The US Food and Drug Administration (FDA) has approved Amgen's supplemental New Drug Application (sNDA) of Kyprolis (carfilzomib) for injection in combination with dexamethasone or with lenalidomide plus dexamethasone for the treatment of patients with relapsed or refractory multiple myeloma who have received one to three lines of therapy.

The FDA also approved Kyprolis as a single agent for the treatment of patients with relapsed or refractory multiple myeloma who have received one or more lines of therapy. This FDA decision converts to full approval the initial accelerated approval Kyprolis received in July 2012 as a single agent.

"Kyprolis is the only approved therapy for relapsed multiple myeloma with proven efficacy as a single agent, doublet and triplet combination that is offered in a variety of doses to meet individual patient needs," said Sean E. Harper, M.D., executive vice president of research and development at Amgen. "Importantly, this new approval supports the use of Kyprolis as a backbone therapy for the management of relapsed multiple myeloma, a difficult-to-treat blood cancer."

"Multiple myeloma remains an incurable disease where relapse inevitably occurs and over time patients become resistant to treatments," said Dr. Ruben Niesvizky, director of the Multiple Myeloma Center at Weill Cornell Medicine and New York-Presbyterian/Weill Cornell Medical Center. "As a clinician, I'm pleased with the tremendous progress that we have seen in the past 12 months in multiple myeloma treatment. This FDA approval is important because it provides physicians with flexible options for Kyprolis use in helping to manage this challenging disease."

The approval is based on results from the phase 3 head-to-head ENDEAVOR study. This was a superiority trial in which the primary endpoint was progression-free survival (PFS). The data showed patients with relapsed multiple myeloma treated with Kyprolis and dexamethasone achieved 50 per cent greater PFS of 18.7 months compared to 9.4 months in those receiving Velcade (bortezomib) and dexamethasone (HR=0.53; 95 per cent CI: 044, 0.65 p<0.0001), a current standard of care in relapsed multiple myeloma. Patients in the study were treated until disease progression. The most common adverse reactions (greater than or equal to 20 per cent) in the Kyprolis arm were anaemia, diarrhoea, dyspnea, fatigue, insomnia, pyrexia and thrombocytopenia.

This new indication for Kyprolis is the second in six months. In July 2015, the FDA approved another expanded indication for Kyprolis in combination with lenalidomide and dexamethasone (KRd) for the treatment of patients with multiple myeloma who have received one to three prior lines of therapy.

Multiple myeloma is an incurable blood cancer, characterized by a recurring pattern of remission and relapse. It is a rare and very aggressive disease that accounts for approximately one percent of all cancers. In the US, there are nearly 90,000 people living with, or in remission from, multiple myeloma.  Approximately, 26,850 Americans are diagnosed with multiple myeloma each year and 11,240 patient deaths are reported on an annual basis.

The randomized ENDEAVOR (RandomizEd, OpeN Label, phase 3 study of Carfilzomib Plus DExamethAsone Vs Bortezomib Plus DexamethasOne in Patients With Relapsed Multiple Myeloma) trial of 929 patients evaluated Kyprolis in combination with low-dose dexamethasone (Kd), versus bortezomib with low-dose dexamethasone in patients whose multiple myeloma has relapsed after at least one, but not more than three prior therapeutic regimens. The primary endpoint of the trial was PFS, defined as the time from treatment initiation to disease progression or death. In a clinical trial, measuring the PFS is one way to demonstrate how well a treatment works.

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. 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. The irreversibility of Kyprolis' binding has also been shown to offer a more sustained inhibition of the targeted enzymes.

Kyprolis is approved in the US for: In combination with dexamethasone or with lenalidomide plus dexamethasone for the treatment of patients with relapsed or refractory multiple myeloma who have received one to three lines of therapy; As a single agent for the treatment of patients with relapsed or refractory multiple myeloma who have received one or more lines of therapy.

Kyprolis is also approved in Argentina, Israel, Kuwait, Mexico, Thailand, Colombia, Korea, Canada and the European Union. Additional regulatory applications for Kyprolis are underway and have been submitted to health authorities worldwide.

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