Idecabtagene vicleucel
- Generic Name
- Idecabtagene vicleucel
- Brand Names
- Abecma
- Drug Type
- Biotech
- Unique Ingredient Identifier
- 8PX1X7UG4D
- Background
Multiple myeloma is a cancer where plasma cells rapidly divide out of control. These cancerous cells generally express the B-cell maturation antigen, while it is rarely expressed on non-cancerous cells. Multiple myeloma is typically treated with an immunomodulatory agent like lenalidomide, a proteasome inhibitor like bortezomib, or an anti-CD38 monoclonal antibody like isatuximab.
Idecabtagene vicleucel, also known as bb2121, is a chimeric antigen receptor (CAR) T-cell therapy like axicabtagene ciloleucel and brexucabtagene autoleucel. These therapies involve extracting and genetically manipulating T-cells from a patient to express a CAR for a tumor specific antigen. The chimeric antigen receptor of idecabtagene vicleucel includes an anti-B-cell maturation antigen scFv-targeting domain, CD3ζ T-cell activation domain, and 4-1BB costimulatory domain. Idecabtagene vicleucel is indicated as a fifth line treatment of adult patients with relapsed or refractory multiple myeloma.
Idecabtagene vicleucel was granted FDA approval on 26 March 2021.
- Indication
Idecabtagene vicleucel is indicated to treat adult patients with relapsed or refractory multiple myeloma who have tried at least 4 other lines of therapy, including an immunomodulatory agent, proteasome inhibitor, and anti-CD38 monoclonal antibody.
- Associated Conditions
- Refractory Multiple Myeloma, Relapsed Multiple Myeloma
Anito-cel Shows Promise as Novel BCMA-Targeted CAR T Therapy for Multiple Myeloma
• Anitocabtagene autoleucel (anito-cel) utilizes a novel D-Domain binder for BCMA targeting, offering potentially higher transduction efficiency and CAR density compared to traditional CAR T therapies.
• Early clinical data from the iMMagine-1 trial demonstrates high response rates (95-100%) in heavily pretreated multiple myeloma patients, with no delayed neurotoxicities reported to date.
• While currently being studied in later-line settings for triple-class exposed patients, ongoing trials may determine if BCMA-targeted CAR T therapies like anito-cel could move to earlier treatment lines.
BMS's Opdualag Shows Strong Early Performance as First LAG-3 Checkpoint Inhibitor for Melanoma
• Bristol-Myers Squibb's Opdualag, the first FDA-approved LAG-3 inhibitor combination, generated $58 million in second-quarter sales following its March approval for metastatic melanoma.
• Clinical data shows Opdualag more than doubles progression-free survival compared to PD-1 monotherapy, positioning it as a potential new standard of care with anticipated EU approval in coming weeks.
• BMS expects Opdualag to reach $4 billion in peak sales across multiple cancer indications, strengthening its immuno-oncology portfolio as competitors including Merck develop rival LAG-3 inhibitors.
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).
Bristol Myers Squibb Acquires 2seventy bio for $286 Million to Gain Full Control of CAR-T Therapy Abecma
• Bristol Myers Squibb has agreed to acquire 2seventy bio for $286 million, ending the profit-sharing arrangement for the BCMA-targeted CAR-T therapy Abecma used in multiple myeloma treatment.
• The acquisition represents an 88% premium over 2seventy's closing share price but marks the end of a challenging journey for the cell therapy company, which was spun out from bluebird bio in 2021.
• BMS's strategic move aligns with its cost-cutting initiatives aimed at saving $3.5 billion through 2027, as the company faces patent expirations for key products including Opdivo, Yervoy, and Eliquis.
Biotech Deal Landscape: February-March 2025 Sees Surge in Partnerships Across Multiple Therapeutic Areas
• The first quarter of 2025 witnessed significant biotech partnership activity, with Eli Lilly, AstraZeneca, and Novo Nordisk emerging as top collaborators in deals worth billions across small molecules, antibodies, and RNA therapeutics.
• February 2025 featured notable acquisitions including Novartis's $2.15 billion buyout of Anthos Therapeutics, while March saw AstraZeneca acquire Belgian biotech EsoBiotec and Bristol Myers Squibb purchase 2seventy bio for $286 million.
• Obesity therapeutics gained significant traction in March 2025, with AbbVie entering the field through a $350 million upfront deal with Gubra for an amylin analog, while Roche partnered with Zealand Pharma on petrelintide in a deal worth up to $5.25 billion.
CAR T-cell Therapy Pipeline Surges with 180+ Companies Advancing Novel Cancer Treatments
• The CAR T-cell therapy pipeline has experienced significant growth, with over 180 companies actively developing more than 200 innovative cell therapy candidates across various stages of clinical development.
• Recent breakthroughs include Hemogenyx's first human administration of HG-CT-1 for acute myeloid leukemia and NICE's approval of lisocabtagene maraleucel for large B-cell lymphoma treatment.
• Strategic industry developments are accelerating progress, with companies like CARsgen Therapeutics forming alliances to advance allogeneic CAR-T products and multiple firms reporting successful trial milestones.
Atara Biotherapeutics' Ebvallo Nears EU Approval for Transplant Complication Therapy
Atara Biotherapeutics' cell therapy, Ebvallo, is on the verge of becoming the first allogeneic T-cell therapy approved globally, targeting Epstein-Barr virus-positive post-transplant lymphoproliferative disease (EBV+ PTLD). The EMA's human medicines committee has recommended its approval as a second-line therapy, showing promising results in clinical trials with a 50% overall response rate and a significant improvement in one-year survival rates among responders.
Breyanzi Receives Positive CHMP Opinion for Follicular Lymphoma Treatment in EU
• The CHMP has recommended Breyanzi for treating relapsed or refractory follicular lymphoma (FL) in adults after two or more prior systemic therapies.
• The recommendation is based on the Phase 2 TRANSCEND FL study, which showed a 97.1% overall response rate and a 94.2% complete response rate.
• Breyanzi demonstrated rapid and durable responses, with 75.7% of patients in response at 18 months, and a consistent safety profile in clinical trials.
• The European Commission will review the CHMP recommendation, with a final decision expected within approximately two months.
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.
FDA Approves Subcutaneous Opdivo Qvantig for Multiple Solid Tumors
• The FDA approved Opdivo Qvantig, a subcutaneous injection of nivolumab, for adult solid tumors previously approved for intravenous Opdivo.
• CheckMate-67T trial data showed non-inferior pharmacokinetic exposures, similar efficacy, and comparable safety to intravenous Opdivo.
• Opdivo Qvantig offers a faster 3-5 minute administration time, providing convenience and flexibility for patients.
• The approval helps Bristol Myers Squibb maintain market share amid patent expirations and increasing biosimilar competition.
Real-World Data Reinforces Cilta-Cel Efficacy in Relapsed Multiple Myeloma, While Ide-Cel Shows Promise in CNS Involvement
• Real-world evidence confirms cilta-cel's effectiveness in relapsed/refractory multiple myeloma, mirroring clinical trial outcomes with high response rates and durable remission.
• A significant portion of patients in the real-world study wouldn't have met clinical trial eligibility, highlighting cilta-cel's potential in a broader patient population.
• Ide-cel demonstrates promising results in patients with CNS involvement of multiple myeloma, showing favorable responses and manageable safety profiles in a retrospective analysis.
• Renal impairment does not significantly impact the efficacy of BCMA-targeting CAR T-cell therapies in relapsed/refractory multiple myeloma, though increased monitoring for ICANS and infections may be warranted.
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.
Cytokinetics' Aficamten Advances in Regulatory Review for Obstructive Hypertrophic Cardiomyopathy
• The EMA has validated Cytokinetics' Marketing Authorization Application (MAA) for aficamten, a cardiac myosin inhibitor, for treating obstructive hypertrophic cardiomyopathy (HCM).
• The FDA has accepted the New Drug Application (NDA) for aficamten with a PDUFA target action date of September 26, 2025, and no advisory committee meeting is planned.
• Aficamten significantly improved exercise capacity and clinical outcomes in the SEQUOIA-HCM Phase 3 trial, supporting regulatory submissions in the U.S., Europe, and China.
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.
Bristol Myers Squibb Receives Positive CHMP Opinions for Opdivo, Yervoy, and Breyanzi
• The CHMP recommended Opdivo plus Yervoy for first-line treatment of unresectable or advanced hepatocellular carcinoma (HCC) in adults, based on the CheckMate -9DW trial.
• Breyanzi received a positive CHMP opinion for relapsed or refractory follicular lymphoma after two or more prior systemic therapies, showing a 97.1% response rate in the TRANSCEND FL study.
• Opdivo plus Yervoy also received a positive CHMP opinion for first-line treatment of MSI-H or dMMR metastatic colorectal cancer, demonstrating a 79% reduction in disease progression or death risk.
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.
Bispecific Antibodies Teclistamab and Talquetamab Show Promise in Multiple Myeloma Treatment
• Teclistamab and talquetamab, bispecific antibodies, demonstrate efficacy in relapsed/refractory multiple myeloma by reducing soluble BCMA levels in responding patients.
• A reduction in sBCMA levels correlates with the depth of treatment response, with complete or stringent complete responses showing nearly 100% sBCMA reduction.
• Baseline sBCMA levels correlate with tumor burden, suggesting sBCMA as a potential marker, and do not significantly affect teclistamab exposure, indicating maintained clinical activity.
• Clinical trials are underway to evaluate bispecific antibodies in earlier lines of therapy and maintenance settings, potentially transforming myeloma treatment.
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