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FDA Grants Priority Review for Kyprolis (Carfilzomib) for Treatment of Relapsed Multiple Myeloma

Approval decision expected in July

The FDA has accepted a supplemental new drug application (sNDA) for Kyprolis (carfilzomib, Onyx Pharmaceuticals/Amgen) injection for the treatment of patients with relapsed multiple myeloma who have received at least one prior therapy.

The sNDA is designed to support the conversion of accelerated approval to full approval and to expand the current Kyprolis indication. As part of the acceptance, the FDA granted Kyprolis priority review, with a Prescription Drug User Fee Act (PDUFA) target action date of July 26, 2015.

Priority review is assigned to applications for drugs that treat serious conditions that and would, if approved, provide significant improvements in the safety or effectiveness of the treatment, diagnosis, or prevention of serious conditions.

The sNDA was based on data from the phase III ASPIRE (CArfilzomib, Lenalidomide, and DexamethaSone Versus Lenalidomide and Dexamethasone for the Treatment of PatIents With Relapsed Multiple MyEloma) trial and on other relevant data.

The ASPIRE study trial evaluated carfilzomib in combination with lenalidomide and low-dose dexamethasone, compared with lenalidomide and low-dose dexamethasone alone, in patients with relapsed multiple myeloma after treatment with one to three prior regimens. The study’s primary endpoint was progression-free survival (PFS), defined as the time from treatment initiation to disease progression or death. Secondary endpoints included overall survival (OS), the overall response rate, the duration of response, the disease control rate, health-related quality of life, and safety.

The patients were randomly assigned to receive carfilzomib (20 mg/m2 on days 1 and 2 of cycle 1 only, escalating to 27 mg/m2 on days 8, 9, 15, and 16 of cycle 1 and continuing on days 1, 2, 8, 9, 15, and 16 of subsequent cycles), in addition to a standard dosing schedule of lenalidomide (25 mg per day for 21 days on, 7 days off) and low-dose dexamethasone (40 mg per week in 4-week cycles) versus lenalidomide and low-dose dexamethasone alone. The study involved a total of 792 patients at sites in North America, Europe, and Israel.

PFS was significantly improved with carfilzomib compared with the control group (median: 26.3 months vs. 17.6 months, respectively; hazard ratio [HR] for progression or death, 0.69; P = 0.0001). The Kaplan–Meier 24-month OS rates were 73.3% and 65.0% in the carfilzomib and control groups, respectively (HR for death, 0.79; P = 0.04), and the rates of OS (partial response or better) were 87.1% and 66.7% (P < 0.001).

The data from the ASPIRE trial were presented at the 56th annual meeting of the American Society of Hematology in December 2014 and were published in the New England Journal of Medicine.

In July 2012, the FDA granted accelerated approval of Kyprolis for the treatment of patients with multiple myeloma who have received at least two prior therapies, including bortezomib and an immunomodulatory agent, and have demonstrated disease progression on or within 60 days of completion of the last therapy. Approval was based on the response rate. The clinical benefit of Kyprolis, such as an improvement in survival or symptoms, has not been verified in these patients.

Multiple myeloma is the second most common hematologic cancer and results from an abnormality of plasma cells, usually in the bone marrow. In the U.S., nearly 96,000 people have, or are in remission from, the disease. The estimated number of new cases of multiple myeloma in 2014 was more than 24,000, and the estimated number of deaths was 11,090.

Sources: Amgen; March 30, 2015; and NEJM; January 8, 2015.

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