Carfilzomib
- Generic Name
- Carfilzomib
- Brand Names
- Kyprolis
- Drug Type
- Small Molecule
- Chemical Formula
- C40H57N5O7
- CAS Number
- 868540-17-4
- Unique Ingredient Identifier
- 72X6E3J5AR
- Background
Carfilzomib is an injectable antineoplastic agent (IV only). Chemically, it is a modified tetrapeptidyl epoxide and an analog of epoxomicin. It is also a selective proteasome inhibitor. FDA approved carfilzomib in July 2012 for the treatment of adults with relapsed or refractory multiple myeloma as monotherapy or combination therapy.
- Indication
Carfilzomib is indicated for the treatment of adult patients with relapsed or refractory multiple myeloma who have received one to three lines of therapy in combination with lenalidomide and dexamethasone; or dexamethasone; or daratumumab and dexamethasone; or daratumumab and hyaluronidase-fihj and dexamethasone; or isatuximab and dexamethasone. It is also indicated as a single agent for the treatment of patients with relapsed or refractory multiple myeloma who have received one or more lines of therapy.
- Associated Conditions
- Relapsed/Refractory Multiple Myeloma (RRMM)
FDA's Approval of MRD as End Point Transforms Multiple Myeloma Research and Treatment
• The FDA's Oncology Drugs Advisory Committee unanimously approved minimal residual disease (MRD) as an end point for accelerated approval of multiple myeloma therapies in April 2024, potentially reducing trial timelines from 10-15 years to just 3 years.
• Pharmaceutical companies have rapidly adapted by implementing MRD as a coprimary end point in new trials and amending existing protocols, with the CEPHEUS trial being the first major study to read out with MRD as a coprimary endpoint.
• Researchers are now exploring MRD applications beyond drug approval, including using MRD status to guide treatment decisions, developing improved blood-based detection technologies, and expanding the approach to other hematologic malignancies.
Amgen Reports Strong Global Demand in Q1 2025, Bolstering Long-Term Growth Outlook
• Amgen announced positive first quarter 2025 financial results, citing strong global demand across its product portfolio and successful new product launches.
• Chairman and CEO Bob Bradway expressed confidence in Amgen's long-term growth prospects, supported by recent successful Phase 3 clinical trial results for several products.
• The biotechnology company, which employs over 28,000 people globally, continues to focus on its mission of harnessing biology and technology to combat serious diseases.
Trump's Executive Order Delays Medicare Drug Price Negotiations, Sparking Industry and Policy Debate
• President Trump signed an executive order extending the exemption period for small-molecule drugs from Medicare price negotiations by four years, a move criticized by advocacy groups as favoring pharmaceutical industry interests.
• The order aims to address what the administration calls the "pill penalty" - the current policy where small-molecule drugs (90% of medications) face negotiations after 9 years while biologics have longer exemption periods.
• The Medicare Drug Price Negotiation Program, established under the Biden administration, had already achieved price reductions of 38-79% on 10 high-cost drugs with projected savings of $6 billion if applied in 2023.
DARZALEX Dominates Multiple Myeloma Market with $11.6 Billion in Global Sales
• DARZALEX (daratumumab), Janssen's CD38-targeting monoclonal antibody, has transformed multiple myeloma treatment across all lines of therapy, generating $11.6 billion in worldwide sales in 2024.
• The drug's success stems from its versatility in combination regimens, expanded approvals for both newly diagnosed and relapsed/refractory patients, and the introduction of DARZALEX FASPRO, a convenient subcutaneous formulation.
• Despite growing competition from emerging therapies like Sanofi's SARCLISA and novel BCMA-targeting agents, DARZALEX maintains market leadership through first-mover advantage and robust clinical efficacy data.
Optimizing Treatment Strategies for Relapsed Multiple Myeloma: From CAR T-Cell Therapy to Novel Combinations
• CAR T-cell therapy has emerged as a valuable option for multiple myeloma patients after first relapse when they are lenalidomide-refractory, with careful consideration needed for pre-treatment strategies to optimize outcomes.
• Experts recommend avoiding BCMA-targeted therapies before BCMA-directed CAR T-cell therapy, as this can lead to lower response rates and progression-free survival, while non-BCMA bispecifics like talquetamab may be effective bridging options.
• Selinexor-based combinations, including selinexor/pomalidomide/dexamethasone and selinexor/carfilzomib/dexamethasone, show promising efficacy in heavily pretreated patients with response rates of 50-65% and progression-free survival ranging from 6-15 months.
Sarclisa (Isatuximab) Shows Promise in Multiple Myeloma Treatment: China Approval and Subcutaneous Formulation Advances
• China's NMPA has approved Sarclisa (isatuximab) in combination with pomalidomide and dexamethasone for relapsed/refractory multiple myeloma, marking a significant milestone for Sanofi.
• A Phase 3 IRAKLIA trial demonstrated that subcutaneous isatuximab, delivered via an on-body system, achieved non-inferior objective response rates compared to intravenous administration.
• Regulatory submissions for subcutaneous isatuximab are planned in the US and EU in the first half of 2025, potentially offering a more convenient administration option for patients.
CAR-T Therapies Idecabtagene Vicleucel and Ciltacabtagene Autoleucel Show Promise in Multiple Myeloma Treatment
• Idecabtagene vicleucel (ide-cel) demonstrated high rates of complete response and minimal residual disease negativity in multiple myeloma patients after suboptimal response to standard first-line therapy.
• Ciltacabtagene autoleucel (cilta-cel) showed significantly higher rates of minimal residual disease negativity compared to standard of care in lenalidomide-refractory multiple myeloma.
• Cilta-cel's sustained MRD negativity translated to prolonged progression-free survival, with over 93% of patients remaining progression-free for more than 30 months.
• Both ide-cel and cilta-cel highlight the potential of CAR-T cell therapy in achieving deep and durable responses in multiple myeloma patients.
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Isatuximab Combinations Show Promise in Newly Diagnosed Multiple Myeloma
• Isatuximab plus VRd significantly reduced disease progression or death risk by 40.4% in transplant-ineligible newly diagnosed multiple myeloma patients.
• The FDA approved isatuximab-irfc with VRd for transplant-ineligible multiple myeloma, based on the IMROZ trial data.
• Isatuximab-RVd induction therapy improved progression-free survival in transplant-eligible newly diagnosed multiple myeloma patients, GMMG-HD7 trial showed.
• The addition of isatuximab to RVd led to higher rates of minimal residual disease negativity, indicating deeper responses.
European Commission Approves Sanofi's Sarclisa with VRd for Newly Diagnosed Multiple Myeloma
• The European Commission has approved Sarclisa (isatuximab-irfc) in combination with bortezomib, lenalidomide, and dexamethasone (VRd) for treating newly diagnosed multiple myeloma (NDMM) in adults not eligible for autologous stem cell transplant (ASCT).
• This approval marks Sarclisa as the first anti-CD38 therapy in the EU combined with VRd for transplant-ineligible NDMM patients, expanding its use beyond relapsed/refractory settings.
• The decision is based on the Phase 3 IMROZ study, which demonstrated a significant improvement in progression-free survival (PFS) with the Sarclisa-VRd combination compared to VRd alone.
• Sanofi continues to develop Sarclisa with ongoing Phase 2 and 3 trials, including exploring a subcutaneous delivery system to enhance patient comfort and convenience.
MRD Negativity Sustained After Lenalidomide Cessation in Multiple Myeloma
• A recent study presented at the 21st International Myeloma Society Annual Meeting showed that MRD negativity was maintained for at least one year after stopping lenalidomide maintenance in multiple myeloma patients.
• The study found that 85% of evaluable patients maintained MRD negativity 12 months after cessation of lenalidomide maintenance therapy.
• Findings suggest that stopping maintenance therapy may be feasible in patients with 3-year sustained MRD negativity, potentially improving quality of life and reducing financial burden.
• Researchers look forward to further data from the SWOG 1803/DRAMMATIC trial, which is randomly assigning patients to maintenance continuation vs discontinuation.
J&J Seeks EMA Approval for Darzalex SC Quadruplet Regimen in Newly Diagnosed Multiple Myeloma
• Janssen-Cilag International NV has submitted a Type II variation application to the EMA for DARZALEX SC in combination with bortezomib, lenalidomide, and dexamethasone (D-VRd).
• The submission is supported by the Phase 3 CEPHEUS study, which showed a 60.9% MRD-negativity rate with D-VRd and a 43% reduction in the risk of progression or death.
• The CEPHEUS study evaluated D-VRd compared to VRd in NDMM patients ineligible for transplant or for whom ASCT was not planned as initial therapy.
• If approved, the D-VRd combo could be used as a first-line therapy regardless of patients’ transplant eligibility, improving long-term outcomes.
Sarclisa Approved for First-Line Multiple Myeloma Treatment in Transplant-Ineligible Patients
• The FDA has approved Sarclisa (isatuximab) in combination with bortezomib, lenalidomide, and dexamethasone (VRd) as a first-line treatment for transplant-ineligible multiple myeloma.
• The approval was based on the IMROZ phase 3 trial, which showed a 40% reduction in disease progression or death compared to VRd alone.
• Sarclisa is the first anti-CD38 therapy approved with VRd for this patient population, offering a new standard of care.
• The combination demonstrated high rates of complete response and minimal residual disease negativity, improving long-term outcomes.
Significant Improvement in Progression-Free Survival with SARCLISA Combination Therapy for Previously Treated Multiple Myeloma
A Phase 3 trial reveals that patients with previously treated multiple myeloma who stopped responding to Revlimid experienced a median progression-free survival of 41.7 months with SARCLISA combined with Kyprolis and dexamethasone, compared to 20.8 months with Kyprolis and dexamethasone alone.
Drug Development Updates
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