faspro and Darzalex are registered trademarks of Johnson & Johnson.

The ongoing, phase 2, non-randomized, open-label, multicenter PLEIADES trial evaluated the clinical benefit of Darzalex Faspro administered in combination with four standard-of-care treatment regimens in patients with multiple myeloma. The efficacy of KYPROLIS in combination with Darzalex Faspro and dexamethasone was evaluated in 66 patients with relapsed or refractory multiple myeloma in a single-arm cohort of PLEIADES.

Kyprolis was evaluated at a starting dose of 20 mg/m2 on Cycle 1 Day 1, which was increased to 70 mg/m2 as a 30-minute IV infusion on Cycle 1 Day 8 and Day 15, and then Day 1, 8 and 15 of each cycle; Darzalex Faspro 1,800 mg administered subcutaneously once weekly from Weeks 1 to 8, once every 2 weeks from Weeks 9 to 24 and once every 4 weeks starting with Week 25 until disease progression or unacceptable toxicity; and dexamethasone 40 mg per week.

CANDOR, a randomized, open-label Phase 3 study of Kyprolis, Darzalex (IV) and dexamethasone (DKd) compared to Kyprolis and dexamethasone (Kd), has evaluated 466 relapsed or refractory multiple myeloma patients who have received one to three prior therapies. Patients were treated until disease progression. The primary endpoint was progression-free survival (PFS), and the key secondary endpoints were overall response rate, minimal residual disease and overall survival. PFS was defined as time from randomization until disease progression or death from any cause.

In the first arm, patients received Kyprolis twice weekly at 56 mg/m2 and dexamethasone in combination with Darzalex. In the second arm (control), patients received Kyprolis twice weekly at 56 mg/m2 and dexamethasone.

CANDOR was initiated as part of a collaboration with Janssen, and under the terms of the agreement, Janssen co-funded the study.

Multiple myeloma is an incurable blood cancer, characterized by a recurring pattern of remission and relapse. It is a rare and life-threatening disease that accounts for approximately one per cent of all cancers.  Worldwide, approximately 176,000 people are diagnosed with multiple myeloma each year, and 117,000 patient deaths are reported on an annual basis.

Proteasomes play an important role in cell function and growth by breaking down proteins that are damaged or no longer needed. Kyprolis has been shown to block proteasomes, leading to an excessive build-up of proteins within cells.5 In some cells, Kyprolis can cause cell death, especially in myeloma cells because they are more likely to contain a higher amount of abnormal proteins.