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.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

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.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"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.

On June 14, 2024 Immune-Onc Therapeutics, Inc. ("Immune-Onc"), a clinical-stage biopharmaceutical company advancing novel therapies in immunology and oncology by targeting myeloid cell inhibitory receptors, reported the company will present additional positive interim Phase 1b expansion cohort data for IO-202 in patients with chronic myelomonocytic leukemia (CMML) at the 2024 European Hematology Association (EHA) (Free EHA Whitepaper) Annual Meeting held virtually and in Madrid, Spain, June 13 – 16 (Press release, Immune-Onc Therapeutics, JUN 14, 2024, View Source [SID1234644351]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

CMML is a rare hematologic malignancy with poor survival outcomes, incurable with conventional therapy, and has no effective standard of care. Currently, hypomethylating agents (HMA), including azacitidine (AZA), are the only FDA-approved treatment option for CMML with only a 7-17% complete remission (CR) rate.

Promising early-cycle responses, including a 53.8% (7 out of 13) CR rate (4 CR, 1 CR equivalent, and 2 CR bilineage), based on International Working Group 2023 response criteria, were observed in CMML patients treated with IO-202 in combination with AZA, with CRs lasting ten months and ongoing. The Phase 1b interim data continue to demonstrate that IO-202 is well tolerated.

"Chronic myelomonocytic leukemia remains a disease with poor prognosis and risk of progression into acute myeloid leukemia (AML), resulting in a critical need for innovative medicines," said IO-202 Phase 1b investigator Courtney DiNardo, M.D., MSCE, professor, Department of Leukemia, Division of Cancer Medicine at The University of Texas MD Anderson Cancer Center, Houston, TX. "We are encouraged by Phase 1b trial data showing early and sustained complete remissions among CMML patients, regardless of their prognosis or mutation status. This supports the potential of IO-202 in combination with azacitidine as a frontline therapy for CMML patients, and we are pleased to share these data with the medical community at EHA (Free EHA Whitepaper) this year."

"IO-202 has favorable tolerability, a well-understood mechanism of action, and a consistent efficacy response that supports further study as a treatment option in both AML and CMML patients," said Charlene Liao, Ph.D., chief executive officer of Immune-Onc. "We look forward to continued collaborations with our investigators and the FDA to plan and conduct our registrational study in frontline CMML patients."

Poster presentation details:

Abstract Number: P792 (here)
Title: Targeting LILRB4 (ILT3) Using IO-202 in Patients with Chronic Myelomonocytic Leukemia (CMML): Interim Efficacy, Safety, and Mechanism of Action Data from the Phase 1b Expansion Cohort
Presenter: Ahmed Aribi, M.D., assistant professor, Division of Leukemia, City of Hope in Duarte, CA
Session Title: Myelodysplastic Syndromes – Clinical
Session Date and Time: Friday, June 14, 6-7 p.m. CEST

ABOUT CHRONIC MYELOMONOCYTIC LEUKEMIA (CMML)

CMML is a rare form of blood cancer, occurring in 4 of every 1,000,000 people in the United States each year,1 or about 1,100 annual cases.2 CMML is characterized by a high monocyte count (>1×109/L peripheral monocytes with monocytes ≥ 10% of white blood count) and dysplastic features in the bone marrow.1 Current FDA-approved therapies for CMML are all hypomethylating agents, including azacitidine, only achieving a 7%-17% complete response rate.1

ABOUT LILRB4 (also known as ILT3)

LILRB4, also known as ILT3, is an immune-modulatory transmembrane protein found on monocytes and monocyte-derived cells. LILRB4 is expressed on certain hematologic cancer cells, such as myelomonocytic leukemia blasts, and on certain pathogenic cells involved in autoimmunity and inflammatory processes.

ABOUT IO-202

IO-202 is a first-in-class IgG1 antibody with specific, high-affinity binding to LILRB4 and depletes LILRB4 positive cells via antibody-dependent cellular cytotoxicity and antibody-dependent cellular phagocytosis. As such, IO-202 is a targeted therapy with broad potential in blood cancers and autoimmune and inflammatory diseases.

IO-202 has completed the dose escalation part of the first-in-human, multicenter, open-label Phase 1 study in the U.S., and the data was presented at the European Hematology Association (EHA) (Free EHA Whitepaper) Congress in 2023. This Phase 1 trial has advanced to the dose expansion stage to evaluate IO-202 in combination with azacitidine (NCT04372433) in patients with newly diagnosed chronic myelomonocytic leukemia (CMML) who have not received any hypomethylating agents (HMA).

The U.S. Food and Drug Administration granted IO-202 Fast Track Designations for the treatment of patients with relapsed or refractory acute myeloid leukemia (AML) and relapsed or refractory CMML, respectively. The FDA has also granted IO-202 Orphan Drug Designations for the treatment of AML and CMML, respectively.

On June 14, 2024 Molecular Partners AG (SIX: MOLN; NASDAQ: MOLN), a clinical-stage biotech company developing a new class of custom-built protein drugs known as DARPin therapeutics, reported preclinical proof-of-concept data from MP0621, a multispecific cKit x CD16a x CD47 Switch-DARPin program (Press release, Molecular Partners, JUN 14, 2024, View Source [SID1234644312]). The data validates the Switch-DARPin concept in vivo and MP0621’s potential as a next-generation therapeutic supporting hematopoietic stem cell transplantation (HSCT), initially for the treatment of acute myeloid leukemia (AML) patients. The data will be presented today in a poster session at the European Hematology Association (EHA) (Free EHA Whitepaper) 2024 Hybrid Congress taking place June 13-16 in Madrid, Spain.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"We designed our Switch-DARPin platform to unlock undruggable targets and enable safe use of powerful immune activators via logic-gated and reversible immune activation," said Anne Goubier, Ph.D., SVP Research & Early Development. "MP0621 is our first candidate in this series, with the aim to clear HSCs effectively and safely, by targeting cKit, engaging innate immune cells via CD16a, and blocking CD47 only on cKit+ cells. We’re thrilled by these results, which validate our Switch-DARPin platform in vitro and in vivo and pave the way for a new generation of conditionally activated T cell engagers, with the potential to revolutionize therapy in areas of unmet need, such as solid tumors".

HSCT offers a potential cure for patients with AML and other malignant and non-malignant diseases. However, the toxicity of pre-HSCT conditioning often requires that it is carried out with reduced intensity, increasing the likelihood that diseased cells remain in the bone marrow and lead to relapse. Safer and more efficacious treatments are needed to improve HSCT outcomes for more patients with AML and other diseases requiring HSC transplant. MP0621 is intended to maximize the therapeutic potential of HSCT for AML patients, including those with poor cytogenetic risk profile, to extend the access to potentially curative HSCT for more patients, and to increase long term disease control post HSCT.

MP0621 is designed to induce eradication of HSCs while avoiding the toxicity associated with current high-intensity conditioning regimens. MP0621 engages natural killer cells and macrophages via CD16a to selectively kill targeted cKit-positive cells. cKit is critical for stem cell maintenance and renewal and thus an attractive target to select for HSCs as well as leukemic stem cells in AML. CD47 is widely expressed as "don’t-eat-me" signal and prevents killing of cells, including HSCs/LSCs. Blocking CD47 can enhance damage to bound stem cells; however systemic anti-CD47 blockers cause significant toxicity, highlighting the need for conditional and targeted blockade of CD47.

The Switch-DARPin platform provides a logic-gated "on/off" function (the "Switch") to multispecific DARPin candidates leading to target activation only in the presence of defined antigens. In MP0621, the Switch-DARPin binds to either cellular cKit or to the anti-CD47 DARPin binder. Upon MP0621 binding to cKit on cells, the Switch-DARPin will unmask the anti-CD47 DARPin, which in turn will bind CD47 and block the "don’t-eat-me" signal, leveraging the power of CD47 inhibition without its associated toxicity to healthy cells. The Company is presently conducting preclinical efficacy and safety studies for MP0621 with data expected in H2 2024.

In the poster presented, preclinical studies demonstrate that:

MP0621 selectively blocks CD47 on cells expressing cKit
Conditional blockade of CD47 enhances efficacy of cKit targeting, with phagocytosis comparable to a combo of anti-cKit and anti-CD47 monoclonal antibodies
MP0621 depleted cKit+ cells in bone marrow of humanized mice without affecting circulating immune cells
PK profile of MP0621 is suitable for HSCT therapy in humans
Poster details can be found below. The full poster will be made available on Molecular Partners’ website after the presentation.

Title: C-KIT X CD16A X CD47 Switch-DARPin with Conditional Blockade of CD47: A Next-generation Targeted Conditioning for Hematopoietic Stem Cell Transplantation
Session Title: Stem Cell Transplantation – Experimental
Abstract Number for Publication: P1294
Poster Session Timing: June 14, 2024; 6-7 pm CET

On June 14, 2024 Bio-Path Holdings, Inc., (NASDAQ:BPTH), a biotechnology company leveraging its proprietary DNAbilize liposomal delivery and antisense technology to develop a portfolio of targeted nucleic acid cancer drugs, reported interim results from the Company’s Phase 2 study of prexigebersen (BP1001) in combination with decitabine and venetoclax for the treatment of acute myeloid leukemia (AML) in a poster presentation at 2024 European Hematology Association (EHA) (Free EHA Whitepaper) Congress, on June 14, 2024 in Madrid, Spain (Press release, Bio-Path Holdings, JUN 14, 2024, View Source [SID1234644332]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

Jorge Cortes, M.D., Director of the Georgia Cancer Center, presented data showing prexigebersen continues to be well-tolerated and has now demonstrated compelling efficacy results in two reporting cohorts including evaluable newly diagnosed AML patients and evaluable refractory/relapsed AML patients, both of which exceeded outcomes with frontline therapy. "It was a pleasure to present these compelling data to an audience of European oncologists who treat AML patients and understand the continued great need for new therapeutic options," said Peter Nielsen, Chief Executive Officer of Bio-Path.

"Given that our study is being conducted in the U.S., this encore presentation is an important step towards educating global oncology leaders on the benefits of prexigebersen and its potential to be another tool in their fight against AML."

Data Highlights

In Cohort 1, 31 newly diagnosed patients were enrolled; 20 evaluable patients (9 male: 45%) with a median age of 75 years (range, 69-84), treated with at least one cycle of prexigebersen, decitabine and venetoclax, had adverse-risk (n=12, 2017 ELN guidelines) or secondary AML (sAML; n=7) evolved from myelodysplastic syndromes (n=4), chronic myelomonocytic leukemia (n=1) or treatment-related AML (n=2). Fifteen patients (75% of evaluable; 54% of enrolled) achieved complete remission (CR), CRh (CR with partial recovery of peripheral blood counts), or CRi (CR with incomplete hematologic recovery); two patients achieved partial remission (PR) and two patients achieved stable disease (SD).

In Cohort 2, 38 relapsed/refractory patients were enrolled; 23 evaluable patients (13 male: 57%) with a median age of 63 years (range, 24-89), treated with at least one cycle of prexigebersen, decitabine and venetoclax, had adverse-risk (n=13) or sAML (n=5). Twelve patients (55% of evaluable; 32% of enrolled) achieved CR/CRi/CRh; one patient achieved PR, eight patients achieved SD and one patient had treatment failure.

Among the evaluable patients of both cohorts, adverse events were consistent with those expected with decitabine and venetoclax and/or AML, including fatigue (72%), anemia (60%) and neutropenia (49%), while the most frequent severe adverse events were febrile neutropenia (26%) and sepsis (5%). Given these promising interim results, Bio-Path expects to continue enrollment of up to 98 and 54 evaluable patients for Cohorts 1 and 2, respectively.