Bortezomib
- Generic Name
- Bortezomib
- Brand Names
- Velcade, Bortezomib Accord, Bortezomib Hospira, Bortezomib Fresenius Kabi, Bortezomib Sun
- Drug Type
- Small Molecule
- Chemical Formula
- C19H25BN4O4
- CAS Number
- 179324-69-7
- Unique Ingredient Identifier
- 69G8BD63PP
- Background
Bortezomib is a dipeptide boronic acid derivative and proteasome inhibitor used to treat multiple myeloma and mantle cell lymphoma. The 26S proteasome is a protein complex that degrades ubiquitinated proteins in the ubiquitin-proteasome pathway: reversible inhibition of the 26S proteasome, leading to cell cycle arrest and apoptosis of cancer cells, is thought to be the main mechanism of action of bortezomib. However, multiple mechanisms may be involved in the anticancer activity of bortezomib.
Bortezomib was first synthesized in 1995. In May 2003, bortezomib became the first anticancer proteasome inhibitor that was approved by the FDA under the trade name VELCADE. Phase I, II, III, and IV clinical trials are undergoing to investigate the therapeutic efficacy of bortezomib in leukemia, myasthenia gravis, systemic lupus erythematosus, rheumatoid arthritis, and solid tumours.
- Indication
Bortezomib is indicated for the treatment of adults with multiple myeloma or mantle cell lymphoma.
- Associated Conditions
- Mantle Cell Lymphoma (MCL), Multiple Myeloma (MM)
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.
Balancing Efficacy and Cost Sustainability in Modern CLL Treatment: Insights from Dr. Pierluigi Porcu
• Clinicians treating chronic lymphocytic leukemia (CLL) face growing challenges in balancing clinical efficacy with long-term cost sustainability, requiring a holistic approach to patient care.
• Dr. Pierluigi Porcu emphasizes that effective CLL management requires understanding disease risk, patient comorbidities, and practice environment constraints including payer considerations.
• Despite its importance, value-based care adoption remains insufficient in oncology, with challenges in defining and measuring value across patient outcomes, quality of life, and treatment costs.
Amneal Launches Boruzu: First Ready-to-Use Bortezomib Injection for Multiple Myeloma Treatment
• Amneal Pharmaceuticals and Shilpa Medicare have launched Boruzu, the first ready-to-use bortezomib formulation for subcutaneous or intravenous administration in multiple myeloma and mantle cell lymphoma treatment.
• The innovative formulation eliminates reconstitution steps required with the reference product Velcade, potentially streamlining clinical workflow and reducing patient wait times.
• Boruzu represents Amneal's fourth 505(b)(2) injectable product launch in the past year, featuring a unique J-code to facilitate reimbursement as part of the company's strategy to build a portfolio of complex injectable products.
Pomalidomide-Based Combinations Show Promising Efficacy in Relapsed/Refractory Multiple Myeloma
• Recent clinical trials demonstrate that pomalidomide-based regimens yield significant benefits for patients with relapsed/refractory multiple myeloma, particularly after lenalidomide treatment failure.
• The phase 3 OPTIMISMM trial showed PVd (pomalidomide, bortezomib, dexamethasone) extended median progression-free survival to 11.7 months versus 6.9 months with Vd alone, with benefits observed across high-risk subgroups.
• A phase 2 trial found that adding elotuzumab to PVd produced a 56.3% overall response rate in heavily pretreated patients, with particularly strong results (73.7% ORR) in those with only one prior line of therapy.
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.
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).
DARZALEX® Subcutaneous Regimen Receives CHMP Backing for Newly Diagnosed Multiple Myeloma Treatment
• Johnson & Johnson's DARZALEX® subcutaneous formulation combined with VRd receives positive CHMP recommendation for treating newly diagnosed multiple myeloma patients, regardless of transplant eligibility.
• The recommendation is supported by the Phase 3 CEPHEUS study, which evaluated the efficacy of daratumumab-VRd compared to VRd alone in 395 patients with newly diagnosed multiple myeloma.
• DARZALEX® has demonstrated significant impact in multiple myeloma treatment, having been used in over 618,000 patients worldwide and currently approved in eight indications.
Clinical Trial Diversity Crisis: Black Patients Severely Underrepresented in Multiple Myeloma Studies
• Recent phase 3 trials IMROZ and PERSEUS for multiple myeloma treatments showed alarming diversity gaps, with Black patients comprising only 0.9% and 1.3% of participants despite representing 20% of new myeloma cases.
• FDA study of 32,000 clinical trial participants reveals significant racial disparities, with non-Hispanic Whites overrepresented at 75% while Hispanic and Black populations remain underrepresented relative to US demographics.
• Real-world multiple myeloma patients show 44% worse progression-free survival compared to clinical trial participants, highlighting the consequences of non-representative trial populations.
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.
Dogwood Therapeutics Initiates Phase 2b Trial of Halneuron® for Chemotherapy-Induced Neuropathic Pain
• Dogwood Therapeutics has commenced patient dosing in a Phase 2b trial (HALT-CINP) to evaluate Halneuron® for chemotherapy-induced neuropathic pain (CINP).
• Halneuron®, a first-in-class Nav 1.7 inhibitor, offers a non-opioid alternative for managing chronic pain associated with chemotherapy.
• The trial targets a significant unmet medical need, with the CINP market estimated at $1.5 billion, addressing the ineffectiveness of current treatments.
• Interim data from the Phase 2 CINP study are anticipated in the second half of 2025, marking a key milestone for the drug's development.
Acalabrutinib Receives FDA Approval for Previously Untreated Mantle Cell Lymphoma
• The FDA has granted traditional approval to acalabrutinib in combination with bendamustine and rituximab for untreated MCL patients ineligible for stem cell transplant.
• The approval was based on the ECHO trial, which showed a 27% reduction in disease progression or death compared to chemoimmunotherapy alone.
• Median progression-free survival was 66.4 months with acalabrutinib versus 49.6 months with chemoimmunotherapy, demonstrating a clinically significant improvement.
• Acalabrutinib is now the first and only BTK inhibitor approved for first-line MCL treatment, offering a new option for this rare and aggressive cancer.
Karyopharm's Selinexor Shows Promise in Myelofibrosis, Phase 3 Data Expected in 2H 2025
• Karyopharm Therapeutics anticipates top-line results from its Phase 3 SENTRY trial of selinexor plus ruxolitinib for JAKi-naïve myelofibrosis in the second half of 2025.
• The SENTRY trial updated its co-primary endpoint to absolute mean change in total symptom score (Abs-TSS) and increased the sample size to 350 patients.
• Preliminary 2024 results show total revenue of approximately $145 million, with XPOVIO net product revenue reaching $113 million for Karyopharm.
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.
Kymriah Receives EU Approval as First CAR-T Therapy for Follicular Lymphoma
• Novartis' Kymriah is the first CAR-T therapy approved in the EU for relapsed/refractory follicular lymphoma, offering a new option for patients after multiple treatments.
• The approval was based on the ELARA trial, demonstrating an 86% response rate and 69% complete response rate in patients treated with Kymriah.
• Kymriah provides durable treatment effects, with 87% of complete responders remaining in remission for at least nine months after initial response.
• This approval expands Kymriah's indications in the EU, adding to its existing approvals for diffuse large B-cell lymphoma and acute lymphoblastic leukemia.
AbbVie's Vyalev for Parkinson's Disease Incorporates Key Innovations from KU Chemist
• Vyalev, a new subcutaneous drug therapy by AbbVie for Parkinson's disease, has been approved by the FDA in October 2024 after successful Phase 3 trials.
• The therapy uses a wearable pump to deliver levodopa/carbidopa, providing consistent dosage and reducing motor fluctuations in Parkinson's patients.
• University of Kansas chemist Valentino Stella contributed to the drug's development by discovering forms of L-dopa and carbidopa suitable for infusion.
• Clinical trials showed Vyalev significantly increased 'on' time (optimal motor control) and decreased 'off' time (return of symptoms) compared to oral treatments.
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.
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ASH 2024: Updates on Daratumumab, Selinexor, and Asciminib Highlighted
• Long-term follow-up data from the phase 3 AQUILA study will explore daratumumab monotherapy's efficacy in delaying progression in high-risk smoldering multiple myeloma.
• Updated results from the phase 1b/2 STOMP trial will present 96-week data on selinexor plus pomalidomide and dexamethasone in multiple myeloma.
• The ASH meeting will feature a 96-week data update from the phase 3 ASC4FIRST trial, assessing asciminib as a first-line treatment for CML-CP.
Daratumumab Plus VRd Improves Outcomes in Transplant-Ineligible Multiple Myeloma Patients
• The phase 3 CEPHEUS trial demonstrated that adding daratumumab to VRd significantly improved outcomes for transplant-ineligible newly diagnosed multiple myeloma patients.
• The quadruplet regimen achieved a 60.9% minimal residual disease (MRD) negativity rate compared to 39.4% with VRd alone, demonstrating a significant increase in treatment depth.
• Progression-free survival was also significantly improved with the daratumumab regimen, showing a 43% reduction in the risk of disease progression or death.
• These results suggest that daratumumab plus VRd could become a new standard of care for transplant-ineligible multiple myeloma patients, offering improved disease control.
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