On December 10, 2022 ImmunoGen, Inc. (Nasdaq: IMGN), a leader in the expanding field of antibody-drug conjugates (ADCs) for the treatment of cancer, reported initial safety and efficacy findings from dose-escalation and expansion cohorts of the Phase 1b/2 study of pivekimab sunirine (pivekimab) in combination with Vidaza (azacitidine) and Venclexta (venetoclax) in patients with relapsed/refractory (R/R) and frontline acute myeloid leukemia (AML) (Press release, ImmunoGen, DEC 10, 2022, View Source [SID1234625021]). These findings were presented in an oral session at the 64th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting in New Orleans, Louisiana.

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!

"While azacitidine and venetoclax have improved outcomes for patients with frontline AML, overall survival unfortunately remains poor in both this population and those with relapsed/refractory AML," said Naval Daver, MD, Associate Professor in the Department of Leukemia at The University of Texas MD Anderson Cancer Center. "I am very encouraged by the broad anti-leukemia activity of this triplet, particularly the compelling CR/CRh rates in subgroups of relapsed/refractory AML including first relapse and those with IDH2 or FLT3 mutations as well the preliminary data showing encouraging tolerability and complete responses in the frontline setting."

BROAD ACTIVITY FOR THE PIVEKIMAB SUNIRINE, AZACITIDINE, AND VENETOCLAX TRIPLET IN HIGH-RISK PATIENTS WITH RELAPSED/REFRACTORY ACUTE MYELOID LEUKEMIA (Abstract #62)
Lead Author: Naval Daver, MD
Oral Session: 616
Session Date: December 10, 2022
Session Time: 10:30 AM – 12:00 PM ET

Key findings from the open-label, multicenter, Phase 1b/2 study of pivekimab in combination with azacitidine and venetoclax in patients with R/R and frontline CD123-positive AML include:

Safety:

91 patients with CD123-positive R/R AML received pivekimab at 15 mcg/kg or 45 mcg/kg on day 7, azacitidine at 50 mg/m2 or 75 mg/m2 on days 1-7, and venetoclax at 400 mg daily for 8, 14 or 21 days per 28-day cycle.
The triplet displayed a manageable safety profile in R/R AML patients.
The most common treatment emergent adverse events (all grades [grade 3+ events]) were febrile neutropenia (33%, [29%]), thrombocytopenia (23%, [20%]), dyspnea (22% [6%]), infusion-related reactions (22%, [2%]), hypokalemia (21% [2%]) and fatigue (20% [2%]).
Rates of cytopenias were similar to those observed with a hypomethylating agent and venetoclax.
No tumor lysis syndrome, veno-occlusive disease, capillary leak syndrome, or cytokine release syndrome were reported.
Discontinuations due to pivekimab-related adverse events were 5%.
30-day mortality was 6%, with no treatment-related deaths.
Anti-leukemia activity:

In the R/R cohort, objective response rate (ORR [CR, CRh, CRp, CRi, MLFS) was 45% with a composite complete remission (CCR [CR, CRh, CRp, CRi]) rate of 25%.
Venetoclax-naïve patients had an ORR of 53% and CCR of 38%; in patients who had prior venetoclax exposure, the ORR was 36% and CCR was 11%.
Responses were observed in 9 of 11 patients with FLT3-ITD AML with an ORR of 82% and a CCR of 64%.
Enrollment in the R/R cohort is complete.
In the 10 frontline patients enrolled, pivekimab was administered at 45 mcg/kg on day 7, azacitidine at 75 mg/m2 on days 1-7, and venetoclax at 400 mg for at least 14 days per 28-day cycle.
5/10 (50%) patients achieved a CR and 3/4 (75%) patients tested had a minimal residual disease (MRD)-negative CR.
At the time of data cut-off, 5 patients remain on treatment.
Enrollment in the frontline cohort continues in the US and EU.
"These data presented at ASH (Free ASH Whitepaper) demonstrate this triplet’s encouraging anti-leukemia activity and tolerability, and reinforce our belief in pivekimab’s potential as a novel addition to the azacitidine and venetoclax regimen for AML," said Anna Berkenblit, MD, Senior Vice President and Chief Medical Officer of ImmunoGen. "Based upon the strong results from the first 10 frontline patients we have enrolled, we have moved forward with gathering more data for the triplet using 14 days of venetoclax and have opened a second cohort of up to 50 frontline patients with a goal of evaluating up to 28 days of venetoclax per cycle to optimize the duration of therapy. Tolerability and efficacy outcomes from these cohorts will guide pivotal development of the triplet in frontline AML."

Additional information can be found at View Source, including abstracts.

ABOUT PIVEKIMAB SUNIRINE
Pivekimab sunirine is a CD123-targeting ADC in clinical development for hematological malignancies, including blastic plasmacytoid dendritic cell neoplasm (BPDCN), acute myeloid leukemia (AML), and other CD123+ hematologic malignancies. Pivekimab is being evaluated as monotherapy for patients with BPDCN, as a doublet with magrolimab in patients with relapsed/refractory AML, and as a triplet with Vidaza (azacitidine) and Venclexta (venetoclax) in patients with frontline AML. Pivekimab uses one of ImmunoGen’s novel indolinobenzodiazepine (IGN) payloads, which alkylate DNA and cause single strand breaks without crosslinking. IGNs are designed to have high potency against tumor cells and have been observed in preclinical studies and clinical trials to have less toxicity to normal marrow progenitors than other DNA-targeting payloads. The European Medicines Agency (EMA) granted orphan drug designation to pivekimab for the treatment of BPDCN in June 2020. Pivekimab also holds this designation in the US. In October 2020, the FDA granted pivekimab Breakthrough Therapy designation in relapsed/refractory BPDCN.

ABOUT ACUTE MYELOID LEUKEMIA (AML)
AML is a cancer of the bone marrow cells that produce white blood cells. It causes the marrow to increasingly generate abnormal, immature white blood cells (blasts) that do not mature into effective infection-fighting cells. The blasts quickly fill the bone marrow, impacting the production of normal platelets and red blood cells. The resulting deficiencies in normal blood cells leave the patient vulnerable to infections, bleeding problems, and anemia. It is estimated that, in the US alone, more than 20,000 people will be diagnosed with AML and more than 11,000 will die from the disease this year.

ABOUT CD123
CD123, the interleukin-3 alpha chain, is expressed on multiple myeloid and lymphoid cancers including AML, BPDCN, ALL, chronic myeloid leukemia, and myeloproliferative neoplasms. With limited expression on normal hematopoietic cells, rapid internalization, and expression on AML leukemia stem cells, CD123 is a clinically validated therapeutic target.

On December 10, 2022 Fate Therapeutics, Inc. (NASDAQ: FATE), a clinical-stage biopharmaceutical company dedicated to the development of programmed cellular immunotherapies for patients with cancer, reported interim clinical data from the dose-escalation stage of its ongoing Phase 1 study of FT819 for patients with relapsed / refractory B-cell lymphoma (r/r BCL) at the 64th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting and Exposition (Press release, Fate Therapeutics, DEC 10, 2022, View Source [SID1234625019]). The landmark trial is the first-ever clinical investigation of a T-cell product candidate manufactured from a clonal master induced pluripotent stem cell (iPSC) line, a renewable cell source that enables mass production of engineered T-cell therapies with greater product consistency, off-the-shelf availability, and broader patient accessibility. FT819 incorporates several first-of-kind features including the integration of a novel CD19-targeted 1XX chimeric antigen receptor (CAR) construct into the T-cell receptor alpha constant (TRAC) locus, which is intended to promote uniform CAR expression, enhance T-cell potency, and prevent graft-versus-host disease (Eyquem et al. Nature, 543, 113–117, 2017).

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 are very excited about the early safety and efficacy data emerging from our groundbreaking clinical study of the first-ever iPSC-derived T-cell therapy. Data from the initial dose-escalation cohorts of a single dose of FT819 are indicative of a favorable safety profile and clearly demonstrate activity in heavily pre-treated patients with aggressive large B-cell lymphoma, including in patients that were not eligible for or had previously failed autologous CD19-targeted CAR T-cell therapy," said Scott Wolchko, President and Chief Executive Officer of Fate Therapeutics. "In addition to the rapid responses we observed with a single dose of FT819, the ability to quickly intervene upon the first signs of disease recurrence is a differentiating benefit of off-the-shelf cell therapy and we are also excited by the reinduction of objective response with the administration of a second cycle of FT819 to a patient following disease progression."

Interim Phase 1 Dose-escalation Efficacy Data
The multi-center Phase 1 clinical trial of FT819 is designed to assess its safety and clinical activity in adult patients with r/r BCL and to determine the recommended Phase 2 dose and schedule. As of the September 8, 2022 data cutoff date, 10 patients with aggressive large B-cell lymphoma have been treated with FT819, including 8 patients in Regimen A with a single dose of FT819 and 2 patients in Regimen B with three fractionated doses of FT819 on Days 1, 3, and 5. Patients received standard conditioning chemotherapy consisting of cyclophosphamide (Cy) at 500 mg/m2 and fludarabine (Flu) at 30 mg/m2 for 3 days prior to the initiation of each regimen. Patients were heavily pre-treated having received a median of 4 prior lines of therapy (range 3-7), including 7 of 10 patients (70%) having previously received autologous CD19-targeted CAR T-cell therapy.

In Regimen A, of the 8 patients with aggressive large B-cell lymphoma (median of 4.5 prior lines of therapy [range 3-7]) treated with a single dose of FT819 ranging from 90 million cells to 360 million cells (see Table 1):

1 of 2 patients naïve to CAR T-cell therapy achieved an objective response (1 CR) at Day 30, which was a complete response in a patient with diffuse large B-cell lymphoma (DLBCL) previously treated with 5 prior lines of therapy; and
2 of 6 patients previously treated with CAR T-cell therapy achieved an objective response (1 CR, 1 PR) at Day 30, which included a complete response in a patient with DLBCL previously treated with 7 prior lines of therapy who did not respond to autologous CD19-targeted CAR T-cell therapy.
In Regimen B, 2 patients with aggressive large B-cell lymphoma (each of whom received 3 prior lines of therapy) treated with three fractionated doses at 30 million cells per dose did not respond to therapy at Day 30.

Table 1: Aggressive Large B-cell Lymphoma 1,2,3
FT819 Regimen A: Single Dose (n=8)
CAR T-cell Therapy Naïve Prior CAR T-cell Therapy
Cells 90M 180M 360M 90M 180M 360M
N 1 n/a 1 4 1 1
OR / CR 0 / 0 n/a 1 / 1 2 / 1 0 / 0 0 / 0
FT819 Regimen B: Three Fractionated Doses (n=2)
CAR T-cell Therapy Naïve Prior CAR T-cell Therapy
Cells / Dose 30M 30M
N 1 1
OR / CR 0 / 0 0 / 0
OR = objective response; CR = complete response; M = million
1 As of data cutoff date of September 8, 2022
2 Includes diffuse large B-cell lymphoma (n=8) and high-grade B-cell lymphoma (n=2)
3 Day 30 protocol-defined response assessment per Lugano 2014 criteria
As of the September 8, 2022 data cutoff date, an additional 5 patients with r/r BCL have been treated with FT819. One patient with Grade 3a follicular lymphoma (with 5 prior lines of therapy, including CAR T-cell therapy) treated in Regimen A with a single dose of FT819 at 180 million cells achieved a complete response at Day 30. Four patients with Richter’s Transformation (median of 5.5 prior lines of therapy [range 2-9]) did not respond to therapy at Day 30.

Interim Phase 1 Dose-escalation Safety Data
No dose-limiting toxicities, and no Grade 3 or greater FT819-related adverse events (AEs) or serious AEs, were observed. Of the 15 patients treated in Regimens A and B, three patients (20%) experienced Grade 2 cytokine release syndrome (CRS) characterized by fever, hypotension, and hypoxia, which events resolved with single-dose tocilizumab and supportive care. No treatment-emergent AEs (TEAEs) of any grade of immune effector cell-associated neurotoxicity syndrome (ICANS) or graft-versus-host disease (GvHD) were reported by investigators. The FT819 treatment regimen was well tolerated. Grade 3 or greater TEAEs not related to FT819 primarily included hematologic cytopenias associated with conditioning chemotherapy. There were no study discontinuations or deaths due to TEAEs other than one patient with stable disease who died on Day 38 due to sepsis not considered related to FT819 by the study investigator.

FT819 Patient Case Study: Retreatment to Reinduce Response
The ASH (Free ASH Whitepaper) presentation featured a patient case study demonstrating the potential to safely administer more than one treatment cycle of FT819 and reinduce an objective response following disease progression. The 73 year-old female with DLBCL had previously been treated with 4 prior lines of therapy, including commercial autologous CD19-targeted CAR T-cell therapy with best response of PR, and was refractory to last prior therapy (investigational cord blood-derived NK cell therapy). The patient received a first treatment cycle with a single dose of FT819 at 90 million cells, achieving a PR at Day 30 with 94% reduction in size of target lesions. Continued follow-up through November 8, 2022 was significant for disease progression on Day 72, for which the patient received a second treatment cycle with a single dose of FT819 at 180 million cells on Day 134 with consent from the U.S. Food and Drug Administration and achieved a PR at Day 163 with 61% reduction in size of target lesions. Both treatment cycles were well tolerated with no Grade 3 or greater FT819-related AEs or serious AEs, no reports of any grade of CRS, ICANS, or GvHD, and no evidence of new or worsening toxicity with the second treatment cycle. Following each treatment cycle, FT819 was detected in the peripheral blood with peak level at Day 4 in Cycle 1 and at Day 8 in Cycle 2, with maximum peak level at Day 8 in Cycle 2 at 8,152 transgene copies/μg DNA.

Dose escalation is currently ongoing in Regimen A as a single dose of FT819 at 360 million cells and in Regimen B with three fractionated doses at 60 million cells per dose. The Company has also amended the FT819 study protocol to allow for the use of bendamustine at 90 mg/m2 for 2 days as an alternative to Cy / Flu conditioning chemotherapy.

About Fate Therapeutics’ iPSC Product Platform
The Company’s proprietary induced pluripotent stem cell (iPSC) product platform enables mass production of off-the-shelf, engineered, homogeneous cell products that are designed to be administered with multiple doses to deliver more effective pharmacologic activity, including in combination with other cancer treatments. Human iPSCs possess the unique dual properties of unlimited self-renewal and differentiation potential into all cell types of the body. The Company’s first-of-kind approach involves engineering human iPSCs in a one-time genetic modification event and selecting a single engineered iPSC for maintenance as a clonal master iPSC line. Analogous to master cell lines used to manufacture biopharmaceutical drug products such as monoclonal antibodies, clonal master iPSC lines are a renewable source for manufacturing cell therapy products which are well-defined and uniform in composition, can be mass produced at significant scale in a cost-effective manner, and can be delivered off-the-shelf for patient treatment. As a result, the Company’s platform is uniquely designed to overcome numerous limitations associated with the production of cell therapies using patient- or donor-sourced cells, which is logistically complex and expensive and is subject to batch-to-batch and cell-to-cell variability that can affect clinical safety and efficacy. Fate Therapeutics’ iPSC product platform is supported by an intellectual property portfolio of over 350 issued patents and 150 pending patent applications.

About FT819
FT819 is an investigational, universal, off-the-shelf, T-cell receptor (TCR)-less CD19 chimeric antigen receptor (CAR) T-cell cancer immunotherapy derived from a clonal master induced pluripotent stem cell (iPSC) line, which is engineered with the following features designed to improve the safety and efficacy of CAR19 T-cell therapy: a novel 1XX CAR signaling domain, which has been shown to extend T-cell effector function without eliciting exhaustion; integration of the CAR19 transgene directly into the T-cell receptor alpha constant (TRAC) locus, which has been shown to promote uniform CAR19 expression and enhanced T-cell potency; and complete bi-allelic disruption of TCR expression for the prevention of graft-versus-host disease. FT819 demonstrated antigen-specific cytolytic activity in vitro against CD19-expressing leukemia and lymphoma cell lines comparable to that of primary CAR T cells, and persisted and maintained tumor clearance in the bone marrow in an in vivo disseminated xenograft model of lymphoblastic leukemia. FT819 is being investigated in a multicenter Phase 1 clinical trial for the treatment of relapsed / refractory B-cell malignancies, including B-cell lymphoma, chronic lymphocytic leukemia, and acute lymphoblastic leukemia (NCT04629729).

On December 10, 2022 Fate Therapeutics, Inc. (NASDAQ: FATE), a clinical-stage biopharmaceutical company dedicated to the development of programmed cellular immunotherapies for patients with cancer, reported interim clinical data from the dose-escalation stage of its ongoing Phase 1 study of FT576 for patients with relapsed / refractory multiple myeloma (r/r MM) at the 64th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting and Exposition (Press release, Fate Therapeutics, DEC 10, 2022, View Source [SID1234625018]). The off-the-shelf product candidate, which is derived from a clonal master engineered induced pluripotent stem cell (iPSC) line, incorporates a chimeric antigen receptor (CAR) targeting B-cell maturation antigen (BCMA) as well as a high-affinity, non-cleavable CD16 (hnCD16) Fc receptor to maximize antibody-dependent cellular cytotoxicity (ADCC) and enable dual-antigen targeting of myeloma cells through combination with monoclonal antibody (mAb) therapy. Preclinical data published last month in the journal Nature Communications (Cichocki et al. 2022, 13:7341) demonstrated that single-dose administration of FT576 was effective at controlling tumor growth in vivo, with deeper and more sustained anti-tumor activity observed through multi-dose administration of FT576 as well as in combination with the CD38-targeted monoclonal antibody daratumumab.

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 interim Phase 1 data from the low-dose cohorts of single-dose administration of FT576 in patients with relapsed / refractory disease provide encouraging clinical evidence of BCMA-targeted activity," said Yu-Waye Chu, Chief Medical Officer of Fate Therapeutics. "In addition, initial safety observations of FT576 as monotherapy and in combination with daratumumab, with no reported events of cytokine release syndrome and ICANS as well as no study discontinuations due to treatment-emergent adverse events, indicate that the off-the-shelf product candidate has the potential to be safely administered in the outpatient setting. Dose escalation is currently ongoing with multi-dose regimens, and we look forward to evaluating the effect of increasing dose and dose frequency to define the product candidate’s therapeutic profile."

Interim Phase 1 Dose-escalation Efficacy Data
The multi-center Phase 1 clinical trial of FT576 is designed to assess its safety and clinical activity in adult patients with r/r MM, and to determine the recommended Phase 2 dose and schedule, as monotherapy (Regimen A) and in combination with daratumumab to simultaneously target BCMA and CD38 (Regimen B). As of the October 7, 2022 data cutoff date, 9 patients with r/r MM have been treated with a single dose of FT576, including 6 patients in Regimen A and 3 patients in Regimen B (see Table 1). Patients received standard conditioning chemotherapy consisting of cyclophosphamide (Cy) at 300 mg/m2 and fludarabine (Flu) at 30 mg/m2 for 3 days prior to the initiation of each regimen. Patients were heavily pre-treated having received a median of 5 prior lines of therapy (range 3-10), including 6 patients (67%) that were refractory to last therapy.

In Regimen A, 6 patients were treated with a single dose of FT576 as monotherapy in the first dose cohort at 100 million cells (n=3) and the second dose cohort at 300 million cells (n=3). In the second dose cohort, one patient, who had received 5 prior lines of therapy, was triple-refractory to an immunomodulatory drug, a proteasome inhibitor, and an anti-CD38 mAb, and was refractory to last therapy (pomalidomide, daratumumab and dexamethasone), achieved a very good partial response (VGPR) with the other two patients showing stable disease (SD). Further evidence of FT576 activity was observed in the second dose cohort, with two patients for whom serum BCMA levels were evaluable showing a substantial treatment-induced decrease in soluble BCMA.
In Regimen B, 3 patients were treated with a single dose of FT576 in combination with daratumumab in the first dose cohort at 100 million cells, with one patient achieving a partial response (PR) and one patient achieving a minor response (MR). All 3 patients showed a substantial treatment-induced decrease in soluble BCMA.
The Company has now initiated enrollment of two-dose escalation cohorts at 300 million cells per dose in both regimens.

Table 1: Patient Characteristics, Safety, and Activity 1,2
Patient Characteristics Safety Activity
Patient # # Prior Therapies Triple Refractory DLTs CRS ICANS Related ≥G3 AEs Related ≥G3 SAEs % Change in sBCMA 3 BOR
Regimen A: Single-dose FT576 as Monotherapy (n=6)
100M Single-dose FT576
1 10 N N N N Y N 2.3% PD
2 6 Y N N N Y N 50.9% PD
3 8 Y N N N N N -0.8% SD
300M Single-dose FT576
4 5 N N N N N N -30.6% SD
5 5 Y N N N N N -82.3% VGPR
6 5 N N N N N N NA SD
Regimen B: Single-dose FT576 in Combination with Daratumumab (n=3)
100M Single-dose FT576
7 3 N N N N N N -64.4% MR
8 4 N N N N N N -37.8% PR
9 5 Y N N N N N -40.3% SD
AE = adverse event; BOR = Best overall response; CRS = cytokine release syndrome; DLT = dose-limiting toxicity; ICANS = immune effector cell-associated neurotoxicity syndrome; MR = minor response; N = no; NA = not available; PD = progressive disease; PR = partial response; SAE = serious adverse event; SD = stable disease; sBCMA = soluble BCMA; VGPR = very good partial response; Y = yes
1 As of data cutoff date of October 7, 2022
2 Protocol-defined response assessment per International Myeloma Working Group (IMWG) response criteria (Kumar et al. 2016)
3 % change at Day 29 from pre-treatment baseline
Interim Phase 1 Dose-escalation Safety Data
No dose-limiting toxicities, and no events of any grade of cytokine release syndrome (CRS), immune effector cell-associated neurotoxicity syndrome (ICANS), or graft-versus-host disease (GvHD), were observed. Both FT576 treatment regimens were well tolerated. Two patients experienced Grade 3 or greater FT576-related adverse events (AEs), with one patient having Grade 3 diarrhea and one patient having two episodes of Grades 3 through 4 neutropenia and 3 episodes of Grade 3 anemia, all of which resolved. There were no serious AEs related to FT576. Grade 3 or greater treatment-emergent AEs (TEAEs) not related to FT576 primarily included hematologic cytopenias associated with conditioning chemotherapy. There were no study discontinuations or deaths due to TEAEs.

FT555 GPRC5D-targeted CAR NK Cell Program
Under its collaboration with Janssen Biotech, Inc. (Janssen), one of the Janssen Pharmaceutical Companies of Johnson & Johnson, the Company is currently conducting preclinical development of FT555, a multiplexed-engineered CAR NK cell product candidate derived from a clonal master engineered iPSC line incorporating four functional components: a proprietary CAR optimized for NK cell biology that targets GPRC5D, an orphan G-protein-coupled receptor expressed on myeloma cells with a distribution that is similar to but independent of BCMA; a novel hnCD16 Fc receptor for enhanced ADCC; an IL-15 receptor fusion (IL-15RF) that augments NK cell activity; and the deletion of the CD38 gene (CD38KO), which promotes persistence and function in high oxidative stress environments.

At ASH (Free ASH Whitepaper), scientists from the companies jointly presented preclinical data demonstrating that single-dose administration of FT555 as monotherapy resulted in robust and durable antigen-mediated tumor regression in two independent disseminated tumor models of aggressive myeloma, which activity was further improved in combination with daratumumab to simultaneously target GPRC5D and CD38 antigens. Administration of three doses of FT555 as monotherapy further improved tumor clearance and showed superior activity compared to single-dose primary CAR T cells.

In May 2022, Janssen exercised its commercial option to FT555, pursuant to which the Company granted Janssen an exclusive license for development and commercialization of FT555. The Company is eligible to receive clinical, regulatory, and commercial milestones, plus double-digit royalties on worldwide commercial sales of the product candidate. In addition, the Company retains the right to elect to co-commercialize, and share equally in profits and losses, in the United States, subject to its payment of certain clinical development costs and adjustments in milestone and royalty payments.

About Fate Therapeutics’ iPSC Product Platform
The Company’s proprietary induced pluripotent stem cell (iPSC) product platform enables mass production of off-the-shelf, engineered, homogeneous cell products that are designed to be administered with multiple doses to deliver more effective pharmacologic activity, including in combination with other cancer treatments. Human iPSCs possess the unique dual properties of unlimited self-renewal and differentiation potential into all cell types of the body. The Company’s first-of-kind approach involves engineering human iPSCs in a one-time genetic modification event and selecting a single engineered iPSC for maintenance as a clonal master iPSC line. Analogous to master cell lines used to manufacture biopharmaceutical drug products such as monoclonal antibodies, clonal master iPSC lines are a renewable source for manufacturing cell therapy products which are well-defined and uniform in composition, can be mass produced at significant scale in a cost-effective manner, and can be delivered off-the-shelf for patient treatment. As a result, the Company’s platform is uniquely designed to overcome numerous limitations associated with the production of cell therapies using patient- or donor-sourced cells, which is logistically complex and expensive and is subject to batch-to-batch and cell-to-cell variability that can affect clinical safety and efficacy. Fate Therapeutics’ iPSC product platform is supported by an intellectual property portfolio of over 350 issued patents and 150 pending patent applications.

About FT576
FT576 is an investigational, universal, off-the-shelf natural killer (NK) cell cancer immunotherapy derived from a clonal master induced pluripotent stem cell (iPSC) line engineered with four functional components: a proprietary chimeric antigen receptor (CAR) optimized for NK cell biology that targets B-cell maturation antigen (BCMA); a novel high-affinity 158V, non-cleavable CD16 (hnCD16) Fc receptor, which has been modified to prevent its down-regulation and to enhance its binding to tumor-targeting antibodies; an IL-15 receptor fusion (IL-15RF) that augments NK cell activity; and the deletion of the CD38 gene (CD38KO), which promotes persistence and function in high oxidative stress environments. In preclinical studies, FT576 has demonstrated that the high-avidity binding of the BCMA-targeted CAR construct enables sustained tumor control against various multiple myeloma cell lines, including in long-term in vivo xenograft mouse models. Additionally, in combination with daratumumab, FT576 has shown complete tumor clearance and improved survival compared to primary BCMA-targeted CAR T cells in a disseminated xenograft model of multiple myeloma. FT576 is being investigated in a multicenter Phase 1 clinical trial for the treatment of relapsed / refractory multiple myeloma as a monotherapy and in combination with daratumumab (NCT05182073).

On December 10, 2022 CRISPR Therapeutics (Nasdaq: CRSP) and Vertex Pharmaceuticals Incorporated (Nasdaq: VRTX) reported an oral, encore presentation of clinical data from patients with sickle cell disease (SCD) or transfusion-dependent beta-thalassemia (TDT) treated with the investigational therapy exagamglogene autotemcel (exa-cel) in CLIMB-111 or CLIMB-121 and followed in CLIMB-131, a long-term follow-up study (Press release, CRISPR Therapeutics, DEC 10, 2022, View Source [SID1234625015]). Vertex will also present new health economics and outcomes research from multiple studies in patients with SCD and TDT.

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 are excited to be at ASH (Free ASH Whitepaper) and share data from the pivotal exa-cel trials and from multiple real-world studies examining the burden of severe SCD and TDT," said Carmen Bozic, M.D., Executive Vice President, Global Medicines Development and Medical Affairs, and Chief Medical Officer at Vertex. "We remain on track to complete submission of the first ever CRISPR-based therapy in the EU and U.K. this year, and we have initiated our rolling submission in the U.S., which we plan to complete in Q1 2023. We are working with urgency to bring forward this potential therapy to patients who are waiting."

Vertex will have the following presentations at ASH (Free ASH Whitepaper) this year.

Oral presentation, abstract #12 combined with abstract #2137, in partnership with CRISPR Therapeutics, entitled "Efficacy and Safety of a Single Dose of Exagamglogene Autotemcel for Transfusion-Dependent Beta-Thalassemia and Severe Sickle Cell Disease," will be presented on Saturday, December 10 at 10:45 a.m CST. The presentation will include encore data as presented at the European Hematology Association (EHA) (Free EHA Whitepaper) Congress in June 2022 on patients with SCD or TDT who received the investigational therapy exa-cel in the CLIMB-111 or CLIMB-121 study and were followed in CLIMB-131, a long-term follow-up study.
Oral presentation, abstract #577, entitled "Health-Related Quality of Life, Disease Impacts, and Health Equity Concerns in Adults with Sickle Cell Disease with Recurrent Vaso-Occlusive Crises: Preliminary Results from a Global Longitudinal Survey," will be presented on Sunday, December 11 at 12:00 p.m. CST. The study quantifies the symptoms, quality of life and work impacts of living with SCD with recurrent vaso-occlusive crises (VOCs). This presentation represents preliminary results from an ongoing longitudinal study.
Poster presentation, abstract #4820, entitled "Clinical and Economic Outcomes in Patients with Transfusion-Dependent Beta-Thalassemia and Patients with Sickle Cell Disease with Recurrent Vaso-Occlusive Crises Receiving Hematopoietic Stem Cell Transplants in the United States," will be presented on Monday, December 12 from 6:00-8:00 p.m. CST. The study analyzes the demographics, transplant-related complications and costs of patients with SCD and TDT who undergo a hematopoietic stem cell transplant (HSCT) in the United States utilizing a claims database.
Poster presentation, abstract #4882, entitled "Health-Related Quality of Life and Disease Impacts in Adults with Transfusion-Dependent Beta-Thalassemia: Preliminary Results from the Global Longitudinal Survey," will be presented on Monday, December 12 from 6:00-8:00 p.m. CST. The study quantifies the symptoms, quality of life and work impacts of living with TDT. This presentation represents preliminary results from an ongoing longitudinal study.
The accepted abstracts are available online on the ASH (Free ASH Whitepaper) website.

About exagamglogene autotemcel (exa-cel)

Exa-cel, formerly known as CTX001, is an investigational, autologous, ex vivo CRISPR/Cas9 gene-edited therapy that is being evaluated for patients with SCD or TDT, in which a patient’s own hematopoietic stem cells are edited to produce 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. The elevation of HbF by exa-cel has the potential to reduce or eliminate painful and debilitating VOCs for patients with SCD and alleviate transfusion requirements for patients with TDT. Earlier results from these ongoing trials were published in The New England Journal of Medicine in January of 2021 and presented at the European Hematology Association (EHA) (Free EHA Whitepaper) Congress in June 2022.

Based on progress in this program to date, exa-cel has been granted Regenerative Medicine Advanced Therapy (RMAT), Fast Track, Orphan Drug, and Rare Pediatric Disease designations from the U.S. Food and Drug Administration (FDA) for both SCD and TDT. Exa-cel has also been granted Orphan Drug Designation from the European Commission, as well as Priority Medicines (PRIME) designation from the European Medicines Agency (EMA), for both SCD and TDT.

The companies have begun the rolling Biologics License Application (BLA) submission for exa-cel to the U.S. FDA and plan to complete the BLA by the end of the first quarter 2023 and remain on track to submit exa-cel to the Medicines and Healthcare products Regulatory Agency in the U.K. and the EMA in the European Union by the end of the year.

About CLIMB‑111 and CLIMB‑121

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 exa-cel 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 exa-cel infusion. Each patient will be asked to participate in CLIMB‑131, a long-term follow-up trial.

About CLIMB-131

The ongoing long-term, open-label trial, CLIMB-131, is designed to evaluate the safety and efficacy of exa-cel in patients who received exa-cel in CLIMB‑111, CLIMB‑121, CLIMB‑141, CLIMB‑151 or CLIMB-161. The trial is designed to follow participants for up to 15 years after exa-cel infusion.

About CLIMB‑141 and CLIMB‑151

The ongoing Phase 3 open-label trials, CLIMB‑141 and CLIMB‑151, are designed to assess the safety and efficacy of a single dose of exa-cel in patients ages 2 to 11 years with TDT or with SCD, characterized by recurrent VOCs, respectively. The trials are now open for enrollment and currently enrolling patients ages 5 to 11 years and will plan to extend to ages 2 to less than 5 years at a later date. Each trial will enroll approximately 12 patients. Patients will be followed for approximately two years after infusion. Each patient will be asked to participate in CLIMB-131, a long-term follow-up trial.

About CLIMB-161

The ongoing Phase 3b study, CLIMB-161, is to support expansion of our manufacturing footprint after initial potential approval and launch. This study will enroll approximately 12 patients with either SCD or TDT ages 12 to 35 years. Patients will be followed for approximately one year after infusion. Each patient will be asked to participate in CLIMB-131, a long-term follow-up trial.

About the Gene-Editing Process in These Trials

Patients who enroll in these trials will have their own hematopoietic stem and progenitor cells collected from peripheral blood. The patient’s cells will be edited using the CRISPR/Cas9 technology. The edited cells, exa-cel, will then be infused back into the patient as part of an autologous hematopoietic stem cell transplant (HSCT), a process which involves a patient being treated with myeloablative busulfan conditioning. Patients undergoing HSCT may also encounter side effects (ranging from mild to severe) that are unrelated to the administration of exa-cel. Patients will initially be monitored to determine when the edited cells begin to produce mature blood cells, a process known as engraftment. After engraftment, patients will continue to be monitored to track the impact of exa-cel on multiple measures of disease and for safety.

On December 10, 2022 AbbVie (NYSE: ABBV) reported new and updated data across clinical and real-world studies in chronic lymphocytic leukemia (CLL) (Press release, AbbVie, DEC 10, 2022, View Source [SID1234625008]). Presentations featured during the 64th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting and Exposition will include two clinical trials investigating once daily, fixed-duration treatment with IMBRUVICA (ibrutinib) plus VENCLEXTA/VENCLYXTO (venetoclax) (I+V) in adults with CLL and several analyses from real-word data evaluating front-line treatment in CLL.

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!

"As the only Bruton’s Tyrosine Kinase inhibitor (BTKi) studied across many clinical trials, including up to eight years of follow-up data in CLL and small lymphocytic lymphoma (SLL), these latest data add to overall evidence for IMBRUVICA," said James Dean, M.D., Ph.D., global development lead and executive medical director, Pharmacyclics LLC, an AbbVie company. "These findings further inspire our commitment to the continued investigation of IMBRUVICA in the treatment of patients with CLL."

Presentations will include the five-year median follow-up efficacy and safety data from the minimal residual disease (MRD) Cohort of the Phase 2 CAPTIVATE study (Abstract #92)1 and data on MRD kinetics from the randomized, open-label Phase 3 GLOW study (Abstract #93).2 Additionally, new data from three studies evaluating the impact of IMBRUVICA treatment in the real-world setting will be presented (Abstracts #797,#1809, #3132).3,4,5

Five-Year Update from the CAPTIVATE Study Adds to Clinical Data Investigating the Potential of a Fixed-Duration Regimen

The MRD Cohort of the Phase 2 CAPTIVATE (NCT02910583) study evaluated 164 patients age 70 years or younger with previously untreated CLL; those who achieved confirmed undetectable minimal residual disease (uMRD) after completion of I+V fixed-duration treatment were randomly assigned to placebo (PBO) (n=43), or continued IMBRUVICA treatment (n=43).1 For patients with confirmed uMRD, median time on study was 56 months (PBO arm range, 40‒65 months; IMBRUVICA arm range, 25‒68 months); median post-randomization follow-up was 41 months in both arms.1 At four years of follow-up, estimated progression-free survival (PFS) was 88 percent (95 percent Confidence Interval [CI], 74-95, seven progressive disease events) with PBO compared to 95 percent (95 percent CI, 82-99, two progressive disease events) with continued IMBRUVICA treatment.1 Additionally, at year four, patients in the PBO arm of the study achieved an estimated overall survival (OS) rate of 100 percent compared to 98 percent (95 percent CI, 84-99.7) in the IMBRUVICA treatment arm.1

No new atrial fibrillation (AF) or Grade three or higher hemorrhage events occurred in the PBO arm during the three year post-randomization period, and one patient in the IMBRUVICA arm had AF in the second year post-randomization.1 During the three-year post-randomization period, adverse events (AEs) of any grade for patients treated with IMBRUVICA were arthralgia (4/41), hypertension (2/41), neutropenia (1/41) and diarrhea (1/41). No new grade three or higher hemorrhage events occurred in either arm.1

The Data of IMBRUVICA in the Treatment of CLL Through Real-World Studies

An oral presentation (Abstract #797) will report findings comparing time to next treatment (TTNT) in patients with CLL who received first-line treatment with IMBRUVICA or acalabrutinib based on a real-world study utilizing electronic medical records.3

A poster presentation (Abstract #1809) will highlight results from a pooled analysis of the RESONATE-2 (NCT01722487), ECOG1912 (NCT02048813), and iLLUMINATE (NCT02264574) clinical studies investigating the comparison of OS in previously untreated CLL patients treated with IMBRUVICA to that of the available age-matched general population, as well as comparative results of OS in patients treated with IMBRUVICA versus chemotherapy and chemoimmunotherapy.4

Thirdly, the final analysis from the informCLL real-world (RW) registry, which assessed RW outcomes with first-line IMBRUVICA versus chemoimmunotherapy (CIT) in patients with CLL and SLL, will be presented as a poster (Abstract #3132).5 The informCLL registry enrolled 1,459 patients, of whom 59 percent were previously untreated.5 First-line treatment with IMBRUVICA was associated with longer TTNT than with CIT and sustained benefit, with up to four years of follow-up.5 In the IMBRUVICA cohort (n=383), serious adverse events (AEs) occurred in 144 patients (38 percent), most commonly (greater or equal to three percent of patients) pneumonia (six percent) and atrial fibrillation (five percent); AEs led to discontinuation of IMBRUVICA in 135 patients (35 percent), most commonly atrial fibrillation (five percent) and fatigue (three percent). In the CIT cohort (n=363), serious AEs occurred in 85 patients (23 percent), most commonly febrile neutropenia (four percent) and pneumonia (three percent). AEs led to discontinuation of CIT in 61 patients (17 percent), and no single AE term led to discontinuation in three percent or more of patients (most common was anemia, two percent).5 The spectrum and frequency of AEs observed with first-line treatment appeared consistent with data from clinical studies and other RWE studies.5

About IMBRUVICA
IMBRUVICA (ibrutinib) is a once-daily oral medication that is jointly developed and commercialized by Janssen Biotech, Inc. and Pharmacyclics LLC, an AbbVie company. IMBRUVICA blocks the Bruton’s tyrosine kinase (BTK) protein, which is needed by normal and abnormal B cells, including specific cancer cells, to multiply and spread. By blocking BTK, IMBRUVICA may help move abnormal B cells out of their nourishing environments and inhibits their proliferation.6,7,8

IMBRUVICA is approved in more than 100 countries and has been used to treat more than 270,000 patients worldwide. There are more than 50 company-sponsored clinical trials, including 18 Phase 3 studies, over 11 years evaluating the efficacy and safety of IMBRUVICA.

IMBRUVICA was first approved by the U.S. Food and Drug Administration (FDA) in November 2013, and today is indicated for adult patients in six disease areas, including five hematologic cancers. These include indications to treat adults with CLL/SLL with or without 17p deletion (del17p), adults with Waldenström’s macroglobulinemia (WM), adults with previously treated mantle cell lymphoma (MCL)*, adult patients with previously treated marginal zone lymphoma (MZL) who require systemic therapy and have received at least one prior anti-CD20-based therapy*, as well as adult and pediatric patients one year of age and older with previously treated chronic graft versus host disease (cGVHD) after failure of one or more lines of systemic therapy.9

*Accelerated approval was granted for MCL and MZL based on overall response rate. Continued approval for MCL and MZL may be contingent upon verification and description of clinical benefit in confirmatory trials.

For more information, visit www.IMBRUVICA.com.

IMPORTANT SIDE EFFECT INFORMATION

Before taking IMBRUVICA, tell your healthcare provider about all of your medical conditions, including if you:

have had recent surgery or plan to have surgery. Your healthcare provider may stop IMBRUVICA for any planned medical, surgical, or dental procedure.
have bleeding problems
have or had heart rhythm problems, smoke, or have a medical condition that increases your risk of heart disease, such as high blood pressure, high cholesterol, or diabetes
have an infection
have liver problems
are pregnant or plan to become pregnant. IMBRUVICA can harm your unborn baby. If you are able to become pregnant, your healthcare provider will do a pregnancy test before starting treatment with IMBRUVICA. Tell your healthcare provider if you are pregnant or think you may be pregnant during treatment with IMBRUVICA.
Females who are able to become pregnant should use effective birth control (contraception) during treatment with IMBRUVICA and for 1 month after the last dose.
Males with female partners who are able to become pregnant should use effective birth control, such as condoms, during treatment with IMBRUVICA and for 1 month after the last dose.
are breastfeeding or plan to breastfeed. Do not breastfeed during treatment with IMBRUVICA and for 1 week after the last dose.
Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements. Taking IMBRUVICA with certain other medicines may affect how IMBRUVICA works and can cause side effects.

How should I take IMBRUVICA?

Take IMBRUVICA exactly as your healthcare provider tells you to take it.
Take IMBRUVICA 1 time a day at about the same time each day.
IMBRUVICA comes as capsules, tablets, and oral suspension.

If your healthcare provider prescribes IMBRUVICA capsules or tablets:
Swallow IMBRUVICA capsules or tablets whole with a glass of water.
Do not open, break, or chew IMBRUVICA capsules.
Do not cut, crush, or chew IMBRUVICA tablets.
If your healthcare provider prescribes IMBRUVICA oral suspension:
See the detailed Instructions for Use that comes with IMBRUVICA oral suspension for information about the correct way to give a dose to your child. If you have questions about how to give IMBRUVICA oral suspension, talk to your healthcare provider.
Do not use if the carton seal is broken or missing.
If you miss a dose of IMBRUVICA take it as soon as you remember on the same day. Take your next dose of IMBRUVICA at your regular time on the next day. Do not take extra doses of IMBRUVICA to make up for a missed dose.
If you take too much IMBRUVICA call your healthcare provider or go to the nearest hospital emergency room right away.
What should I avoid while taking IMBRUVICA?

You should not drink grapefruit juice, eat grapefruit, or eat Seville oranges (often used in marmalades) during treatment with IMBRUVICA. These products may increase the amount of IMBRUVICA in your blood.
What are the possible side effects of IMBRUVICA?
IMBRUVICA may cause serious side effects, including:

Bleeding problems (hemorrhage) are common during treatment with IMBRUVICA, and can also be serious and may lead to death. Your risk of bleeding may increase if you are also taking a blood thinner medicine. Tell your healthcare provider if you have any signs of bleeding, including: blood in your stools or black stools (looks like tar), pink or brown urine, unexpected bleeding, or bleeding that is severe or that you cannot control, vomit blood or vomit looks like coffee grounds, cough up blood or blood clots, increased bruising, dizziness, weakness, confusion, change in your speech, or a headache that lasts a long time or severe headache.
Infections can happen during treatment with IMBRUVICA. These infections can be serious and may lead to death. Tell your healthcare provider right away if you have fever, chills, weakness, confusion, or other signs or symptoms of an infection during treatment with IMBRUVICA.
Heart problems. Serious heart rhythm problems (ventricular arrhythmias, atrial fibrillation and atrial flutter), heart failure and death have happened in people treated with IMBRUVICA, especially in people who have an infection, an increased risk for heart disease, or have had heart rhythm problems in the past. Your heart function will be checked before and during treatment with IMBRUVICA. Tell your healthcare provider if you get any symptoms of heart problems, such as feeling as if your heart is beating fast and irregular, lightheadedness, dizziness, shortness of breath, swelling of the feet, ankles or legs, chest discomfort, or you faint. If you develop any of these symptoms, your healthcare provider may do tests to check your heart and may change your IMBRUVICA dose.
High blood pressure (hypertension). New or worsening high blood pressure has happened in people treated with IMBRUVICA. Your healthcare provider may start you on blood pressure medicine or change current medicines to treat your blood pressure.
Decrease in blood cell counts. Decreased blood counts (white blood cells, platelets, and red blood cells) are common with IMBRUVICA, but can also be severe. Your healthcare provider should do monthly blood tests to check your blood counts.
Second primary cancers. New cancers have happened during treatment with IMBRUVICA, including cancers of the skin or other organs.
Tumor lysis syndrome (TLS). TLS is caused by the fast breakdown of cancer cells. TLS can cause kidney failure and the need for dialysis treatment, abnormal heart rhythm, seizure, and sometimes death. Your healthcare provider may do blood tests to check you for TLS.
The most common side effects of IMBRUVICA in adults with B-cell malignancies (MCL, CLL/SLL, WM and MZL) include:

· diarrhea

· tiredness

· muscle and bone pain

· rash

· bruising

The most common side effects of IMBRUVICA in adults or children 1 year of age and older with cGVHD include:

· tiredness

· low red blood cell count (anemia)

· bruising

· diarrhea

· low platelet count

· muscle and joint pain

· fever

· muscle spasms

· mouth sores (stomatitis)

· bleeding

· nausea

· stomach pain

· pneumonia

· headache

Diarrhea is a common side effect in people who take IMBRUVICA. Drink plenty of fluids during treatment with IMBRUVICA to help reduce your risk of losing too much fluid (dehydration) due to diarrhea. Tell your healthcare provider if you have diarrhea that does not go away.

These are not all the possible side effects of IMBRUVICA. 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 IMBRUVICA
Medicines are sometimes prescribed for purposes other than those listed in a Patient Information leaflet. Do not use IMBRUVICA for a condition for which it was not prescribed. Do not give IMBRUVICA to other people, even if they have the same symptoms that you have. It may harm them. You can ask your pharmacist or healthcare provider for information about IMBRUVICA that is written for health professionals.

Please click here for full Prescribing Information.

About VENCLYXTA (venetoclax)
VENCLYXTA (venetoclax) is a first-in-class medicine that selectively binds and inhibits the B-cell lymphoma-2 (BCL-2) protein. In some blood cancers, BCL-2 prevents cancer cells from undergoing their natural death or self-destruction process, called apoptosis. VENCLYXTA targets the BCL-2 protein and works to help restore the process of apoptosis.

VENCLYXTA is being developed by AbbVie and Roche. It is jointly commercialized by AbbVie and Genentech, a member of the Roche Group, in the U.S. and by AbbVie outside of the U.S. Together, the companies are committed to BCL-2 research and to studying venetoclax in clinical trials across several blood and other cancers. Venetoclax is approved in more than 80 countries, including the U.S.

Approved Uses of VENCLEXTA

VENCLEXTA is a prescription medicine used:

to treat adults with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL).
in combination with azacitidine, or decitabine, or low-dose cytarabine to treat adults with
newly diagnosed acute myeloid leukemia (AML) who:
are 75 years of age or older, or
have other medical conditions that prevent the use of standard chemotherapy.
It is not known if VENCLEXTA is safe and effective in children.

Important Safety Information

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

VENCLEXTA can cause serious side effects, including:

Tumor lysis syndrome (TLS). TLS is caused by the fast breakdown of cancer cells. TLS can cause kidney failure, the need for dialysis treatment, and may lead to death. Your healthcare provider will do tests to check your risk of getting TLS before you start taking VENCLEXTA. You will receive other medicines before starting and during treatment with VENCLEXTA to help reduce your risk of TLS.

You may also need to receive intravenous (IV) fluids into your vein. Your healthcare provider will do blood tests to check for TLS when you first start treatment and during treatment with VENCLEXTA.

It is important to keep your appointments for blood tests. Tell your healthcare provider right away if you have any symptoms of TLS during treatment with VENCLEXTA, including fever, chills, nausea, vomiting, confusion, shortness of breath, seizures, irregular heartbeat, dark or cloudy urine, unusual tiredness, or muscle or joint pain.

Drink plenty of water during treatment with VENCLEXTA to help reduce your risk of getting TLS.

Drink 6 to 8 glasses (about 56 ounces total) of water each day, starting 2 days before your first dose, on the day of your first dose of VENCLEXTA, and each time your dose is increased.

Your healthcare provider may delay, decrease your dose, or stop treatment with VENCLEXTA if you have side effects. When restarting VENCLEXTA after stopping for 1 week or longer, your healthcare provider may again check for your risk of TLS and change your dose.

Who should not take VENCLEXTA?

Certain medicines must not be taken when you first start taking VENCLEXTA and while your dose is being slowly increased because of the risk of increased TLS.

Tell your healthcare provider about all the medicines you take, including prescription and over-the- counter medicines, vitamins, and herbal supplements. VENCLEXTA and other medicines may affect each other causing serious side effects.
Do not start new medicines during treatment with VENCLEXTA without first talking with your healthcare provider.
Before taking VENCLEXTA, tell your healthcare provider about all of your medical conditions, including if you:

have kidney or liver problems.
have problems with your body salts or electrolytes, such as potassium, phosphorus, or calcium.
have a history of high uric acid levels in your blood or gout.
are scheduled to receive a vaccine. You should not receive a "live vaccine" before, during, or after treatment with VENCLEXTA, until your healthcare provider tells you it is okay. If you are not sure about the type of immunization or vaccine, ask your healthcare provider. These vaccines may not be safe or may not work as well during treatment with VENCLEXTA.
are pregnant or plan to become pregnant. VENCLEXTA may harm your unborn baby. If you are able to become pregnant, your healthcare provider should do a pregnancy test before you start treatment with VENCLEXTA, and you should use effective birth control during treatment and for 30 days after the last dose of VENCLEXTA. If you become pregnant or think you are pregnant, tell your healthcare provider right away.
are breastfeeding or plan to breastfeed. It is not known if VENCLEXTA passes into your breast milk.
Do not breastfeed during treatment with VENCLEXTA and for 1 week after the last dose.
What should I avoid while taking VENCLEXTA?

You should not drink grapefruit juice or eat grapefruit, Seville oranges (often used in marmalades), or starfruit while you are taking VENCLEXTA. These products may increase the amount of VENCLEXTA in your blood.

What are the possible side effects of VENCLEXTA?

VENCLEXTA can cause serious side effects, including:

Low white blood cell counts (neutropenia). Low white blood cell counts are common with VENCLEXTA, but can also be severe. Your healthcare provider will do blood tests to check your blood counts during treatment with VENCLEXTA and may pause dosing.
Infections. Death and serious infections such as pneumonia and blood infection (sepsis) have happened during treatment with VENCLEXTA. Your healthcare provider will closely monitor and treat you right away if you have a fever or any signs of infection during treatment with VENCLEXTA.
Tell your healthcare provider right away if you have a fever or any signs of an infection during treatment with VENCLEXTA.

The most common side effects of VENCLEXTA when used in combination with obinutuzumab or rituximab or alone in people with CLL or SLL include low white blood cell counts; low platelet counts; low red blood cell counts; diarrhea; nausea; upper respiratory tract infection; cough; muscle and joint pain; tiredness; and swelling of your arms, legs, hands, and feet.

The most common side effects of VENCLEXTA in combination with azacitidine or decitabine or low-dose cytarabine in people with AML include nausea; diarrhea; low platelet count; constipation; low white blood cell count; fever with low white blood cell count; tiredness; vomiting; swelling of arms, legs, hands, or feet; fever; infection in lungs; shortness of breath; bleeding; low red blood cell count; rash; stomach (abdominal) pain; infection in your blood; muscle and joint pain; dizziness; cough; sore throat; and low blood pressure.

VENCLEXTA may cause fertility problems in males. This may affect your ability to father a child. Talk to your healthcare provider if you have concerns about fertility.

These are not all the possible side effects of VENCLEXTA. Call your doctor for medical advice about side effects.

You are encouraged to report side effects of prescription drugs to the FDA. Visit www.fda.gov/medwatch or call 1-800-FDA-1088.

If you cannot afford your medication, contact genentech-access.com/patient/brands/venclexta for assistance.