On June 14, 2024 Amgen (NASDAQ:AMGN) reported the U.S. Food and Drug Administration (FDA) has approved BLINCYTO (blinatumomab) for the treatment of adult and pediatric patients one month or older with CD19-positive Philadelphia chromosome-negative B-cell precursor acute lymphoblastic leukemia (B-ALL) in the consolidation phase, regardless of measurable residual disease (MRD) status (Press release, Amgen, JUN 14, 2024, View Source [SID1234644328]).

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"B-ALL is an aggressive blood cancer with enduring high unmet need. BLINCYTO has helped thousands of patients with B-ALL over the last 10 years. Today’s approval in the frontline consolidation phase, regardless of MRD status, allows us to reach more patients than ever with this transformative, first-in-class Bispecific T-cell Engager (BiTE) therapy," said Jay Bradner, M.D., executive vice president, Research and Development, and chief scientific officer at Amgen.

The approval marks the third indication for BLINCYTO and is based primarily on the Phase 3 E1910 clinical trial led by ECOG-ACRIN Cancer Research Group that studied patients with newly diagnosed Philadelphia chromosome-negative B-ALL receiving postinduction consolidation treatment, which aims to deepen remission to achieve durable responses. Study results demonstrated that BLINCYTO added to multiphase consolidation chemotherapy showed superior overall survival (OS) versus chemotherapy alone. The 3-year OS was 84.8% in the BLINCYTO plus chemotherapy arm (n=112) and 69% in the chemotherapy arm (n=112), with the hazard ratio for OS of 0.42. With a median follow-up of 4.5 years, the 5-year OS was 82.4% in the BLINCYTO plus chemotherapy arm and 62.5% in the chemotherapy arm.

"In the E1910 study, blinatumomab reduced risk of death and showed a remarkable improvement in overall survival," said Selina M. Luger, M.D., professor of hematology-oncology at the University of Pennsylvania’s Perelman School of Medicine and Abramson Cancer Center, chair of the ECOG-ACRIN Leukemia Committee and an investigator on the study. "This approval redefines the standard of care for patients with B-ALL and provides them with a more effective treatment option than standard chemotherapy alone."

"The risk of B-ALL recurrence after the initial phase of treatment is relatively high, making this approval for patients noteworthy," said E. Anders Kolb, M.D., president and chief executive officer of The Leukemia & Lymphoma Society. "B-ALL is the most common type of ALL and having another effective option available earlier in a patient’s treatment journey is critical for clinicians who are working to give these patients more time with their loved ones."

The E1910 study was designed and conducted independently from industry. ECOG-ACRIN sponsored the trial with public funding from the National Cancer Institute (NCI), part of the National Institutes of Health (NIH). Other NCI-funded network groups took part in the study. In addition, Amgen provided BLINCYTO and support through an NCI Cooperative Research and Development Agreement.

About Acute Lymphoblastic Leukemia (ALL)
ALL, also known as acute lymphoblastic leukemia, is a fast-growing type of blood cancer that develops in the bone marrow and can sometimes spread to other parts of the body, including the lymph nodes, liver, spleen, and central nervous system. ALL is a rare disease, with 6,540 new cases diagnosed in the U.S. in 2023 affecting both children and adults.1 B-ALL begins in immature cells that would normally develop into B-cell lymphocytes, which are white blood cells that grow in bone marrow.2,3 B-ALL is the most common type of ALL, constituting approximately 75% of cases in adults.4

About BLINCYTO (blinatumomab)
BLINCYTO is the first globally approved BiTE immuno-oncology therapy that targets CD19 surface antigens on B cells. BiTE molecules fight cancer by helping the body’s immune system detect and target malignant cells by engaging T cells (a type of white blood cell capable of killing other cells perceived as threats) to cancer cells. By bringing T cells near cancer cells, the T cells can inject toxins and trigger cancer cell death (apoptosis). BiTE immuno-oncology therapies are currently being investigated for their potential to treat a wide variety of cancers.

BLINCYTO was granted breakthrough therapy and Priority Review designations by the U.S. FDA and is approved in the U.S. for the treatment of:

Adult and pediatric patients one month or older with CD19-positive Philadelphia chromosome-negative B-ALL during the consolidation phase of multiphase therapy.
CD19-positive B-ALL in first or second complete remission with MRD greater than or equal to 0.1% in adults and pediatric patients one month or older.
Relapsed or refractory CD19-positive B-ALL in adults and pediatric patients one month or older.
In the European Union (EU), BLINCYTO is indicated as monotherapy for the treatment of:

Adults with Philadelphia chromosome-negative CD19-positive relapsed or refractory B-ALL. Patients with Philadelphia chromosome-positive B-ALL should have failed treatment with at least two tyrosine kinase inhibitors (TKIs) and have no alternative treatment options.
Adults with Philadelphia chromosome-negative CD19-positive B-ALL in first or second complete remission with MRD greater than or equal to 0.1%.
Pediatric patients aged 1 year or older with Philadelphia chromosome-negative CD19-positive B-ALL which is refractory or in relapse after receiving at least two prior therapies or in relapse after receiving prior allogeneic hematopoietic stem cell transplantation.
Pediatric patients aged 1 year or older with high-risk first relapsed Philadelphia chromosome-negative CD19-positive B-ALL as part of the consolidation therapy.
INDICATIONS

BLINCYTO (blinatumomab) is indicated for the treatment of CD19-positive B-cell precursor acute lymphoblastic leukemia (ALL) in adult and pediatric patients one month and older with:

Philadelphia chromosome-negative disease in the consolidation phase of multiphase chemotherapy.
Minimal residual disease (MRD) greater than or equal to 0.1% in first or second complete remission.
Relapsed or refractory disease.
BLINCYTO IMPORTANT SAFETY INFORMATION

WARNING: CYTOKINE RELEASE SYNDROME and NEUROLOGICAL TOXICITIES including IMMUNE EFFECTOR CELL-ASSOCIATED NEUROTOXICITY SYNDROME

Cytokine Release Syndrome (CRS), which may be life-threatening or fatal, occurred in patients receiving BLINCYTO. Interrupt or discontinue BLINCYTO and treat with corticosteroids as recommended.
Neurological toxicities, including immune effector cell-associated neurotoxicity syndrome (ICANS) which may be severe, life-threatening, or fatal, occurred in patients receiving BLINCYTO. Interrupt or discontinue BLINCYTO as recommended.
Contraindications

BLINCYTO is contraindicated in patients with a known hypersensitivity to blinatumomab or to any component of the product formulation.

Warnings and Precautions

Cytokine Release Syndrome (CRS): CRS, which may be life-threatening or fatal, occurred in patients receiving BLINCYTO. The median time to onset of CRS is 2 days after the start of infusion and the median time to resolution of CRS was 5 days among cases that resolved. Closely monitor and advise patients to contact their healthcare professional for signs and symptoms of serious adverse events such as fever, headache, nausea, asthenia, hypotension, increased alanine aminotransferase (ALT), increased aspartate aminotransferase (AST), increased total bilirubin (TBILI), and disseminated intravascular coagulation (DIC). The manifestations of CRS after treatment with BLINCYTO overlap with those of infusion reactions, capillary leak syndrome (CLS), and hemophagocytic histiocytosis/macrophage activation syndrome (MAS). Using all of these terms to define CRS in clinical trials of BLINCYTO, CRS was reported in 15% of patients with R/R ALL, in 7% of patients with MRD-positive ALL, and in 16% of patients receiving BLINCYTO cycles in the consolidation phase of therapy. If severe CRS occurs, interrupt BLINCYTO until CRS resolves. Discontinue BLINCYTO permanently if life-threatening CRS occurs. Administer corticosteroids for severe or life-threatening CRS.

Neurological Toxicities, including Immune Effector Cell-Associated Neurotoxicity Syndrome: BLINCYTO can cause serious or life-threatening neurologic toxicity, including ICANS. The incidence of neurologic toxicities in clinical trials was approximately 65%. The median time to the first event was within the first 2 weeks of BLINCYTO treatment. The most common (≥ 10%) manifestations of neurological toxicity were headache and tremor. Grade 3 or higher neurological toxicities occurred in approximately 13% of patients, including encephalopathy, convulsions, speech disorders, disturbances in consciousness, confusion and disorientation, and coordination and balance disorders. Manifestations of neurological toxicity included cranial nerve disorders. The majority of neurologic toxicities resolved following interruption of BLINCYTO, but some resulted in treatment discontinuation.

The incidence of signs and symptoms consistent with ICANS in clinical trials was 7.5%. The onset of ICANS can be concurrent with CRS, following resolution of CRS, or in the absence of CRS. There is limited experience with BLINCYTO in patients with active ALL in the central nervous system (CNS) or a history of neurologic events. Patients with a history or presence of clinically relevant CNS pathology were excluded from clinical studies. Patients with Down Syndrome over the age of 10 years may have a higher risk of seizures with BLINCYTO therapy.

Monitor patients for signs and symptoms of neurological toxicities, including ICANS, and interrupt or discontinue BLINCYTO as outlined in the PI. Advise outpatients to contact their healthcare professional if they develop signs or symptoms of neurological toxicities.

Infections: Approximately 25% of patients receiving BLINCYTO in clinical trials experienced serious infections such as sepsis, pneumonia, bacteremia, opportunistic infections, and catheter-site infections, some of which were life-threatening or fatal. Administer prophylactic antibiotics and employ surveillance testing as appropriate during treatment. Monitor patients for signs or symptoms of infection and treat appropriately, including interruption or discontinuation of BLINCYTO as needed.

Tumor Lysis Syndrome (TLS), which may be life-threatening or fatal, has been observed. Preventive measures, including pretreatment nontoxic cytoreduction and on-treatment hydration, should be used during BLINCYTO treatment. Monitor patients for signs and symptoms of TLS and interrupt or discontinue BLINCYTO as needed to manage these events.

Neutropenia and Febrile Neutropenia, including life-threatening cases, have been observed. Monitor appropriate laboratory parameters (including, but not limited to, white blood cell count and absolute neutrophil count) during BLINCYTO infusion and interrupt BLINCYTO if prolonged neutropenia occurs.

Effects on Ability to Drive and Use Machines: Due to the possibility of neurological events, including seizures and ICANS, patients receiving BLINCYTO are at risk for loss of consciousness, and should be advised against driving and engaging in hazardous occupations or activities such as operating heavy or potentially dangerous machinery while BLINCYTO is being administered.

Elevated Liver Enzymes: Transient elevations in liver enzymes have been associated with BLINCYTO treatment with a median time to onset of 3 days. In patients receiving BLINCYTO, although the majority of these events were observed in the setting of CRS, some cases of elevated liver enzymes were observed outside the setting of CRS, with a median time to onset of 19 days. Grade 3 or greater elevations in liver enzymes occurred in approximately 7% of patients outside the setting of CRS and resulted in treatment discontinuation in less than 1% of patients. Monitor ALT, AST, gamma-glutamyl transferase, and total blood bilirubin prior to the start of and during BLINCYTO treatment. BLINCYTO treatment should be interrupted if transaminases rise to > 5 times the upper limit of normal (ULN) or if total bilirubin rises to > 3 times ULN.

Pancreatitis: Fatal pancreatitis has been reported in patients receiving BLINCYTO in combination with dexamethasone in clinical trials and the post-marketing setting. Evaluate patients who develop signs and symptoms of pancreatitis and interrupt or discontinue BLINCYTO and dexamethasone as needed.

Leukoencephalopathy: Although the clinical significance is unknown, cranial magnetic resonance imaging (MRI) changes showing leukoencephalopathy have been observed in patients receiving BLINCYTO, especially in patients previously treated with cranial irradiation and antileukemic chemotherapy.

Preparation and administration errors have occurred with BLINCYTO treatment. Follow instructions for preparation (including admixing) and administration in the PI strictly to minimize medication errors (including underdose and overdose).

Immunization: Vaccination with live virus vaccines is not recommended for at least 2 weeks prior to the start of BLINCYTO treatment, during treatment, and until immune recovery following last cycle of BLINCYTO.

Benzyl Alcohol Toxicity in Neonates: Serious adverse reactions, including fatal reactions and the "gasping syndrome," have been reported in very low birth weight (VLBW) neonates born weighing less than 1500 g, and early preterm neonates (infants born less than 34 weeks gestational age) who received intravenous drugs containing benzyl alcohol as a preservative. Early preterm VLBW neonates may be more likely to develop these reactions, because they may be less able to metabolize benzyl alcohol.

Use the preservative-free preparations of BLINCYTO where possible in neonates. When prescribing BLINCYTO (with preservative) for neonatal patients, consider the combined daily metabolic load of benzyl alcohol from all sources including BLINCYTO (with preservative), other products containing benzyl alcohol or other excipients (e.g., ethanol, propylene glycol) which compete with benzyl alcohol for the same metabolic pathway.

Monitor neonatal patients receiving BLINCYTO (with preservative) for new or worsening metabolic acidosis. The minimum amount of benzyl alcohol at which serious adverse reactions may occur in neonates is not known. The BLINCYTO 7-Day bag (with preservative) contains 7.4 mg of benzyl alcohol per mL.

Embryo-Fetal Toxicity: Based on its mechanism of action, BLINCYTO may cause fetal harm when administered to a pregnant woman. Advise pregnant women of the potential risk to the fetus. Advise females of reproductive potential to use effective contraception during treatment with BLINCYTO and for 48 hours after the last dose.
Adverse Reactions

The safety of BLINCYTO in adult and pediatric patients one month and older with MRD-positive B-cell precursor ALL (n=137), relapsed or refractory B-cell precursor ALL (n=267), and Philadelphia chromosome-negative B cell precursor ALL in consolidation (n=165) was evaluated in clinical studies. The most common adverse reactions (≥ 20%) to BLINCYTO in this pooled population were pyrexia, infusion-related reactions, headache, infection, musculoskeletal pain, neutropenia, nausea, anemia, thrombocytopenia, and diarrhea.
Dosage and Administration Guidelines

BLINCYTO is administered as a continuous intravenous infusion at a constant flow rate using an infusion pump which should be programmable, lockable, non-elastomeric, and have an alarm.
It is very important that the instructions for preparation (including admixing) and administration provided in the full Prescribing Information are strictly followed to minimize medication errors (including underdose and overdose).
Please see BLINCYTO full Prescribing Information, including BOXED WARNINGS.

About BiTE Technology
Bispecific T-cell Engager (BiTE) technology is a targeted immuno-oncology platform that is designed to engage patient’s own T cells to any tumor-specific antigen, activating the cytotoxic potential of T cells to eliminate detectable cancer. The BiTE immuno-oncology platform has the potential to treat different tumor types through tumor-specific antigens. The BiTE platform has a goal of leading to off-the-shelf solutions, which have the potential to make innovative T cell treatment available to all providers when their patients need it. Amgen is advancing multiple BiTE molecules across a broad range of hematologic malignancies and solid tumors, further investigating BiTE technology with the goal of enhancing patient experience and therapeutic potential. To learn more about BiTE technology, visit View Source

On June 14, 2024 enGene Holdings Inc. (Nasdaq: ENGN, "enGene" or the "Company"), a clinical-stage genetic medicines company whose non-viral, intravesical lead product candidate, EG-70, is in a pivotal study for BCG-unresponsive high-risk non-muscle invasive bladder cancer (NMIBC), reported its financial results for the second quarter ended April 30, 2024, and provided a business update (Press release, enGene, JUN 14, 2024, View Source [SID1234644349]).

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"Our $200 million private placement in February positioned us well to execute our primary strategy of broadly developing EG-70 to be a patient- and practice-friendly option across a multitude of potential bladder cancer indications. Correspondingly, our planned initial expansion of the LEGEND study will include a cohort focused on enrollment of patients with high-risk, BCG-unresponsive papillary-only NMIBC, a disease with persistent unmet need for which EG-70 may be well-suited," said Jason Hanson, Chief Executive Officer of enGene. "Furthermore, we plan to provide the interim data for the LEGEND BCG-unresponsive cohort by the end of September 2024. We believe the design of EG-70, with its ease-of-use and non-viral profile, positions it well to seamlessly slot into the standard of care, with the goal of becoming a practice-changing product that does not require a change in practice for urologists."

Anticipated Milestones and Strategic Corporate Updates

Release of interim data from LEGEND Cohort 1: The Company expects to release interim data from the LEGEND study’s BCG-unresponsive cohort by the end of September, comprised of responses from approximately 20 patients focused on the three- and six-month time points. Study enrollment remains ongoing, and based on current projections, enGene expects to file a Biologics License Application (BLA) for EG-70 in mid-2026.

Commitment to expanding the clinical development of EG-70 within the bladder: Building on the design of EG-70 to have category-leading ease of use, scalable manufacturing process, and low cost-of-goods, the Company plans to explore additional applications of EG-70 within the bladder by expanding the LEGEND study to include a third cohort targeting high-risk BCG-unresponsive papillary-only NMIBC patients and modifying the second cohort (previously, the BCG-naïve cohort) to include BCG-exposed patients. Collectively, these potential indications represent an expansion into several areas of persistent unmet medical need with substantial patient populations. These clinical development plans include:

Papillary-only LEGEND expansion: The Company plans to expand LEGEND to enroll a third cohort of patients with BCG-unresponsive, papillary-only Ta/T1 disease. This cohort, whose target enrollment is 70-100 patients, is estimated to begin enrollment in the fourth quarter of 2024.
Modification of the second cohort of LEGEND study to separately analyze responses between BCG-naïve patients and BCG-exposed patients: In anticipation of this planned cohort modification and expected corresponding engagement with FDA, enrollment has been temporarily paused in this second cohort, with enrollment in both groups expected to resume in the fourth quarter of 2024.
As a result of the prioritization of these potential new indications in bladder cancer, the Company has deprioritized pre-clinical development of EG-i08 for cystic fibrosis and has paused further activities on that program.

Key leadership hires and board additions: In May 2024, enGene announced the election of Paul Hastings and Wouter Joustra as new members of its Board of Directors at the Company’s 2024 annual meeting of shareholders. Lota Zoth was also re-elected to the Board. Each will serve a three-year term expiring at the 2027 annual meeting of shareholders. enGene’s Board is comprised of seven members including Richard Glickman (Chairman), Gerald Brunk, Jasper Bos, and enGene CEO, Jason Hanson.

In April 2024, the Company announced that Raj Pruthi MD MHA FACS joined the Company as SVP, Urologic Oncology and Clinical Development. Dr. Pruthi joined enGene from Johnson & Johnson Innovative Medicine, where he was most recently the Global Medical Affairs Leader, Bladder Cancer and Senior Medical Director, Oncology (Global – Prostate and Bladder Cancer).

Second Quarter 2024 Financial Results

Cash and cash equivalents, as of April 30, 2024, were $264.8 million. The Company expects that its existing cash and cash equivalents will fund operating expenses, debt obligations and capital expenditures into 2027.

Three Months ended April 30, 2024
Total operating expenses were $17.3 million for the three months ended April 30, 2024, compared to $4.7 million for the three months ended April 30, 2023. Research and development expenses increased by $6.6 million, mainly due to increasing manufacturing and clinical costs related to our pivotal EG-70 study. General and administrative expenses increased by $5.9 million, primarily driven by headcount costs and professional fees such as legal, accounting and audit as the Company scales its general and administrative function to support the operation of a public company.

For the three months ended April 30, 2024, net loss attributable to common shareholders was approximately $15.0 million, or $0.38 per share, compared to approximately $6.5 million, or $9.30 per share, for the same period for the three months ended April 30, 2023. The increase in net loss is mainly attributed to the increase in operating expenses partially offset by net interest income earned during the period.

On June 14, 2024 Aptose Biosciences Inc. ("Aptose" or the "Company") (NASDAQ: APTO, TSX: APS), a clinical-stage precision oncology company developing highly differentiated oral targeted agents to treat hematologic malignancies, reported a clinical poster presentation and a preclinical e-poster at the European Hematology Association (EHA) (Free EHA Whitepaper) 2024 Hybrid Congress in Madrid, Spain (Press release, Aptose Biosciences, JUN 14, 2024, View Source [SID1234644329]).

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Tuspetinib (TUS) is being developed as a TUS + venetoclax (VEN) + hypomethylating agent (HMA) triple drug combination (or TUS+VEN+HMA triplet) as frontline therapy for newly diagnosed AML patients. Aptose’s poster presentation illustrates the safety and breadth of activity of TUS monotherapy and the TUS+VEN doublet combination in relapsed or refractory (R/R) AML patients from the APTIVATE Phase 1/2 trial and supports the launch of the TUS+VEN+HMA (using azacitidine, AZA, as the HMA) triplet frontline therapy in newly diagnosed AML patients. Tuspetinib, a convenient once daily oral agent that potently targets SYK, FLT3, mutated KIT, JAK1/2, and RSK2 kinases, avoids many typical toxicity concerns observed with other agents. In the APTIVATE trial, TUS achieved broad activity across AML patients with a diversity of adverse genetics as a single agent and in combination with venetoclax in a very ill and heavily pre-treated AML population. Blast reductions and objective responses were observed in patients with prior-VEN, prior-FLT3 inhibitor (FLT3i) and prior-HSCT therapies, those with highly adverse genetics – including mutations in TP53 and RAS genes, and those with mutated or unmutated (wildtype) FLT3 genes.

"Our APTIVATE trial of tuspetinib as a monotherapy and in combination treatment with venetoclax in a very ill AML patient population, has yielded excellent, consistent safety and demonstrated clinical activity across a broad range of AML – including many with highly adverse genetic mutations," said Rafael Bejar, M.D., Ph.D., Corresponding Author and Chief Medical Officer of Aptose. "The AML treatment paradigm is quickly shifting to combination therapy for newly diagnosed AML patients, but current triplet therapies in development are limited by toxicities and are aimed at narrow subpopulations, leaving them unable to treat the larger AML population. Tuspetinib, with demonstrated broad activity and favorable safety/tolerability profile, appears to be an ideal third agent to add to a venetoclax and hypomethylating agent regimen. We and our clinical investigators are eager to initiate dosing of the TUS+VEN+AZA triplet study."

TITLE: Safety and Efficacy of Tuspetinib as Monotherapy and Combined with Venetoclax in a Phase 1/2 Trial of Patients with Relapsed or Refractory (R/R) Acute Myeloid Leukemia (AML) (EHA ID # P557)

CONCLUSIONS

Extensive dose exploration with TUS (93 patients) and TUS+VEN (79 patients) in highly treatment experienced R/R AML patients (prior VEN, FLT3i, HMA, chemotherapy, HSCT)
TUS monotherapy
Complete remissions achieved at 40, 80, 120, and 160 mg with no DLT
42% CRc and 50% ORR was observed in VEN naïve and FLT3-mutation harboring patients.
Responses achieved in patients harboring highly adverse genetics (TP53MUT, RASMUT, other)
TUS+VEN Doublet
Remains safe and well tolerated (40mg TUS + 400mg VEN | 80mg TUS + 400mg VEN)
Achieves bone marrow blast reductions and responses among diverse R/R AML patients with
adverse mutations and prior failure of VEN
TUS targets known VEN resistance mechanisms in vitro and is clinically active in both FLT3MUT & FLT3WT R/R AML populations even after prior VEN exposure.
AML 1L UNMET NEED AND TUS+VEN+HMA TRIPLET

Significant Unmet Medical Need in Frontline Newly Diagnosed AML

Progress made with VEN+HMA in 1L therapy but 1/3 do not respond and median OS <15 months with <25% alive at 3-years.
Response rates and OS need improvement, especially in adverse genetic subgroups
Emergence of VEN resistance via RAS/MAPK, TP53, and FLT3 clonal expansion, among other mechanisms, compromises salvage therapies in R/R setting
A 3rd agent is needed to boost responses with VEN+HMA standard of care therapy
TUS is Ideal 3rd Agent for Addition to VEN+AZA to Treat Newly Diagnosed AML

TUS has excellent safety alone and in combination with VEN when co-administered
TUS has broad activity across genetic subgroups including TP53, RAS/MAPK, & FLT3 mutants
TUS mechanism may minimize drug resistance to VEN via inhibition of key AML kinases
TUS can be administered with or without food allowing co-administration with VEN
Preliminary PK data suggest no clinically meaningful interaction between TUS and VEN requiring dose modification for co-administration.
In addition, a separate preclinical abstract was published as an e-poster publication at EHA (Free EHA Whitepaper):

TITLE: Tuspetinib Retains Nanomolar Potency Against AML Cells Engineered to Express the NRAS G12D Mutation or Selected for Resistance to Venetoclax (EHA ePoster ID # P1756).

The study demonstrated that TUS targets known venetoclax (VEN) resistance mechanisms, retaining nanomolar potency against AML cells engineered to express the NRAS-G12D mutation or selected for resistance to VEN, and in combination with VEN, could prevent emergence of resistance to both agents. TUS resistant cells showed hypersensitivity to VEN such that treatment with both drugs could also interfere with the emergence of TUS resistance.

To see the full poster presentations, please visit Aptose’s website:
View Source

On June 14, 2024 Vertex Pharmaceuticals Incorporated (Nasdaq: VRTX) reported longer-term data for CASGEVY (exagamglogene autotemcel [exa-cel]) from global clinical trials in people with severe sickle cell disease (SCD) or transfusion-dependent beta thalassemia (TDT) (Press release, Vertex Pharmaceuticals, JUN 14, 2024, View Source [SID1234644350]). The results, presented at the annual European Hematology Association (EHA) (Free EHA Whitepaper) Congress, confirm the transformative, consistent and durable clinical benefits of CASGEVY over time. CASGEVY is the first and only approved CRISPR-based gene-editing therapy.

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The data being presented are from more than 100 patients (46 SCD; 56 TDT) treated with exa-cel in clinical trials, with the longest follow-up now extending more than 5 years. The efficacy results are consistent with the previously reported primary and key secondary endpoints analyses from these exa-cel studies and continue to demonstrate transformative clinical benefit with durable and stable levels of fetal hemoglobin (HbF) and allelic editing.

"The transformative benefit seen in patients with sickle cell disease in the trial is impressive given the significant and cumulative burden of disease faced by people living with this blood disorder," said Haydar Frangoul, M.D., M.S., Medical Director of Pediatric Hematology and Oncology at Sarah Cannon Research Institute and HCA Healthcare’s TriStar Centennial Children’s Hospital. "I am eager to offer this therapy and the opportunity of a potential functional cure to my eligible patients."

"The comprehensive data set presented today for adult and adolescent TDT patients adds to the growing body of evidence for CASGEVY, and it is important to now ensure the availability of this innovative treatment to patients in the real world as soon as possible," said Franco Locatelli, M.D., Ph.D., Professor of Pediatrics at the Catholic University of the Sacred Heart of Rome, Director of the Department of Pediatric Hematology and Oncology at Bambino Gesù Children’s Hospital. "With the longest follow up now more than five years, alongside stable editing and sustained fetal hemoglobin levels, I have conviction in the durable benefit to the patients treated with CASGEVY."

New data presented from CASGEVY pivotal trials

In SCD 36/39 (92.3%) evaluable patients (those with at least 16 months of follow-up) were free from vaso-occlusive crises (VOCs) for at least 12 consecutive months (VF12), consistent with the previously reported primary endpoint data. Mean duration of VOC-free was 27.9 months, with a maximum of 54.8 months.
38/39 (97.4%) patients with at least 16 months of follow-up were free from hospitalizations related to VOCs for at least 12 consecutive months (HF12), consistent with the previously reported key secondary endpoint data.
In TDT 49/52 (94.2%) evaluable patients (those with at least 16 months of follow-up) were transfusion-independent for at least 12 consecutive months with a mean weighted hemoglobin of at least 9 g/dL (TI12), consistent with the previously reported primary endpoint data. Mean duration of transfusion independence was 31.0 months, with a maximum of 59.4 months.
All TDT patients dosed with at least 16 months of follow up are transfusion free.
Two of the three patients who did not achieve TI12 in CLIMB-111 achieved TI12 in the long-term follow-up study, CLIMB-131, and have been transfusion independent for over one year. The third has been transfusion free for 3.4 months.
Both SCD and TDT patients reported sustained and clinically meaningful improvements in their quality of life, including physical, emotional, social/family and functional well-being, and overall health status.
In both SCD and TDT patients, edited levels of BCL11A alleles were stable over time in bone marrow and peripheral blood indicating successful editing in the long-term hematopoietic stem cells. All patients engrafted neutrophils and platelets after exa-cel infusion. The safety profile of exa-cel was generally consistent with myeloablative conditioning with busulfan and autologous hematopoietic stem cell transplant.

These longer-term data for CASGEVY from the CLIMB clinical trials will be shared as outlined below:

Abstracts S273 and S274 will be oral presentations entitled "Exagamglogene Autotemcel For Severe Sickle Cell Disease," and "Exagamglogene Autotemcel For Transfusion-Dependent Beta-Thalassemia," on Sunday, June 16 at 12:15 CEST and 12:30 CEST, respectively.
Abstracts P1493 and P1525 will be poster presentations entitled "Health-Related Quality Of Life Improvements After Exagamglogene Autotemcel In Patients With Severe Sickle Cell Disease," and "Health-Related Quality Of Life Improvements After Exagamglogene Autotemcel In Patients With Transfusion-Dependent Βeta-Thalassemia," on Friday, June 14 at 18:00 CEST.
These presentations will include updated pivotal trial data from patients treated with CASGEVY in CLIMB-111 and CLIMB-121 and followed in CLIMB-131.
Vertex will also share five health economics abstracts at the EHA (Free EHA Whitepaper) Congress.

Abstract P1483 is entitled "Adherence, Treatment Use, and Clinical Outcomes in Patients With Sickle Cell Disease With Recurrent Vaso-Occlusive Crises Treated With L-Glutamine, Voxelotor, or Crizanlizumab in the United States."
Abstract P1506 is entitled "Mortality and Clinical Complications Among Patients with Sickle Cell Disease With Recurrent VOCs in Canada."
Abstract P1507 is entitled "Treatment Utilization and Clinical Complications in Patients with Sickle Cell Disease Receiving Frequent Red Blood Cell Transfusions in the United States."
Abstract P2191 is entitled "Clinical Complications and Treatment Use Among Patients With Sickle Cell Disease With Recurrent Vaso-Occlusive Crises in the Netherlands."
Abstract PB3248 is entitled "Clinical Complications Among Patients With Transfusion-Dependent Beta-Thalassemia in the Netherlands."
About Sickle Cell Disease (SCD)

SCD is a debilitating, progressive, life shortening genetic disease. SCD patients report health-related quality of life scores well below the general population and significant health care resource utilization. SCD affects the red blood cells, which are essential for carrying oxygen to all organs and tissues of the body. SCD causes severe pain, organ damage and shortened life span due to misshapen or "sickled" red blood cells. The clinical hallmark of SCD is vaso-occlusive crises (VOCs), which are caused by blockages of blood vessels by sickled red blood cells and result in severe and debilitating pain that can happen anywhere in the body at any time. SCD requires lifelong treatment and significant use of health care resources, and ultimately results in reduced life expectancy, decreased quality of life and reduced lifetime earnings and productivity. In Europe, the mean age of death for patients living with SCD is around 40 years. Stem cell transplant from a matched donor is a potentially curative option but is only available to a small fraction of people living with SCD because of the lack of available donors.

About Transfusion-Dependent Beta Thalassemia (TDT)

TDT is a serious, life-threatening genetic disease. TDT patients report health-related quality of life scores below the general population and significant health care resource utilization. TDT requires frequent blood transfusions and iron chelation therapy throughout a person’s life. Due to anemia, patients living with TDT may experience fatigue and shortness of breath, and infants may develop failure to thrive, jaundice and feeding problems. Complications of TDT can also include an enlarged spleen, liver and/or heart, misshapen bones and delayed puberty. TDT requires lifelong treatment and significant use of health care resources, and ultimately results in reduced life expectancy, decreased quality of life and reduced lifetime earnings and productivity. In Europe, the mean age of death for patients living with TDT is 50-55 years. Stem cell transplant from a matched donor is a potentially curative option but is only available to a small fraction of people living with TDT because of the lack of available donors.

About CASGEVY (exagamglogene autotemcel [exa-cel])

CASGEVY is a non-viral, ex vivo CRISPR/Cas9 gene-edited cell therapy for eligible patients with SCD or TDT, in which a patient’s own hematopoietic stem and progenitor cells are edited at the erythroid specific enhancer region of the BCL11A gene through a precise double-strand break. This edit results in the production of high levels of fetal hemoglobin (HbF; hemoglobin F) in red blood cells. HbF is the form of the oxygen-carrying hemoglobin that is naturally present during fetal development, which then switches to the adult form of hemoglobin after birth.

CASGEVY has been shown to reduce or eliminate VOCs for patients with SCD and transfusion requirements for patients with TDT.

CASGEVY is approved for certain indications in multiple jurisdictions for eligible patients.

About the CLIMB Studies

The ongoing Phase 1/2/3 open-label trials, CLIMB-111 and CLIMB-121, are designed to assess the safety and efficacy of a single dose of CASGEVY in patients ages 12 to 35 years with TDT or with SCD, characterized by recurrent VOCs, respectively. The trials are now closed for enrollment. Patients will be followed for approximately two years after CASGEVY infusion. Each patient will be asked to participate in the ongoing long-term, open-label trial, CLIMB-131. CLIMB-131 is designed to evaluate the safety and efficacy of CASGEVY in patients who received CASGEVY in other CLIMB studies. The trial is designed to follow patients for up to 15 years after CASGEVY infusion.

U.S. INDICATIONS AND IMPORTANT SAFETY INFORMATION FOR CASGEVY (exagamglogene autotemcel)

WHAT IS CASGEVY?

CASGEVY is a one-time therapy used to treat people aged 12 years and older with:

sickle cell disease (SCD) who have frequent vaso-occlusive crises or VOCs
beta thalassemia (β-thalassemia) who need regular blood transfusions
CASGEVY is made specifically for each patient, using the patient’s own edited blood stem cells, and increases the production of a special type of hemoglobin called hemoglobin F (fetal hemoglobin or HbF). Having more HbF increases overall hemoglobin levels and has been shown to improve the production and function of red blood cells. This can eliminate VOCs in people with sickle cell disease and eliminate the need for regular blood transfusions in people with beta thalassemia.

IMPORTANT SAFETY INFORMATION

What is the most important information I should know about CASGEVY?

After treatment with CASGEVY, you will have fewer blood cells for a while until CASGEVY takes hold (engrafts) into your bone marrow. This includes low levels of platelets (cells that usually help the blood to clot) and white blood cells (cells that usually fight infections). Your doctor will monitor this and give you treatment as required. The doctor will tell you when blood cell levels return to safe levels.

Tell your healthcare provider right away if you experience any of the following, which could be signs of low levels of platelet cells:
severe headache
abnormal bruising
prolonged bleeding
bleeding without injury such as nosebleeds; bleeding from gums; blood in your urine, stool, or vomit; or coughing up blood
Tell your healthcare provider right away if you experience any of the following, which could be signs of low levels of white blood cells:
fever
chills
infections
You may experience side effects associated with other medicines administered as part of the treatment regimen for CASGEVY. Talk to your physician regarding those possible side effects. Your healthcare provider may give you other medicines to treat your side effects.

How will I receive CASGEVY?

Your healthcare provider will give you other medicines, including a conditioning medicine, as part of your treatment with CASGEVY. It’s important to talk to your healthcare provider about the risks and benefits of all medicines involved in your treatment.

After receiving the conditioning medicine, it may not be possible for you to become pregnant or father a child. You should discuss options for fertility preservation with your healthcare provider before treatment.

STEP 1: Before CASGEVY treatment, a doctor will give you mobilization medicine(s). This medicine moves blood stem cells from your bone marrow into the blood stream. The blood stem cells are then collected in a machine that separates the different blood cells (this is called apheresis). This entire process may happen more than once. Each time, it can take up to one week.

During this step rescue cells are also collected and stored at the hospital. These are your existing blood stem cells and are kept untreated just in case there is a problem in the treatment process. If CASGEVY cannot be given after the conditioning medicine, or if the modified blood stem cells do not take hold (engraft) in the body, these rescue cells will be given back to you. If you are given rescue cells, you will not have any treatment benefit from CASGEVY.

STEP 2: After they are collected, your blood stem cells will be sent to the manufacturing site where they are used to make CASGEVY. It may take up to 6 months from the time your cells are collected to manufacture and test CASGEVY before it is sent back to your healthcare provider.

STEP 3: Shortly before your stem cell transplant, your healthcare provider will give you a conditioning medicine for a few days in hospital. This will prepare you for treatment by clearing cells from the bone marrow, so they can be replaced with the modified cells in CASGEVY. After you are given this medicine, your blood cell levels will fall to very low levels. You will stay in the hospital for this step and remain in the hospital until after the infusion with CASGEVY.

STEP 4: One or more vials of CASGEVY will be given into a vein (intravenous infusion) over a short period of time.

After the CASGEVY infusion, you will stay in hospital so that your healthcare provider can closely monitor your recovery. This can take 4-6 weeks, but times can vary. Your healthcare provider will decide when you can go home.

What should I avoid after receiving CASGEVY?

Do not donate blood, organs, tissues, or cells at any time in the future
What are the possible or reasonably likely side effects of CASGEVY?

The most common side effects of CASGEVY include:

Low levels of platelet cells, which may reduce the ability of blood to clot and may cause bleeding
Low levels of white blood cells, which may make you more susceptible to infection
Your healthcare provider will test your blood to check for low levels of blood cells (including platelets and white blood cells). Tell your healthcare provider right away if you get any of the following symptoms:

fever
chills
infections
severe headache
abnormal bruising
prolonged bleeding
bleeding without injury such as nosebleeds; bleeding from gums; blood in your urine, stool, or vomit; or coughing up blood
These are not all the possible side effects of CASGEVY. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

General information about the safe and effective use of CASGEVY

Talk to your healthcare provider about any health concerns.

Please see full Prescribing Information including Patient Information for CASGEVY.

On June 14, 2024 BeiGene, Ltd. (NASDAQ: BGNE; HKEX: 06160; SSE: 688235), a global oncology company, reported the presentation of new data from the SEQUOIA study of BRUKINSA (zanubrutinib) at the European Hematology Association (EHA) (Free EHA Whitepaper) 2024 Hybrid Congress (EHA2024) in Madrid, Spain in an oral session (Abstract S160) (Press release, BeiGene, JUN 14, 2024, View Source [SID1234644331]). The presentation will feature data from arm D of SEQUOIA evaluating BRUKINSA in combination with venetoclax in treatment-naïve (TN) patients with high-risk chronic lymphocytic leukemia (CLL) and/or small lymphocytic lymphoma (SLL) with del(17p) and/or TP53 mutation. The preliminary data demonstrate that in the 65 response-evaluable patients treated with the combination, the overall response rate (ORR) was 100%, and the rate of complete response (CR) plus CR with incomplete hematopoietic recovery (CRi) was 48%. The safety profile of the combination is consistent with that of the treatment components, and no new safety signals were seen.

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"Patients with untreated CLL with del(17p) or TP53 mutations often face a poor prognosis, even in the front-line setting, so there is a critical need to better understand how this patient population responds to combination approaches," said Alessandra Tedeschi, M.D., Ph.D., consultant in hematology and Medical Director of the Department of Hematology at the Niguarda Cancer Center in Milan, Italy. "This arm of the SEQUOIA study showed that zanubrutinib in combination with a BCL2 inhibitor demonstrates promising efficacy and tolerability for high-risk CLL patients, providing important information about the clinical profile of this regimen."

Overall, 66 patients with centrally assessed del(17p) and/or TP53 mutation were enrolled in this arm of the SEQUOIA study. Patients received BRUKINSA at 160 mg twice daily for three months, followed by combination treatment of BRUKINSA at the same dose and venetoclax with a ramp-up dosing to 400 mg once daily for 12 to 24 cycles until progressive disease, unacceptable toxicity or confirmed undetectable minimal residual disease (MRD). In the 65 response-evaluable patients, ORR was 100%; the rate of CR+CRi was 48% (CR=46%; CRi=2%). Undetectable MRD was achieved in 59% of patients in ≥1 peripheral blood sample and with a median study follow up of 31.6 months. Median progression-free survival (PFS) was not reached; 12- and 24-month PFS estimates were 95% and 94%, respectively.

"SEQUOIA has shown that BRUKINSA is a highly effective monotherapy treatment for TN CLL patients, including those with high-risk markers like del(17p) and/or TP53 mutation. With one of the largest pools of high-risk patients of any published study to date, SEQUOIA arm D demonstrates how BCL2 inhibitor therapies can complement BRUKINSA as a backbone therapy to achieve deep clinical response even in this patient population," said Mehrdad Mobasher, M.D., M.P.H., Chief Medical Officer, Hematology at BeiGene. "We look forward to evaluating the potential for time-limited therapy with longer follow-up and incorporating these findings into our development program for our investigational next-generation BCL2 inhibitor sonrotoclax."

The safety profile of BRUKINSA plus venetoclax was consistent with results of prior studies of both medicines, and no new safety signals were identified. In total, 97% of patients experienced ≥1 treatment emergent adverse effect (TEAE). The most common all-grade non-hematologic TEAEs were infections (71%), COVID-19 (55%), diarrhea (39%), nausea (30%) and contusion (29%). Grade ≥3 non-hematologic TEAEs occurred in 44% of patients; the most common were infections (15%), diarrhea (9%), hypertension (8%) and second primary malignancies (8%). The most common all grade and grade ≥3 hematologic toxicity was neutropenia (22% and 17%, respectively). The proportion of patients at high risk for tumor lysis syndrome (TLS) decreased 91% from 35% at screening to 3% after three cycles of lead-in BRUKINSA, and no TLS was reported.

About SEQUOIA

SEQUOIA (NCT03336333) is a randomized, multicenter, global Phase 3 trial designed to evaluate the efficacy and safety of BRUKINSA in patients with TN CLL or SLL. The trial consists of three cohorts:

Cohort 1 (n=479): randomized 1:1 to receive BRUKINSA (n=241) or bendamustine plus rituximab (n=238) until disease progression or unacceptable toxicity, in patients not harboring del(17p); data from this group comprise the primary endpoint;
Cohort 2 (n=110): patients with del(17p) receiving BRUKINSA as a monotherapy; and
Cohort 3/arm D (n=114): 66 patients with del(17p) and/or pathogenic TP53 mutation received BRUKINSA in combination with venetoclax. While patients without del(17p) (n=48) were later included in this cohort, the data presented at EHA (Free EHA Whitepaper)2024 do not include these patients.
The results of Cohort 1 of the SEQUOIA study led to the regulatory approval of zanubrutinib monotherapy in the treatment of TN CLL in many countries across the world, including approvals by the U.S. Food and Drug Administration and the European Medicines Agency. Patients with del(17p) were not randomized in the Cohort 1 study, as these patients are known to experience poor clinical outcomes and poor response to chemoimmunotherapy, the control arm of the study. The primary endpoint of the trial is independent review committee-assessed PFS. Secondary endpoints include investigator-assessed PFS, IRC- and investigator-assessed ORR, overall survival, PFS and ORR in patients with del(17p), and safety. Results for Cohort 2 (arm C), representing high-risk patients treated with BRUKINSA monotherapy, were presented at the 62nd ASH (Free ASH Whitepaper) Annual Meeting in December 2020.1 This cohort of patients with del(17p) achieved significant efficacy, with an 18-month PFS of 90.6%, as assessed by investigator. Full study results were published in Lancet Oncology.2

About BRUKINSA (zanubrutinib)

BRUKINSA is a small molecule inhibitor of Bruton’s tyrosine kinase (BTK) designed to deliver complete and sustained inhibition of the BTK protein by optimizing bioavailability, half-life, and selectivity. With differentiated pharmacokinetics compared with other approved BTK inhibitors, BRUKINSA has been demonstrated to inhibit the proliferation of malignant B cells within a number of disease-relevant tissues.

U.S. Indications and Important Safety Information for BRUKINSA (zanubrutinib)

INDICATIONS

BRUKINSA is a kinase inhibitor indicated for the treatment of adult patients with:

Chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL).
Waldenström’s macroglobulinemia (WM).
Mantle cell lymphoma (MCL) who have received at least one prior therapy.
Relapsed or refractory marginal zone lymphoma (MZL) who have received at least one anti-CD20-based regimen.
Relapsed or refractory follicular lymphoma (FL), in combination with obinutuzumab, after two or more lines of systemic therapy.
The MCL, MZL and FL indications are approved under accelerated approval based on overall response rate and durability of response. Continued approval for these indications may be contingent upon verification and description of clinical benefit in confirmatory trials.

IMPORTANT SAFETY INFORMATION

Warnings and Precautions

Hemorrhage

Fatal and serious hemorrhage has occurred in patients with hematological malignancies treated with BRUKINSA. Grade 3 or higher hemorrhage including intracranial and gastrointestinal hemorrhage, hematuria, and hemothorax was reported in 3.8% of patients treated with BRUKINSA in clinical trials, with fatalities occurring in 0.2% of patients. Bleeding of any grade, excluding purpura and petechiae, occurred in 32% of patients.

Bleeding has occurred in patients with and without concomitant antiplatelet or anticoagulation therapy. Coadministration of BRUKINSA with antiplatelet or anticoagulant medications may further increase the risk of hemorrhage.

Monitor for signs and symptoms of bleeding. Discontinue BRUKINSA if intracranial hemorrhage of any grade occurs. Consider the benefit-risk of withholding BRUKINSA for 3-7 days before and after surgery depending upon the type of surgery and the risk of bleeding.

Infections

Fatal and serious infections (including bacterial, viral, or fungal infections) and opportunistic infections have occurred in patients with hematological malignancies treated with BRUKINSA. Grade 3 or higher infections occurred in 26% of patients, most commonly pneumonia (7.9%), with fatal infections occurring in 3.2% of patients. Infections due to hepatitis B virus (HBV) reactivation have occurred.

Consider prophylaxis for herpes simplex virus, pneumocystis jirovecii pneumonia, and other infections according to standard of care in patients who are at increased risk for infections. Monitor and evaluate patients for fever or other signs and symptoms of infection and treat appropriately.

Cytopenias

Grade 3 or 4 cytopenias, including neutropenia (21%), thrombocytopenia (8%) and anemia (8%) based on laboratory measurements, developed in patients treated with BRUKINSA. Grade 4 neutropenia occurred in 10% of patients, and Grade 4 thrombocytopenia occurred in 2.5% of patients.

Monitor complete blood counts regularly during treatment and interrupt treatment, reduce the dose, or discontinue treatment as warranted. Treat using growth factor or transfusions, as needed.

Second Primary Malignancies

Second primary malignancies, including non-skin carcinoma, have occurred in 14% of patients treated with BRUKINSA. The most frequent second primary malignancy was non-melanoma skin cancers (8%), followed by other solid tumors in 7% of the patients (including melanoma in 1% of patients) and hematologic malignancies (0.7%). Advise patients to use sun protection and monitor patients for the development of second primary malignancies.

Cardiac Arrhythmias

Serious cardiac arrhythmias have occurred in patients treated with BRUKINSA. Atrial fibrillation and atrial flutter were reported in 4.4% patients treated with BRUKINSA, including Grade 3 or higher cases in 1.9% of patients. Patients with cardiac risk factors, hypertension, and acute infections may be at increased risk. Grade 3 or higher ventricular arrhythmias were reported in 0.3% of patients.

Monitor for signs and symptoms of cardiac arrhythmias (e.g., palpitations, dizziness, syncope, dyspnea, chest discomfort), manage appropriately, and consider the risks and benefits of continued BRUKINSA treatment.

Hepatotoxicity, Including Drug-Induced Liver Injury

Hepatotoxicity, including severe, life-threatening, and potentially fatal cases of drug-induced liver injury (DILI), has occurred in patients treated with Bruton tyrosine kinase inhibitors, including BRUKINSA.

Evaluate bilirubin and transaminases at baseline and throughout treatment with BRUKINSA. For patients who develop abnormal liver tests after BRUKINSA, monitor more frequently for liver test abnormalities and clinical signs and symptoms of hepatic toxicity. If DILI is suspected, withhold BRUKINSA. Upon confirmation of DILI, discontinue BRUKINSA.

Embryo-Fetal Toxicity

Based on findings in animals, BRUKINSA can cause fetal harm when administered to a pregnant woman. Administration of zanubrutinib to pregnant rats during the period of organogenesis caused embryo-fetal toxicity, including malformations at exposures that were 5 times higher than those reported in patients at the recommended dose of 160 mg twice daily. Advise women to avoid becoming pregnant while taking BRUKINSA and for 1 week after the last dose. Advise men to avoid fathering a child during treatment and for 1 week after the last dose. If this drug is used during pregnancy, or if the patient becomes pregnant while taking this drug, the patient should be apprised of the potential hazard to a fetus.

Adverse Reactions

The most common adverse reactions (≥30%), including laboratory abnormalities, in patients who received BRUKINSA (N=1729) are decreased neutrophil count (51%), decreased platelet count (41%), upper respiratory tract infection (38%), hemorrhage (32%), and musculoskeletal pain (31%).

Drug Interactions

CYP3A Inhibitors: When BRUKINSA is co-administered with a strong CYP3A inhibitor, reduce BRUKINSA dose to 80 mg once daily. For coadministration with a moderate CYP3A inhibitor, reduce BRUKINSA dose to 80 mg twice daily.

CYP3A Inducers: Avoid coadministration with strong or moderate CYP3A inducers. Dose adjustment may be recommended with moderate CYP3A inducers.

Specific Populations

Hepatic Impairment: The recommended dose of BRUKINSA for patients with severe hepatic impairment is 80 mg orally twice daily.

Please see full U.S. Prescribing Information including U.S. Patient Information.

This information is intended for a global audience. Product indications vary by region.