Amgen and its subsidiary Onyx Pharmaceuticals announced the submission of a supplemental New Drug Application (sNDA) to the US Food and Drug Administration (FDA) and a Marketing Authorisation Application (MAA) to the European Medicines Agency (EMA) for Kyprolis (carfilzomib) for injection to seek approval for the treatment of patients with relapsed multiple myeloma who have received at least one prior therapy. In the US, the sNDA is designed to support the conversion of accelerated approval to full approval and expand the current approved indication. In the European Union (EU), Kyprolis received orphan drug designation and the MAA has been granted accelerated assessment.

The sNDA and MAA are based on data from the phase 3 ASPIRE (CArfilzomib, Lenalidomide, and DexamethaSone versus Lenalidomide and Dexamethasone for the treatment of Patients with Relapsed Multiple MyEloma) trial and other relevant data.

“Multiple myeloma is an incurable blood cancer that often becomes resistant to treatment, underscoring the need for new therapeutic options that provide deep and durable responses to extend the time patients live without their disease progressing,” said Pablo J. Cagnoni, MD, president, Onyx Pharmaceuticals, Inc. "The US and EU submissions support our goal of bringing Kyprolis to patients with relapsed multiple myeloma."

Orphan designation is granted by the EMA for medicines intended for the treatment, prevention or diagnosis of a disease that is life threatening and has a prevalence in the EU of no more than five in 10,000. The intended medicine must aim to provide significant benefit to those affected by the condition.

Kyprolis is in a class of drugs called proteasome inhibitors and was granted accelerated approval by the FDA in 2012. Kyprolis is also approved for use in Argentina, Israel and Mexico.

Multiple myeloma is the second most common hematologic cancer and results from an abnormality of plasma cells, usually in the bone marrow. Worldwide, nearly 230,000 people are living with multiple myeloma. In 2012, approximately 114,000 new cases were diagnosed and 80,000 people died. In the US, approximately 83,000 people were living with multiple myeloma in 2011. The estimated number of new cases in 2014 was 24,000 and the estimated number of deaths was 11,000. In Europe, approximately 89,000 people are living with multiple myeloma. Approximately 39,000 new cases were diagnosed and 24,000 people died in 2012.

The international, randomised phase 3 ASPIRE (CArfilzomib, Lenalidomide, and DexamethaSone versus Lenalidomide and Dexamethasone for the treatment of Patients with Relapsed Multiple MyEloma) trial evaluated Kyprolis in combination with lenalidomide and low-dose dexamethasone, versus lenalidomide and low-dose dexamethasone alone, in patients with relapsed multiple myeloma following treatment with one to three prior regimens. The primary endpoint of the trial was progression-free survival, defined as the time from treatment initiation to disease progression or death. Secondary endpoints included overall survival, overall response rate, duration of response, disease control rate, health-related quality of life and safety. Patients were randomiszed to receive Kyprolis (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 randomised 792 patients at sites in North America, Europe and Israel.

Onyx Pharmaceuticals conducted the ASPIRE trial under a Special Protocol Assessment (SPA) from the FDA and received Scientific Advice from the EMA on the design and planned analysis of the study.

On July 20, 2012, the US FDA granted accelerated approval of Kyprolis (carfilzomib) for Injection for the treatment of patients with multiple myeloma who have received at least two prior therapies including bortezomib and an immunomodulatory agent (IMiD) and have demonstrated disease progression on or within 60 days of completion of the last therapy. Approval was based on response rate. Clinical benefit, such as improvement in survival or symptoms, has not been verified.

Kyprolis is a product of Onyx Pharmaceuticals, Inc. Onyx Pharmaceuticals is a subsidiary of Amgen and holds development and commercialisation rights to Kyprolis globally, excluding Japan.