Ciltacabtagene autoleucel
- Generic Name
- Ciltacabtagene autoleucel
- Brand Names
- Carvykti
- Drug Type
- Biotech
- Unique Ingredient Identifier
- 0L1F17908Q
- Background
Multiple myeloma is a malignancy involving the plasma cells of the bone marrow. It is a rare malignancy, with an estimated yearly incidence of 6.5 people per 100,000, and is variable in its presentation - some patients may remain entirely asymptomatic, while others may experience a range of symptoms including bone pain, hematologic abnormalities, and end-organ damage. There have been a number of treatments developed for multiple myeloma (e.g. daratumumab), although none are curative.
B-cell maturation antigen (BCMA) is a transmembrane glycoprotein member of the tumor necrosis factor receptor superfamily 17 (TNFRSF17) which is used as a biomarker for multiple myeloma. While normally expressed on plasma blasts and plasma cells, BCMA is widely expressed on malignant plasma cells and most multiple myeloma cell lines, making it a choice target in the development of immunotherapies against multiple myeloma.
Ciltacabtagene autoleucel (Carvykti, Jannsen Biotech Inc.) is a BCMA-directed genetically modified autologous T-cell immunotherapy. Patient T-cells are reprogrammed with a transgene encoding a specific chimeric antigen receptor (CAR) which features two BCMA-targeting single-domain antibodies. Re-infusion of these modified T-cells leads to the targeted elimination of malignant plasma cells, on which BCMA is highly expressed. Carvykti was first approved by the FDA in February 2022 for the treatment of relapsed or refractory multiple myeloma in treatment-experienced patients.
- Indication
Ciltacabtagene autoleucel is indicated for the treatment of adult patients with relapsed or refractory multiple myeloma after ≥4 prior lines of therapy, including a proteasome inhibitor, an immunomodulatory agent, and an anti-CD38 monoclonal antibody.
- Associated Conditions
- Refractory Multiple Myeloma, Relapsed Multiple Myeloma
Thermo Fisher Scientific Launches First US Cell Therapy Collaboration Center in California
• Thermo Fisher Scientific has opened its first US Advanced Therapies Collaboration Center (ATxCC) in Carlsbad, California, designed to accelerate cell therapy development from research to commercialization.
• The 6,000-square-foot facility provides cell therapy developers access to cutting-edge technologies, specialized scientific support, and cGMP manufacturing expertise to overcome production challenges.
• This initiative addresses critical needs in the rapidly growing cell therapy market, projected to reach $48.54 billion by 2034, with plans for a second US center in Philadelphia later this year.
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.
Johnson & Johnson Commits $55 Billion to Expand U.S. Manufacturing and R&D Capabilities
• Johnson & Johnson announced a $55 billion investment over four years to expand U.S. manufacturing, R&D, and technology infrastructure, representing a 25% increase from previous spending.
• The company broke ground on a 500,000-square-foot biologics manufacturing facility in North Carolina, which will create 500 permanent positions and employ 5,000 during construction.
• This expansion follows similar U.S. manufacturing investments by Eli Lilly, Merck & Co., and Amgen, as pharmaceutical companies respond to tax incentives and growing demand for biologics.
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.
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• The COVID-19 pandemic has fundamentally transformed oncology care delivery, with telemedicine emerging as a permanent fixture that improves access while presenting challenges in patient assessment and reimbursement.
• Significant disruptions in cancer screenings during the pandemic have led to persistent stage migration, with oncologists reporting continued diagnoses of more advanced cancers across multiple tumor types.
• Clinical trial operations faced severe setbacks during the pandemic, with lingering effects on enrollment, staffing, and research progress, while oncologist burnout has increased from 45% in 2013 to 59% in 2023.
GSK's Blenrep Secures UK Approval for Multiple Myeloma Treatment in Combination Therapy
• The UK's medicines regulatory body has approved GSK's Blenrep (belantamab mafodotin) in combination with other drugs for multiple myeloma patients whose first treatment failed or caused severe side effects.
• This approval marks a significant comeback for Blenrep, which was withdrawn from markets in 2022 after failing to outperform existing treatments when used as monotherapy.
• Clinical trials demonstrated Blenrep's combination therapy extended progression-free survival and overall survival compared to standard care regimens, including those based on Darzalex (daratumumab).
Legend Biotech Reports Strong CARVYKTI® Growth with $963 Million in 2024 Sales, Treating Over 5,000 Patients
• Legend Biotech reported CARVYKTI® net trade sales of $963 million for full year 2024, with over 5,000 patients treated to date, positioning the CAR-T therapy as a market leader in multiple myeloma treatment.
• The company initiated commercial production at a Novartis facility and secured reimbursement approval from Spain's national health system for CARVYKTI® in second-line plus settings, expanding patient access.
• With $1.1 billion in cash reserves, Legend Biotech expects financial runway into Q2 2026, when it anticipates achieving operating profit excluding unrealized foreign exchange impacts.
FDA Tightens Requirements for China-Developed Drugs, Mandates Multi-Regional Trials
• The FDA has rejected multiple China-developed drugs, including Hutchmed's surufatinib and Eli Lilly's sintilimab, citing concerns over single-country clinical trial data.
• At least 25 oncology drug applications from China face increased scrutiny, with the FDA emphasizing the need for multi-regional trials to ensure data generalizability across diverse populations.
• The regulatory shift impacts China's growing biopharma sector, which has attracted significant Western partnerships, including Merck's recent $1.4 billion deal with Sichuan Kelun Pharmaceutical.
CAR T-cell Therapies Show Promise in Relapsed Multiple Myeloma
• Allogeneic BCMA CAR T-cell therapy demonstrates promising efficacy and reasonable safety in relapsed multiple myeloma, utilizing CRISPR technology to mitigate graft-versus-host disease.
• A clinical trial targeting GPRC5D shows high efficacy in patients who have relapsed after BCMA-targeted therapy, potentially offering a more favorable treatment option.
• The allogeneic approach allows for faster treatment delivery using "off-the-shelf" cells, addressing a key limitation of autologous CAR T-cell therapies.
• Early results indicate high efficacy in minority patients, who are often underrepresented in clinical trials, highlighting the therapy's potential for broader impact.
J&J's Carvykti Shows Promise in Earlier Myeloma Treatment
• The CARTITUDE-4 study indicates that Carvykti (ciltacabtagene autoleucel) significantly improves progression-free survival in multiple myeloma patients with 1-3 prior lines of therapy.
• Carvykti, a BCMA-directed CAR-T therapy, may soon be used earlier in the treatment pathway, potentially leapfrogging Bristol-Myers Squibb's Abecma.
• The study compared Carvykti to standard three-drug regimens, showing a significant benefit that led to unblinding of the trial.
• Expansion of Carvykti's use is a key component of J&J's strategy in multiple myeloma, alongside other therapies like Darzalex and bispecific antibodies.
CAR T-Cell Therapy Shows Promise in Treating Autoimmune Diseases: Clinical Trials and Future Directions
• UChicago Medicine launched a Phase 2 clinical trial to explore CAR T-cell therapy for systemic lupus erythematosus, inflammatory myositis, and systemic sclerosis.
• CAR T-cell therapy, initially for blood cancers, is being adapted to autoimmune diseases, potentially offering a new solution for resistant cases.
• BMS reported promising Phase 1 trial results using CD19 CAR T-cells for severe autoimmune diseases, showing significant disease activity reduction.
• Researchers are optimistic about CAR T-cell therapy's potential to 'reset' the immune system, but emphasize the need for long-term data and safety monitoring.
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.
FDA to Review Belantamab Mafodotin and Linvoseltamab Combinations for Multiple Myeloma
• The FDA has accepted a BLA for belantamab mafodotin combinations with bortezomib plus dexamethasone and pomalidomide plus dexamethasone for multiple myeloma treatment.
• Regeneron's linvoseltamab BLA resubmission has been accepted by the FDA, with a decision expected by July 10, 2025, for relapsed/refractory multiple myeloma.
• Clinical trials DREAMM-7 and DREAMM-8 support the belantamab mafodotin BLA, while LINKER-MM1 supports the linvoseltamab BLA, showcasing improved progression-free survival.
• Both belantamab mafodotin and linvoseltamab are under review by other regulatory authorities, potentially expanding treatment options for multiple myeloma patients.
GSK's Blenrep Demonstrates Significant Survival Benefit in Multiple Myeloma Trial, Paving Way for Potential Comeback
• GSK's Blenrep, combined with chemotherapy and a steroid, reduced the risk of death by 42% compared to a standard-of-care treatment in relapsed or refractory multiple myeloma.
• The DREAMM-7 trial data showed a projected median overall survival of 84 months for the Blenrep combination versus 51 months for the comparator arm.
• Blenrep, an antibody-drug conjugate targeting BCMA, is under regulatory review in multiple regions, potentially offering a new treatment option for myeloma patients.
• Despite previous market withdrawal due to a failed trial, Blenrep's new data suggests a possible paradigm shift in treating relapsed or refractory multiple myeloma.
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