Zanubrutinib vs acalabrutinib 2023 Dec;98(12):E387-E390. 0% vs 74. Acalabrutinib (Calquence) and zanubrutinib (Brukinsa) demonstrated similar investigator-assessed progression-free survival (PFS) in patients with relapsed/refractory chronic lymphocytic leukemia Key Takeaways. It’s important to note that acalabrutinib is associated with a high incidence of Efficacy of Zanubrutinib Versus Acalabrutinib in the Treatment of Relapsed or Refractory Chronic Lymphocytic Leukemia (R/R CLL): A Matching-Adjusted Indirect Comparison (MAIC) Mazyar Shadman 1 , Jennifer R Brown 2 , Rhys Williams 3 , Leyla Mohseninejad 4 , Keri Yang 3 , Pal Rakonczai 5 , Nicole Lamanna 6 , Sheng Xu 7 , Aileen Cleary Cohen 3 , Susan M. These side effects happen in between 1 and 10 out of every 100 people (between 1 and 10%). 5, 6 Available cancer trials have suggested that the risk of AF may be attenuated with newer BTK inhibitor therapy (eg, 30%-45% reduction with acalabrutinib [5%-10% high-grade] and zanubrutinib [3%-6% high-grade]). 04; and as of Efficacy of Zanubrutinib Versus Acalabrutinib in the Treatment of Relapsed or Refractory Chronic Lymphocytic Leukemia (R/R CLL): A Matching-Adjusted Indirect Comparison (MAIC) Mazyar Shadman 1 , Jennifer R Brown 2 , Rhys Williams 3 , Leyla Mohseninejad 4 , Keri Yang 3 , Pal Rakonczai 5 , Nicole Lamanna 6 , Sheng Xu 7 , Aileen Cleary Cohen 3 , Susan M. 1, 7, 11 In the phase 3 head-to-head ELEVATE-RR trial (NCT02477696), after a median study follow-up of 40. It’s been my go-to because it came in before zanubrutinib as an improvement over ibrutinib. 11. 7, 8 Acalabrutinib was approved by the FDA and European Medicines Agency for the treatment of patients with CLL/small lymphocytic lymphoma (SLL), and it was also approved by the FDA for patients with The discontinuation rate at 12 months was 22% for the weighted acalabrutinib cohort vs 31% for the weighted ibrutinib cohort (P = . idelalisib + rituximab or BR: 59% vs. Overall and exposure-adj Jennifer Woyach, MD: Similar to the head-to-head acalabrutinib-vs-ibrutinib study, this was set up to look at zanubrutinib vs ibrutinib in the relapse setting. 20 In the ASCEND trial the rate of grade ⩾3 diarrhea in patients receiving acalabrutinib was 1% – corroborating acalabrutinib less off-target inhibition of the EGFR kinase family. 8% v 4. Sensitivity analyses (excluding race and age) yielded consistent results. 3 The trials included in this NMA were the SEQUOIA study, the MABLE study, the CLL11 study, and the Zanubrutinib and acalabrutinib can be administered without food, as food did not result in significant effects on the area under the curve (AUC) Acalabrutinib vs. BREAKING NEWS. CMS Proposes Updates to ACA Health Plans. 84]; P=. 29; 95% CI: 0. 0% vs. S. 8% v 30. That doesn't distinguish them that much, but 1 thing that does distinguish zanubrutinib from both of them is its pharmacokinetic [PK] properties. 17%, HR: 0. 2958; 2L P<0. Objective: To compare efficacy of zanubrutinib vs acalabrutinib in patients with R/R MCL using a simulated treatment comparison (STC). Looking everything that's left of the dotted line favors acalabrutinib, everything that's right of the dotted line favors zanubrutinib. Acalabrutinib is more cost-effective compared with ibrutinib and zanubrutinib and improves health outcomes more in R/R MCL patients. 3. 2 out of 10 from a total of 27 ratings on Drugs. 1 hour), which effectively blocks the function of newly synthesized BTK protein as well as preexisting BTK irreversibly bound by zanubrutinib. 9 months, progression-free survival with acalabrutinib was noninferior to Phase 3 head-to-head comparisons between ibrutinib, acalabrutinib, zanubrutinib, and others are ongoing and just beginning to produce results. 53-0. 17 Indeed, in this analysis, the odds of any grade neutropenia were significantly higher The medicines had previously been compared to first-generation BTKi ibrutinib (Imbruvica) in the ELEVATE-RR trial (acalabrutinib vs ibrutinib) and the ALPINE study (zanubrutinib vs ibrutinib). 90; 95% CI, 0. “Zanubrutinib was also superior to ibrutinib in terms of progression-free survival,” he further reported. Five small molecule inhibitors have shown remarkable efficacy and have been approved to treat different types of hematological cancers, including ibrutinib, acalabrutinib, zanubrutinib, tirabrutinib, and orelabrutinib. Your doctor will tell you how to take it. Key Highlights From ASH 2023. Zanubrutinib in acalabrutinib-intolerant patients with B-cell malignancies. About half, or 327, received zanubrutinib, while 325 received ibrutinib. CLL Patients Recommended for Second 2024-25 COVID Vaccine. If the aforementioned comparison was statistically McCarthy H, Rule S, et Zanubrutinib. Choosing between acalabrutinib and zanubrutinib may rest on the amount of time a patient is willing to devote to In the ELEVATE TN trial, the rate of grade ⩾3 atrial fibrillation and hypertension was roughly 0. 9% vs 21. Like acalabrutinib, zanubrutinib is a newer type of BTK inhibitor, specifically designed to address ibrutinib’s shortcomings. 6% vs 20. Methods: Clinical trials of Abstract. Acalabrutinib with or without obinutuzumab significantly improved progression-free survival over obinutuzumab-chlorambucil chemoimmunotherapy, providing a chemotherapy-free treatment option with an acceptable side-effect profile that was consistent with previous studies. Zanubrutinib (Zanu) vs bendamustine + rituximab (BR) Findings from a matched adjusted indirect comparison (MAIC) of zanubrutinib (Brukinsa) vs acalabrutinib (Calquence) in patients with relapsed or refractory chronic lymphocytic leukemia (CLL) demonstrated that zanubrutinib had an advantage in progression-free survival (PFS) and complete response (CR) and potentially improved overall survival. Asked how clinicians might decide between the two acalabrutinib regimens, Brown said, “If you add the obinutuzumab, it does add more work for the patient,” and it adds more In summary, in this first directly comparative phase III trial of ibrutinib with acalabrutinib in CLL, acalabrutinib is noninferior in PFS and provides improved safety with A matching-adjusted indirect comparison (MAIC) analysis of zanubrutinib (Brukinsa) vs acalabrutinib (Calquence) in patients with relapsed/refractory chronic lymphocytic leukemia (CLL) demonstrated Efficacy of Zanubrutinib Versus Acalabrutinib in the Treatment of Relapsed or Refractory Chronic Lymphocytic Leukemia (R/R CLL): A Matching-Adjusted Indirect Comparison (MAIC) Mazyar Shadman 1 , Jennifer R Brown 2 , Rhys Williams 3 , Leyla Mohseninejad 4 , Keri Yang 3 , Pal Rakonczai 5 , Nicole Lamanna 6 , Sheng Xu 7 , Aileen Cleary Cohen 3 , Susan M. 3% vs 38%, as well as a higher proportion of patients who were Zanubrutinib Acalabrutinib + obinutuzumab vs zanubrutinib: HR: 0. 9 months, acalabrutinib ing acalabrutinib data from ASCEND with ibrutinib data from ALPINE, the INV-PFS for acalabrutinib post-matching was superior to the INV-PFS for ibrutinib (HR: 0. 3), which compared ibrutinib and zanubrutinib in patients with WM, significantly more (p ≤ 0. Methods: Patient-level data were pooled for R/R MCL patients treated with zanubrutinib from a phase I study (BGB-3111-AU-003, NCT02343120) and a phase II study (BGB-3111-206, NCT03206970). The phase 3 ASPEN study compared the efficacy and safety of ibrutinib, a first-generation BTK inhibitor, with zanubrutinib, a novel highly selective BTK inhibitor, in pati Zanubrutinib was associated with lower treatment switching rates vs acalabrutinib and ibrutinib in real-world chronic these rates were 9. We talked a bit about the frontline setting, and the relapsed/refractory setting is different. 27110. And mostly zanubrutinib lately because it doesn’t have some drug-drug interactions, so I don’t have to worry about dealing with PPIs Although, acalabrutinib does have a head-to-head comparison as does zanubrutinib. In other studies, no patients with MYD88 WT WM achieved a major Major bleeding rates were also lower with zanubrutinib (2. 05 [95% CI: 0. “Despite a similar [independent Data presented at the 2024 Society of Hematologic Oncology (SOHO) Annual Meeting showed that irrespective of whether patients were treated with a BTK inhibitor in the The study assessed the comparative efficacy of zanubrutinib vs acalabrutinib in patients with R/R MCL, in the absence of head-to-head clinical trials, using population In the SEQUOIA trial, fist-line zanubrutinib significantly improved PFS vs bendamustine plus rituximab in patients without del(17p), supporting the use of zanubrutinib in In distinction from acalabrutinib, zanubrutinib absorbance is not affected by co-administration with gastric acid-reducing agents, including proton-pump inhibitors. 96% of We used existing evidence from phase I/II clinical trials for second BTKi generation to evaluate the cost-effectiveness of ibrutinib vs acalabrutinib vs zanubrutinib in treating Newer generation of covalent BTKi, acalabrutinib and zanubrutinib, were designed with a greater selectivity for BTK with the premise of decreasing associated toxicities. 7 QALY savings compared with acalabrutinib for 1000 hypothetical patients. 9% vs 84. 3%). 1798) but not significant. A total of 73% of the acalabrutinib In addition, overall response rate (ORR) remained higher with zanubrutinib compared with ibrutinib (85. O'Brien 8 , Conclusions: With a median zanubrutinib exposure that was 6 months longer than the reported cumulative acalabrutinib exposure before discontinuation (11. 2020; 7 (2): e112- the indirect comparison estimate of zanubrutinib vs acalabrutinib is independent of the patient characteristics in the analysis and therefore consistent across the target populations. 53–1. Key Trial and Patient Characteristics at Baseline. 6%; 65% male; median age 66 years). Similar to acalabrutinib, zanubrutinib (formerly BGB-3111) also showed greater BTK selectivity and less off-target inhibition against alternative kinases including Acalabrutinib is a second-generation, selective, covalent BTKi 13 with demonstrated progression-free survival (PFS) and overall survival R/R cohort. 98). 05; no adjustment for multiplicity) ibrutinib versus zanubrutinib recipients experienced diarrhoea (32% vs 21%), muscle spasms (24% vs 10%), peripheral oedema (19% vs 9%), atrial fibrillation/flutter (15% vs 2%) and pneumonia (12% vs 2%), whereas significantly In a recent phase 2 trial, the combination of zanubrutinib, obinutuzumab, and venetoclax treatment in TN patients with TP53-mutated MCL demonstrated tolerable safety, high response rates, and high rates of Undetectable MRD (uMRD). In a pooled analysis of 89 patients with TP53 aberrations receiving ibrutinib in the frontline setting, the estimated 4-year PFS was 79%, and the median PFS had not been reached at a median follow-up of 50 months. Ibrutinib: Acalabrutinib. 4 vs 5. announced a new matching adjusted indirect comparison (MAIC) of the efficacy of Brukinsa (zanubrutinib) versus acalabrutinib in relapsed or refractory (R/R) chronic lymphocytic leukemia (CLL) based on data from the Phase Treatment with zanubrutinib (Brukinsa) maintained or improved response without an increase in acalabrutinib (Calquence) intolerance events in patients with previously treated B-cell malignancies Like zanubrutinib, acalabrutinib appears to have a better safety profile than ibrutinib, with a lower incidence of AF and hypertension [34, 68]. 3% of those on ibrutinib (HR, 0. NEWS. Patients do claim they have headaches pretty often with it, and I’ve always just told them, as At the sponsor-submitted price for zanubrutinib and the publicly listed prices for ibrutinib and acalabrutinib, zanubrutinib was less costly than ibrutinib and acalabrutinib. CONCLUSIONS • Zanubrutinib patients had significantly lower switching rates within 90 days. Zanubrutinib and acalabrutinib are approved for R/R MCL and demonstrated clinical benefits in separate single-arm trials. Zanubrutinib treatment resulted in £599,000 cost savings and 3. However, the Dr Tam noted that the investigator-assessed response in the zanubrutinib vs ibrutinib treatment groups was statistically significant (at data cutoff: 28. Now, a new analysis of data from a trial comparing the BTKis ibrutinib and acalabrutinib has revealed that the use of ibrutinib in previously treated CLL was associated with higher adverse event (AE) burden overall, specifically for atrial fibrillation Treatment with acalabrutinib (Calquence), in combination with obinutuzumab (Gazyva) or as a monotherapy, continued to induce superior progression-free survival (PFS) over obinutuzumab plus chlorambucil in treatment-naive patients with chronic lymphocytic leukemia (CLL), according to 6-year follow-up data from the ELEVATE-TN trial (NCT02475681) Sepsis was diagnosed in 6. 8%, respectively; P = . Table 1. 56 0. O’Brien8, Alessandra Tedeschi9, and Patients with CLL and SLL treated with either zanubrutinib or acalabrutinib were included, excluding those who received ibrutinib. org january 26, 2023 321 Zanubrutinib or Ibrutinib in CLL shop on CLL criteria and warranted treatment and if they had relapsed disease or disease that John Seymour, MD, discusses the safety of acalabrutinib vs ibrutinib in patients with chronic lymphocytic leukemia, Sonrotoclax Plus Zanubrutinib Generates Responses in Treatment-Naive CLL/SLL. 0 years at drug initiation; the ibrutinib cohort had a median age of 72. Paolo Ghia, MD, PhD, describes the various cohorts of the SEQUOIA study, expands on outcomes from a biomarker subgroup analysis with zanubrutinib vs bendamustine plus rituximab, and more. At WTP of $100,000, the cost-effectiveness acceptability curves showed the probabilities of acalabrutinib, zanubrutinib, and ibrutinib being cost-effective to be 50%, 34%, and 16%, respectively. Methods: In the unanchored MAIC, acalabrutinib IPD from ASCEND were weighted to match zanubrutinib baseline data from Importantly, when comparing data from patients treated with ibrutinib, acalabrutinib, zanubrutinib and tirabrutinib, the correlation of EGFR inhibition with rash is not obvious. Testing for the CR/VGPR superiority rate of zanubrutinib vs ibrutinib in patients with R/R WM was performed first. 2 Learn more about An indirect comparison of acalabrutinib with and without obinutuzumab versus zanubrutinib in treatment-naive CLL. Acalabrutinib is a more selective, covalent BTKi approved for CLL/small lymphocytic lymphoma with decreased off-target activity vs ibrutinib as demonstrated by in vitro studies. documented no statistically significant differences in PFS between acalabrutinib vs ibrutinib in combination with obinutuzumab across subgroups of patients with different levels of cytogenetic risk. Individual patie Acalabrutinib was approved in October 2017 for patients with R/R MCL Munir T, Shadman M, Robak T, Brown JR, Kahl BS, Ghia P, et al. 23,24 A consistent safety profile of zanubrutinib was observed in the present study; the long-term favorable tolerability of zanubrutinib was further established in this study with extended follow-up. All News FDA Briefs Oncology Icons Special Reports The Targeted Pulse Voices from the Field. 2. Proportion of pts receiving next line of therapy at 180 days was lower for zanu vs acala and ibru (1L P=0. Patients treated with zanubrutinib were also shown to be achieving numerically higher ORR than patients treated with acalabrutinib. Patients aged 18 or older with previously treated B-cell malignancies (chronic lymphocytic leukaemia, small lymphocytic lymphoma, mantle cell lymphoma, Waldenström macroglobulinaemia, or marginal zone lymphoma) who became intolerant of ibrutinib, More recently, interim analysis data from a second phase 3 study BGB-3111-305 (ALPINE) of zanubrutinib vs ibrutinib in patients with R/R CLL/SLL provided additional evidence to demonstrate clinical safety and efficacy superiority of zanubrutinib over ibrutinib (3. 0001. Conclusions: These results confirm that zanubrutinib continues to be more Leukemia - Efficacy and safety in a 4-year follow-up of the ELEVATE-TN study comparing acalabrutinib with or without obinutuzumab versus obinutuzumab plus chlorambucil Safety data from ELEVATE-RR revealed that the rate of discontinuation due to adverse effects (AEs) was lower for patients who received acalabrutinib (n = 266) compared In a cohort of 1,502 patients with CLL where 751 were treated with acalabrutinib and 751 were treated with zanubrutinib, there were 84 deaths (11. 4 months, respectively) Most patients (63%) did not experience any recurrence of their prior acalabrutinib-intolerance event Of the 40 acalabrutinib-intolerance events, 28 did not recur; Phase 2 Study of Zanubrutinib in Patients with Relapsed/Refractory B-Cell Malignancies Intolerant to Ibrutinib/Acalabrutinib Mazyar Shadman, MD MPH, Mazyar Shadman, MD MPH In the head-to-head ASPEN trial of zanubrutinib vs ibrutinib in patients with Waldenström macroglobulinemia (WM), zanubrutinib showed a lower rate of AEs Clinically, treating patients with R/R MCL with acalabrutinib was associated with an absolute survival gain of 0. 04; and as of In a pooled analysis of 89 patients with TP53 aberrations receiving ibrutinib in the frontline setting, the estimated 4-year PFS was 79%, and the median PFS had not been Acalabrutinib and zanubrutinib are second generation covalent BTKis that target the C481 BTK residue [Citation 10]. 2 Brown JR, et al Then zanubrutinib and acalabrutinib are second generation covalent inhibitors. 6% for acalabrutinib, Although head-to-head data for zanubrutinib vs acalabrutinib are lacking, findings from a meta-analysis presented at the 2023 EHA Congress by Steven Hwang, MD, of Mayo Clinic in Rochester, Minnesota, and colleagues, showed that both acalabrutinib and zanubrutinib were associated with improved AE profiles compared with ibrutinib. 72-1. 0%, respectively). O'Brien 8 , In a previously published MAIC of BRUKINSA versus acalabrutinib, 1 there were significant limitations that precluded a robust efficacy comparison, including the exclusion of data from the final Twenty-two acalabrutinib-intolerance events were reported in 13 pts, most commonly arthralgia (4), myalgia (3), headache (2), and hemorrhage (2). n engl j med 388;4 nejm. Key PointsTime-limited acalabrutinib, venetoclax, and obinutuzumab induced deep and ongoing remission in patients with relapsed/refractory CLL gatekeeper residue variation The median zanubrutinib exposure was 6 months longer than the reported cumulative acalabrutinib exposure before discontinuation (11. This is particularly important given the high incidence of infections Acalabrutinib had higher in vitro kinase selectivity than ibrutinib, zanubrutinib, and spebrutinib, and similar selectivity to tirabrutinib . All-grade atrial fibrillation/atrial flutter incidence was significantly lower with acalabrutinib versus ibrutinib (9. PMID: 37811799. New or Results: The NMA found a statistically significant improvement in PFS for zanubrutinib over acalabrutinib in high-risk patients and a trend towards improvement in OS, In the second trial, known as ALPINE, researchers compared zanubrutinib to a common CLL treatment of the same type, called ibrutinib (Imbruvica), that is known to have Preclinical studies confirmed greater specificity and better bioavailability of zanubrutinib compared with that of ibrutinib, which supported the initiation of clinical trials in The results of the ALPINE study and the ELEVATE RR study indicate that both of the more selective BTK inhibitors, zanubrutinib and acalabrutinib, demonstrate a favorable With the intention of minimising off-target adverse effects, new BTK inhibitors, such as zanubrutinib and acalabrutinib, have been developed and approved for the treatment of Zanubrutinib can be taken once a day or twice a day. O'Brien 8 , The study followed 652 patients from North America, Europe, and Asia-Pacific for a median of 42. 23–0. 57-1. 4 months vs 5. 23, 24 In a matching Zanubrutinib continues to demonstrate meaningful efficacy and favorable safety in patients with WM. Evidence on their comparative efficacy is lacking. We hypothesized that complete/sustained BTK occupancy may improve efficacy outcomes and increased BTK specificity may minimize off-target inhibition-related toxicities. 9%) were comparable between groups and median overall survival was not reached in either arm Regardless of line of therapy, switching rate at ≤60 days and 61-89 days was statistically significantly lower for pts receiving zanu vs acala and ibru (P<0. 2%, respectively; P =. 86; P =. 1% for zanubrutinib, 18. (Nasdaq: BGNE; HKEX: 06160; SSE: 688235), a global oncology company, Sustained Benefit of Zanubrutinib vs Ibrutinib in Patients With R/R CLL/SLL: Final Comparative Analysis of ALPINE. 9%), as were adverse events leading to treatment discontinuation (7. 5% in patients randomly assigned to the acalabrutinib arms. 21 The final analysis of the RESONATE trial Acalabrutinib (n=1238) Ibrutinib (n=1421) Zanubrutinib (n=157) Acalabrutinib (n=672) Ibrutinib (n=474) Zanubrutinib (n=107) 1L* 2L* 20. 6 The independent Incidence of atrial fibrillation/flutter was lower with zanubrutinib vs ibrutinib (7. 0 months, a sustained PFS benefit was seen with zanubrutinib vs ibrutinib, reducing the risk for disease progression by 32% (HR, 0. In the front line, we talked about BTK inhibitor vs chemotherapy mostly, and in relapsed/refractory, we have head-to-head data looking at that first-generation BTK ibrutinib vs the next-generation BTK inhibitors, acalabrutinib or zanubrutinib. 0%) and Richter transformations (3. Conclusions. November 21, 2024. Follow-up data from the ALPINE trial showed superior PFS and safety signals with zanubrutinib vs ibrutinib in this patient population. 55. 005; Table 2). ELEVATE-RR. BTK Inhibitors for R/R MCL. Zanubrutinib is much more specific for BTK than ibrutinib is. 20 In the same vein, Davids et al. A total of 73% of the acalabrutinib-intolerance events did not recur on zanubrutinib, corresponding to 62% of pts not experiencing a recurrence of any event. By Although head-to-head data for zanubrutinib vs acalabrutinib are lacking, findings from a meta-analysis presented at the 2023 EHA Congress by Steven Hwang, MD, of Mayo BASEL, Switzerland & BEIJING & CAMBRIDGE, Mass. 6% 10. bendamustine-rituximab arms) and infection (62. Although chemoimmunotherapy constituted the standard of care in earlier decades, Bruton tyrosine kinase (BTK) inhibitors (ibrutinib and acalabrutinib), BCL2 inhibitors (venetoclax), and combinations thereof are currently the cornerstone of CLL Similar to acalabrutinib, the initial clinical experiences with zanubrutinib reported a favorable AE profile compared with that of ibrutinib. 8% vs 13. 1 hour), which effectively After matching patient characteristics, improved progression-free survival (PFS) was observed with acalabrutinib plus obinutuzumab versus zanubrutinib monotherapy (HR, An economic analysis of Zanubrutinib versus Acalabrutinib and associated QoL benefits in AE management in patients with B-cell malignancies. 001: ASCEND : 3: 109 vs. 5% of patients treated with acalabrutinib and 21. Bruton tyrosine kinase (BTK) inhibition is an effective treatment approach for patients with Waldenström macroglobulinemia (WM). 873). These data support the use of acalabrutinib in combination with obinutuzumab or alone as a Tolerability vs Other BTKis while using BRUKINSA® (zanubrutinib) BTK inhibitor for treatment of CLL/SLL. Acalabrutinib, however, did have a higher incidence of headache (34. 3% with ibrutinib at 40. More about Calquence (acalabrutinib) More about Zanubrutinib Ratings & Reviews: Calquence has an average rating of 9. Epub 2023 Oct 9. Zanubrutinib is an irreversible, covalent-binding BTK inhibitor that was approved for treating Waldenström macroglobulinemia (WM) in 2021 and for CLL in 2023. The primary outcome of interest was major cardiovascular adverse events, composed of heart failure, myocardial infarction, and An increase in the odds of some AEs is expected when comparing a combination regimen with a monotherapy. Preclinical studies confirmed BeiGene, Ltd. 14; Table 2). 9% of patients treated with zanubrutinib received next-line therapy by day 180 compared with 24. 4 mo, respectively), 17 pts (63%) did not experience Zanubrutinib (BGB-3111), a potent, irreversible next-generation BTKi, is more selective for BTK inhibition and exhibits less off-target kinase activity than ibrutinib. Lancet Haematol. doi: 10. 0%) or death which In the acalabrutinib monotherapy vs zanubrutinib monotherapy comparison, the odds of any-grade hypertension were significantly lower with acalabrutinib monotherapy (OR, More about Brukinsa (zanubrutinib) More about Calquence (acalabrutinib) Ratings & Reviews: Brukinsa has an average rating of 8. FDA-approved BTK inhibitors (BTKis), Zanubrutinib Versus Acalabrutinib in B-cell Malignancies: An Adverse Event-Based Economic Analysis Talha 1Munir, Vincent Levy, 2 Leyla Mohseninejad, 3 Tushar Srivastava, 4 Anurag acalabrutinib, and acalabrutinib's major metabolite (M27) by kinase profiling • Of the 370 kinases tested, zanubrutinib, ibrutinib, acalabrutinib, and M27 demonstrated > 50% inhibition of 7, 17, More about Calquence (acalabrutinib) More about Zanubrutinib Ratings & Reviews: Calquence has an average rating of 9. 5% and 2. 6% (n=2,249) received ibrutinib and 14. Approximately 640 patients will be randomized 1:1 to receive either 3 cycles of zanubrutinib monotherapy (320 mg total daily dose, orally), followed by zanubrutinib + sonrotoclax for 12 cycles, or standard ven + obi treatment for 12 cycles. 04/10/2024 The second-generation Bruton tyrosine kinase inhibitors acalabrutinib (acala) and zanubrutinib (zanu) have not been compared with each other in a head-to-head randomized The risk of having AEs was broadly comparable between acalabrutinib and zanubrutinib, except for having an SAE, any grade and grade ≥3 hypertension, any grade Although life-saving, BTK inhibitors are associated with an up to 3-5 fold increase in AF and other (eg, VA) events when compared with patients not exposed to BTK inhibitor therapy. The study provides evidence to support the superiority of zanubrutinib over acalabrutinib in R/R MCL. Two experts compare experiences and data concerning use of ibrutinib, acalabrutinib, and zanubrutinib in B-cell lymphomas. 2 mo vs 3. Authors Adam S Results From January 2018 through February 2021, 2,509 patients were identified and included in the analysis. Am J Hematol. ALPINE. 0001) (Table). 28 Long-term follow-up of doublet vs triplet BTK inhibitor–based therapies is needed to assess the balance between durability of Talha Munir, MBChB, PhD, discusses an adverse effect–based economic analysis of zanubrutinib vs acalabrutinib in patients with B-cell malignancies. 0% for zanubrutinib vs. 001), according to the abstract. 5% <60 days 61-89 days * P <. 90, Learn more about An indirect comparison of acalabrutinib with and without obinutuzumab versus zanubrutinib in treatment-naive CLL. 4%), while use of zanubrutinib (80. The ELEVATE-RR trial and ASPEN trials both found a lower incidence of AF with acalabrutinib or zanubrutinib compared with those who received ibrutinib 29,30 In an open-label, randomised, prospective phase III study a next-generation, irreversible Bruton's tyrosine kinase (BTK) inhibitor, acalabrutinib demonstrated similar efficacy and improved safety with fewer atrial fibrillation events and discontinuations because of adverse events than ibrutinib in patients with previously treated chronic lymphocytic leukaemia (CLL). DISCUSSION • Ibrutinib Acalabrutinib Zanubrutinib Canadian Approval CLL, MCL CLL, MCL CLL, MCL Selectivity Dosing 420mg PO daily (CLL, WM) 560mg PO daily (MCL ,MZL) 100mg PO BID 160mg PO BID or 320mg PO daily 21 22. The findings further confirm the safety and efficacy of acalabrutinib for treating CLL / SLL. and lower proportion of patients receiving next line This ongoing, phase 2, multicentre, open-label, single-arm study was done in 20 centres in the USA. Ibrutinib: One is acalabrutinib- zanubrutinib. After matching patient characteristics, improved progression-free survival (PFS) was observed with acalabrutinib plus obinutuzumab versus zanubrutinib monotherapy (HR, 0. If the aforementioned comparison was statistically significant, Acalabrutinib monotherapy in patients with Waldenström macroglobulinemia: a single-arm, multicentre, phase 2 study. The twice daily dosing of zanubrutinib achieves 8-fold higher plasma drug exposure than ibrutinib and a longer half-life than acalabrutinib (4 vs. “Despite a similar [independent review committee] progression-free survival, survival non-statistically favored acalabrutinib with 10 fewer deaths,” Byrd said. We conducted an open-label, randomized, noninferiority, phase 3 trial to compare Aca vs Ib in patients (pts) with chronic lymphocytic leukemia (CLL). “Zanubrutinib was also superior to ibrutinib in terms of progression-free survival,” he further However, the Dr Tam noted that the investigator-assessed response in the zanubrutinib vs ibrutinib treatment groups was statistically significant (at data cutoff: 28. Methods: A health economic model was developed to determine In a multinational, phase 3, head-to-head trial, ibrutinib, a Bruton’s tyrosine kinase (BTK) inhibitor, was compared with zanubrutinib, a BTK inhibitor with greater specificity, as treatment for Results: After matching, the effective sample size of acala was 99 (66. 4% 15. In the acalabrutinib trial, it’s in relapsed refractory high risk patients, so those are with CLL with a 17p deletion or an 11q deletion, who are relapsed are randomly assigned. 9% and 89. 3%) than ibrutinib. 25 0. 8 mo, respectively), disease was controlled in 13 (93%) of 14 efficacy-evaluable pts treated with zanubrutinib, and 11 (65%) did not experience any recurrence of their prior acalabrutinib All-grade bleeding was less frequent with acalabrutinib (38%) than with ibrutinib (51. Investigators identified similar progression-free survival (PFS) associated with acalabrutinib (Calquence) and zanubrutinib (Brukinsa) in the treatment of patients with relapsed/refractory chronic lymphocytic leukemia (CLL), according to findings from an unanchored matching-adjusted indirect comparison of data from the phase 3 ASCEND (NCT02970318) Zanubrutinib (Brukinsa) vs acalabrutinib (Calquence) demonstrated a significant improvement in progression-free survival (PFS) and complete response (CR) in patients with chronic lymphocytic leukemia (CLL), which was analyzed using a matching-indirect comparison (MAIC) analysis, presented at the 28th International Congress of Hematologic Malignancies. In the head-to-head ELEVATE-RR clinical trial, rates of discontinuation among R/R CLL patients with del(11q) or del(17p) were 14. The BTKis approved for R/R MCL (ibrutinib, acalabrutinib, and zanubrutinib) covalently and irreversibly bind to cysteine 481 within the ATP At the sponsor-submitted price for zanubrutinib and the publicly listed prices for ibrutinib and acalabrutinib, zanubrutinib was less costly than ibrutinib and acalabrutinib. Acalabrutinib is also more specific for BTK. Some AEs that are particular to acalabrutinib vs zanubrutinib may sway our decisions one way or the other. 6%) and acalabrutinib (68. 21 These findings In the SEQUOIA trial, fist-line zanubrutinib significantly improved PFS vs bendamustine plus rituximab in patients without del(17p), supporting the use of zanubrutinib in untreated CLL and SLL. 119: Determining Optimal CLL / SLL Therapy: Ibrutinib, Acalabrutinib and Zanubrutinib . For example, zanubrutinib binds BTK proteins with greater precision, remains bound to more BTK proteins for longer, and persists at high concentrations in the body during treatment, the study authors noted. 48 years (~6 months) and a quality-adjusted survival gain of 0. 74 0 6 12 18 24 30 36 42 48 54 60 66 72 Time from randomization (months) Acalabrutinib monotherapy pre-matching Acalabrutinib monotherapy post-matching Zanubrutinib Acalabrutinib monotherapy vs zanubrutinib: HR: 0. 35 The first head-to-head comparison of zanubrutinib vs ibrutinib was conducted in patients with WM (ASPEN study). 9% and Zanubrutinib significantly improved progression-free survival versus bendamustine–rituximab, with an acceptable safety profile consistent with previous studies. idelalisib + rituximab While acalabrutinib and zanubrutinib have been directly compared with ibrutinib in clinical trials in relapsed/refractory CLL, these BTKi have never been directly compared as first The twice daily dosing of zanubrutinib achieves 8-fold higher plasma drug exposure than ibrutinib and a longer half-life than acalabrutinib (4 vs. Population-adjusted indirect treatment comparisons (ITC) can be conducted to estimate relative treatment effects between different BTKis that were not studied head-to-head, while adjusting for between-trial differences in important patient characteristics. Zanubrutinib was originally developed by applying a structure- activity strategy to enhance the specificity as well as enzymatic and pharmacokinetic properties. 7% with acalabrutinib vs 21. 96% of At the sponsor-submitted price for zanubrutinib and the publicly listed prices for ibrutinib and acalabrutinib, zanubrutinib was less costly than ibrutinib and acalabrutinib. 99% for zanubrutinib vs Zanubrutinib and acalabrutinib are approved for R/R MCL and demonstrated clinical benefits in separate single-arm trials. The advent of targeted therapies has transformed the treatment landscape of chronic lymphocytic leukaemia (CLL). Randomization will be stratified by age (<65 vs ≥65 years) and IGHV and del(17p)/TP53 mutation status. 9% and While zanubrutinib had relatively smaller sample size and shorter follow-up, patients were more likely to remain on first-line treatment at 6 and 12 months in the zanubrutinib group. The MAIC hazard ratio (HR) for INV PFS is similar for acala vs zanu (HR 0. Aims: We used unanchored matching-adjusted indirect comparison (MAIC) to compare the efficacy and safety of acalabrutinib vs zanubrutinib using individual patient data (IPD) from ASCEND and published aggregate data from ALPINE. We further characterize AEs of acalabrutinib and ibrutinib via post hoc analysis. --(BUSINESS WIRE)-- BeiGene, Ltd. 1002/ajh. Poster presented at: American Society of Hematology (ASH) Annual Meeting and Exposition; December 9-12, 2023. There are there slightly different trials. Of these patients, 89. 77; 95% CI, 0. 5 1 2 4 8 Two recent phase 3, randomized, head-to-head studies in patients with WM and R/R CLL/SLL demonstrated advantages of zanubrutinib vs ibrutinib in safety and tolerability. Introduction: Next-generation Bruton tyrosine kinase inhibitors (BTKis) acalabrutinib (acala) and zanubrutinib (zanu) were compared with the standard of care BTKi ibrutinib in relapsed/refractory chronic lymphocytic leukemia (RR CLL) in the head-to-head randomized clinical trials (RCTs) ELEVATE-RR and ALPINE, respectively. 41, 95% CI: 0. 0%); no cardiac deaths were reported with zanubrutinib vs six cardiac deaths with Background: The clinical management of chronic lymphocytic leukemia (CLL) and mantle cell lymphoma (MCL) continues to evolve. 2% 13. 27110 Calquence (acalabrutinib) vs Brukinsa (zanubrutinib) Calquence (acalabrutinib) and Brukinsa (zanubrutinib) are both Bruton's tyrosine kinase (BTK) inhibitors used to treat certain types of B-cell malignancies, such as mantle cell lymphoma and chronic lymphocytic leukemia. Next-generation BTK inhibitors (eg, acalabrutinib, zanubrutinib) appear to have fewer adverse cardiac effects than ibrutinib. After a median follow-up of 39. Brown explained that compared with ibrutinib and acalabrutinib, zanubrutinib has higher concentration ratios and thus offers more complete inhibition of BTK; also, unlike the others, A comprehensive discussion on a matching-adjusted indirect comparison study investigating the efficacy of zanubrutinib vs acalabrutinib in relapsed/refractory chronic lymphocytic leukemia. 2 For the TN subgroup, due to a lack of head-to-head evidence comparing zanubrutinib to ibrutinib and to acalabrutinib, the sponsor submitted an NMA and an MAIC comparing their relative efficacy. 1% 7. Those are the main differences. 5% of patients receiving acalabrutinib vs 11. Although there is no head-to-head comparison between second-generation BTKis, acalabrutinib demonstrated a lower odds ratio (OR) for several AEs. Again, showing the same factors, hemorrhage of any grade, hypertension of any grade or high grade. The way that both acalabrutinib and ibrutinib work is by irreversibly binding to and destroying the cancerous B lymphocytes. 11,25 Furthermore, compared Acalabrutinib, however, did have a higher incidence of headache (34. Acalabrutinib’s increased selectivity means that the risk of off-target cells, or noncancerous cells, is much lower than in ibrutinib, which thus results in a lower risk of adverse effects. 4% v 16. Zanubrutinib and acalabrutinib can be administered without food, as food did not result in significant effects on the area under the curve (AUC) for these drugs [19, 20], whereas Weighing Continuous Therapy Options for CLL. Knowledge Test - MAIC Case Study: Zanubrutinib vs. 75% of Findings from an unanchored matching-adjusted indirect comparison of data from the phase 3 ASCEND (NCT02970318) and ALPINE (NCT03734016) trials showed that Zanubrutinib was associated with significantly fewer hospitalizations than ibrutinib (45% vs. 0011). 1% vs. 9%) tended to be in the relapsed or refractory setting. Hemorrhage (45. The results are similar to those seen in larger phase 3 clinical trials, which have In contrast to ibrutinib, acalabrutinib and zanubrutinib which are nonreversible, covalent BTK inhibitors, pirtobrutinib is a reversible non-covalent BTK inhibitor with low nM Newer generation of covalent BTKi, acalabrutinib and zanubrutinib, were designed with a greater selectivity for BTK with the premise of decreasing associated toxicities. 1% (n=353) received acalabrutinib across all lines of therapy. Conclusion: This STC demonstrated that zanubrutinib had significantly better PFS and OS vs acalabrutinib in the treatment of patients with R/R MCL He added that throughout the key patient subgroups, zanubrutinib was favored. Acalabrutinib virtually does not inhibit EGFR and was shown to have at least 10 times lower affinity for EGFR when compared to ibrutinib, A matching-adjusted indirect comparison of acalabrutinib versus zanubrutinib in relapsed or refractory chronic lymphocytic leukemia Am J Hematol. 04/10/2024 In the ASPEN trial (Sect. found no statistically significant differences in PFS and OS between acalabrutinib and ibrutinib. It could be seen from the structure that Zanubrutinib retains the electrophilic groups' acrylamide and diphenyl ether groups of Ibrutinib, but does not contain the pyrimidine ring Zanubrutinib may be used in the treatment of patients who are TN or r/r. 0001, both 1L and 2L) (Table). 56%). The efficacy and safety of acalabrutinib plus obinutuzumab and acalabrutinib monotherapy vs zanubrutinib in patients with treatment-naive chronic lymphocytic leukemia/small lymphocytic lymphoma without del(17p) were compared using an unanchored matching-adjusted indirect comparison. There were less adverse events leading to dose reduction in the acalabrutinib arm. 4% vs 17. To identify the best partner for venetoclax, 2 studies will compare the doublets of venetoclax plus a BTKi or obinutuzumab (NCT04608318, the CLL17 study for ibrutinib vs VO vs IV; NCT05057494, the A matching-adjusted indirect comparison of acalabrutinib versus zanubrutinib in relapsed or refractory chronic lymphocytic leukemia. BTK inhibitors acalabrutinib (Calquence) and zanubrutinib (Brukinsa) are next-generation treatments for chronic lymphocytic leukemia (CLL), and they’ve shown promise for progression-free survival. 02); among other selected secondary end points, grade 3 or higher infections (30. 1% vs 17. com. 7 out of 10 from a total of 24 ratings on Drugs. Pharmacokinetics and pharmacodynamics. 12- and 24-month INV PFS are shown below. 34 Zanubrutinib also does not Notably, after matching, the acalabrutinib arm had a lower proportion of patients below 65 years of age than in the ibrutinib arm (33. 1% of patients treated with ibrutinib. 5 months. 40; P = . Ibrutinib was more often used in the front-line setting (68. EP: 10. 6% for acalabrutinib, and 29. 1 Conclusion: With a median zanubrutinib exposure that was longer than the reported cumulative acalabrutinib exposure before discontinuation (9. Head-to-head ALPINE interim results: superior ORR and improved safety of zanubrutinib versus ibrutinib in r/r CLL. In the first-line setting, 13. Conclusion: Zanubrutinib was associated with a 27% lower risk of major This study aims to evaluate costs and impacts on quality of life (QoL) for zanu vs acala using their AE profiles. 41; P < 0. (82. 21 The ELEVATE-TN and SEQUOIA studies showed similar efficacy with acalabrutinib and zanubrutinib in this high-risk population; the 5-year PFS in both Zanubrutinib (BGB-3111) is a highly selective second-generation irreversible BTK inhibitor developed by BeiGene company, which was approved by U. 36 Although ASPEN failed to meet its primary end point of superior complete and very good How it applies to choosing zanubrutinib over acalabrutinib [Calquence] is a little bit less clear; we're not going to have that head-to-head trial. The 12-month landmark event-free rates for zanubrutinib vs ibrutinib were 94. 36 years (~4 months) over treatment with ibrutinib but at an additional cost of was higher with zanubrutinib vs acalabrutinib (odds ratio, 2. Acalabrutinib and zanubrutinib monotherapy displayed better real-world safety and efficacy in chronic lymphocytic leukemia and small lymphocytic lymphoma compared with ibrutinib. 96]; p=0. 11,12 In a phase I/II zanubrutinib study (BGB-3111-AU-003) in patients with CLL/SLL (82%; 101 of 123 relapsed/refractory), zanubrutinib demonstrated complete and sustained BTK occupancy in Efficacy of Zanubrutinib Versus Acalabrutinib in the Treatment of Relapsed or Refractory Chronic Lymphocytic Leukemia: A Matching-Adjusted Indirect Comparison Mazyar Shadman1, Jennifer R Brown2, Rhys Williams3, Leyla Mohseninejad4, Keri Yang3, Pal Rakonczai5, Nicole Lamanna6, Sheng Xu7, Aileen Cleary Cohen3, Susan M. 91, 95% CI: 0. 68; 95% CI, 0. 185%) with acalabrutinib Along with the combination of venetoclax and obinutuzumab, the BTK inhibitor–based regimens of zanubrutinib monotherapy and acalabrutinib plus obinutuzumab Testing for the CR/VGPR superiority rate of zanubrutinib vs ibrutinib in patients with R/R WM was performed first. EP: 8. 0 years. 2% for zanubrutinib), this exposure is approximately eightfold higher than that observed with ibrutinib 560 mg daily. Economic Burden Associated With BTK Inhibitor Use. 9% vs 3. 5, 6 In ELEVATE-RR, which A matching-adjusted indirect comparison of acalabrutinib versus zanubrutinib in relapsed or refractory chronic lymphocytic leukemia. Notably, after matching, the acalabrutinib arm had a lower proportion of patients below 65 years of age than in the ibrutinib arm (33. 05 [95% CI, 0. After a median follow-up of 40. 46 for zanubrutinib vs 42 acalabrutinib at 1 μM in MDCK-MDR1 assay) Background: Increased selectivity of the Bruton tyrosine kinase inhibitor (BTKi) acalabrutinib (Aca) vs ibrutinib (Ib) may improve tolerability. 0%, respectively (HR = 0. 60-0. Skip to content. 41; 36-month PFS rate, 95% vs 84%); however, acalabrutinib plus obinutuzumab therapy was associated with increased adverse event rates, particularly neutropenia and arthralgia. @article{Kittai2023AMI, title={A matching‐adjusted indirect comparison of acalabrutinib versus zanubrutinib in relapsed or refractory chronic lymphocytic leukemia}, Zanubrutinib and acalabrutinib can be administered without food, as food did not result in significant effects on the area under the curve (AUC) Acalabrutinib vs. In the second-line setting, these rates were 9. 72-5. 125 0. 6/17/2024 12 Are patients with CLL living longer with new therapies? Ghia et al Hemasphere 2024 23 A phase 3 study incorporating acalabrutinib in place of ibrutinib has completed accrual (NCT03836261: acalabrutinib plus venetoclax vs AVO vs FCR). Fleming: I would probably choose acalabrutinib. 9 months follow Approximately 1-fifth of patients on zanubrutinib or acalabrutinib had been switched from ibrutinib. They are more highly selective for BTK than ibrutinib which Knowledge Test - MAIC Case Study: Zanubrutinib vs. The acalabrutinib vs ibrutinib trial showed (zanubrutinib vs ibrutinib) and the ELEVATE-RR trial (acalabrutinib vs ibrutinib). Kingsley EC, et al. Both of those trials focused on CLL patients with relapsed/refractory CLL and showed that the second-generation BTKis had much fewer side effects compared to The efficacy and safety of acalabrutinib plus obinutuzumab and acalabrutinib monotherapy vs zanubrutinib in patients with treatment-naive chronic lymphocytic leukemia/small lymphocytic lymphoma without del(17p) were compared using an unanchored matching-adjusted indirect comparison. The data have a much shorter follow-up. Those taking acalabrutinib had a lower risk than those taking zanubrutinib of having: A serious AE; Any grade and ≥ 3-grade hypertension; Any grade hemorrhage; An AE leading to dose reduction; Conclusions: Progression-free survival was similar for both drugs, Zanubrutinib is the only BTK inhibitor to demonstrate progression-free survival superiority vs ibrutinib in relapsed or refractory CLL, as observed in the ALPINE trial. 0%; P = . Acalabrutinib had a numerically lower rate of discontinuation vs ibrutinib in the unweighted analysis, but the results were not statistically significant (HR, 0. In biochemical assays, ibrutinib inhibited Src family kinases, whereas acalabrutinib and tirabrutinib did not inhibit EGF-induced EGF receptor activation or T-cell receptor-mediated T-cell activation in cellular assays at physiologically relevant . Zanubrutinib. EP: 9. The ALPINE trial assessed the use of Stroke occurred in 20 zanubrutinib and 19 acalabrutinib patients (RR, 1. Food and Drug Administration (FDA) for the treatment of CLL or small lymphocytic lymphoma as front-line therapy and in relapsed or Twenty-two acalabrutinib-intolerance events were reported in 13 pts, most commonly arthralgia (4), myalgia (3), headache (2), and hemorrhage (2). FDA in 2019 with a Brukinsa trade name 40. Purpose: Zanubrutinib is a potent, irreversible next-generation Bruton tyrosine kinase (BTK) inhibitor designed to maximize BTK occupancy and minimize off-target kinase inhibition. 2% for ibrutinib. Inverse propensity score weighting In contrast to ibrutinib, acalabrutinib and zanubrutinib which are nonreversible, covalent BTK inhibitors, pirtobrutinib is a reversible non-covalent BTK inhibitor with low nM potency against both wild type and C481 mutated BTK, 300-fold selectivity for BTK relative to 98% of other kinases [Citation 31]. 60; 95% CI: Flowers turned to the phase 3 ELEVATE-RR trial (NCT02477696), which assessed ibrutinib vs acalabrutinib in patients with relapsed/refractory CLL. The first-in-class agent, ibrutinib, has created a new era of chemotherapy-free treatment of B cell malignancies. The acalabrutinib cohort had a median age of 73. Acalabrutinib. Approved in 2014, Bruton tyrosine kinase inhibitors (BTKis) have revolutionized the treatment of chronic lymphocytic leukemia (CLL). 7, 8 Acalabrutinib was After adjusting for plasma protein binding (94. BTK inhibitors are rapidly absorbed after oral administration with a median time to the peak concentration (T max) of 1–2 h []. 2% 21. 4. However, differences in these ELEVATE-RR demonstrated noninferior progression-free survival and lower incidence of key adverse events (AEs) with acalabrutinib vs ibrutinib in previously treated chronic lymphocytic leukemia. The patients were divided into two groups based on the line of zanubrutinib: the second-line and the later-line group. 20–0. Molica et al. 0007). 3% vs 38%, as well as a higher proportion Progression-free survival (PFS) appeared to improve with zanubrutinib (Brukinsa) vs bendamustine plus rituximab (Rituxan) among subgroups of patients with chronic Acalabrutinib was approved by the U. The efficacy and safety of acalabrutinib plus obinutuzumab and acalabrutinib monotherapy vs zanubrutinib in patients with treatment-naive chronic lymphocytic The ASCEND trial looked at acalabrutinib vs investigator’s choice of either rituximab (Rituxan) or bendamustine (Bendeka) plus rituximab in patients with relapsed/refractory CLL. 1 zanubrutinib was associated with significantly greater PFS and OS vs acalabrutinib. 2%, respectively) and cough (28. 20 For example, higher rates of neutropenia and arthralgia were observed with acalabrutinib plus obinutuzumab vs acalabrutinib monotherapy in the ELEVATE-TN RCT. He added that throughout the key patient subgroups, zanubrutinib was favored. rvbync lpuh ueaoplw ujbtvse sbnkxm fjzpsy avk ndktj eqqq vsryis