Amgen's Kyprolis Receives EU Approval, Officially Entering the European Market for Relapsed Multiple Myeloma
EU Approval and Regulatory History
The European Commission approved Amgen's (AMGN) Kyprolis (carfilzomib) on November 19, 2015, for adult patients with multiple myeloma who have received at least one prior therapy, in combination with lenalidomide and dexamethasone. The EMA's CHMP adopted a positive opinion on September 24 of the same year. Due to its recognition as being of significant public health interest, the accelerated review process shortened the review period from the usual 210 days to 150 days. In the United States, the FDA's Oncology Drugs Advisory Committee supported the benefit-risk balance by a vote of 11-0 with 1 abstention in June 2012, leading to accelerated approval in July 2012, and subsequent conversion to full approval on January 21, 2016, based on clinical benefit validation. In Japan, Ono Pharmaceutical (TSE:4528), which holds the local rights, obtained approval through PMDA review in July 2016, completing its entry into the three major regulatory regions.
Mechanism of Action and Phase 3 Clinical Evidence
Kyprolis is an intravenous formulation that irreversibly inhibits the chymotrypsin-like active site of the beta5 subunit of the 20S proteasome, inducing protein stress and cytotoxicity in myeloma cells. The pivotal Phase 3 ASPIRE study (NCT01080391), which supported the approval, compared Kyprolis, lenalidomide, and dexamethasone with lenalidomide and dexamethasone in 792 patients with relapsed multiple myeloma. The median progression-free survival was 26.3 months and 17.6 months, respectively, with a hazard ratio of 0.69 and a one-sided p-value of less than 0.0001, representing a 31% reduction in the risk of disease progression or death. Subsequent analysis also showed that the median overall survival was extended from 48.3 months to 40.4 months, demonstrating survival benefits beyond improved response rates.
Competitive Landscape and Market Potential
The main competitors are Velcade (bortezomib, a 20S proteasome inhibitor) from Takeda Pharmaceutical (TSE:4502), Darzalex (daratumumab, a CD38 antibody) from Johnson & Johnson (JNJ), and Revlimid (lenalidomide) from Bristol Myers Squibb (BMY). In relapsed disease, anti-CD38 antibodies, proteasome inhibitors, immunomodulatory agents, and BCMA-targeted cell and bispecific antibody therapies compete based on the line of therapy. Therefore, the position of Kyprolis depends on its flexibility in combination regimens and long-term survival data. According to Arcellx (ACLX), the global multiple myeloma market in 2025 is estimated at approximately USD 26 billion, and Amgen's Kyprolis sales in 2025 were USD 1.412 billion, a 6% decrease year-over-year. This indicates that while it maintains its blockbuster status, competition from new immunotherapies and generics is putting pressure on prescription volume.
Amgen's Asset Recovery and Investment Implications
In 2013, Amgen acquired Onyx Pharmaceuticals for a total of USD 10.4 billion, or USD 125 per share in cash, securing global rights to Kyprolis, excluding Japan. The EU approval was an event that expanded the base for converting Amgen's US-centric assets into global revenue streams and recovering the acquisition price of Onyx. Currently, the EU indication includes not only lenalidomide and dexamethasone, and dexamethasone alone, but also Darzalex and dexamethasone, and product lifecycle management is translating into actual prescription options. However, the 6% decrease in sales in 2025 clearly indicates that the line of therapy, the use of anti-CD38 antibodies, and the expansion of BCMA-targeted therapies will determine the future value of the asset, rather than the approval itself.
Kyprolis achieved EU approval and secured its position as a marketed combination therapy for relapsed multiple myeloma, demonstrating a median progression-free survival of 26.3 months versus 17.6 months and a hazard ratio of 0.69 in the Phase 3 ASPIRE trial. In the 2025 global market, estimated at approximately USD 26 billion, Amgen's product sales are USD 1.412 billion, but competition from Darzalex/Revlimid-based regimens and BCMA-targeted cell/bispecific antibody therapies is intensifying. For researchers and clinicians, the survival benefits of irreversible 20S proteasome inhibition and data on the management of cardiac, pulmonary, and renal toxicity are key factors in designing combination regimens. From an investment perspective, while the flagship asset acquired in the 2013 USD 10.4 billion Onyx acquisition maintains blockbuster sales, the 6% decrease in 2025 sales highlights that actual prescription volume and adoption in combination regimens in Europe are central variables for long-term value, rather than indication expansion alone.
Source: EMA (ema)