Scenic Biotech and Genentech expand their Genetic Modifier Partnership

On May 19, 2021 Scenic Biotech BV ("Scenic"), a pioneer in the discovery of genetic modifiers to enable the development of disease modifying therapeutics for rare genetic disorders and other devastating illnesses, reported that it has entered into a multi-year strategic collaboration with Genentech, a member of the Roche Group, to discover, develop and commercialize novel therapeutics that target genetic modifiers (Press release, Scenic Biotech, MAY 19, 2021, View Source [SID1234580249]).

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Genetic modifiers are genes that counteract the effect of a disease-causing gene. They may explain why some people with genetic mutations linked to severe disease end up having only mild or no symptoms. Also known as disease suppressors, genetic modifiers therefore positively influence the severity of disease and act as a ‘natural form of protection’. Their discovery is leading to a completely new class of drug targets.

Under the terms of the agreement, Scenic will utilize its Cell-Seq platform and its data warehouse of genetic modifiers to identify drug targets in multiple therapeutic areas. The collaboration enables Genentech to select multiple targets for further development with an option to extend the collaboration. Scenic will receive an undisclosed upfront payment and is eligible to receive additional target selection fees for drug targets taken forward by Genentech. In addition, Scenic is eligible for success-based payments for each target based on achievement of certain predetermined milestones, as well as royalties on sales of certain products resulting from the collaboration. Total deal value could exceed US $375M.

Scenic has built an extensive proprietary data warehouse of genetic modifiers and its Cell-Seq platform enables the development of potential disease modifying therapeutics for devastating diseases with an in-house focus on inherited rare diseases and immuno-oncology/inflammation.
The Company was founded in 2017 as a spin-out of the Netherlands Cancer Institute, and Oxford University and recently appointed Oscar Izeboud, PhD as its Chief Executive Officer.

Dr Sebastian Nijman, Co-founder and CSO of Scenic Biotech said:
"Genentech is the pioneer in innovative biotech and has world leading research and development capabilities. Scenic is a science-driven company and having Genentech as our first major industry partner is a great validation of our technology and by working together it will extend the utility of our platform beyond our current therapeutic areas of interest. The collaboration also brings significant strategic value for Scenic as it enables us to realise the potential of our genetic modifier expertise alongside independently advancing our own programs towards clinical development."

Nevada’s Drug Price Transparency Bill Up for Permanent Funding

On May 19, 2021 Nevada reported that Senate Finance Committee considered a $780,000 fiscal note from the Department of Health and Human Services (HHS) to fund a measure under SB380 that aims to transfer the existing state drug pricing database to the Enterprise Information Technology Services Division, where it would be managed by a pharmacist, with support from a management analyst (Press release, EVERSANA, MAY 19, 2021, View Source [SID1234580248]).

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Expanding on two bills from 2017 and 2019 that targeted price increase for diabetes and asthma drugs, respectively, SB380 would require manufacturers of all drugs, regardless of the disease they target, that exceed a $40 list prices for a course of therapy and saw a 10% increase during the previous calendar year to report certain costs and profits associated with the production of the drugs.

Further, for drugs with a list price exceeding $40 for a course of therapy, the bill would have prescription drug wholesalers report to the state minimum and maximum list prices of the drug over the last year and the aggregate amount of rebates negotiated with drug companies, manufacturers, and pharmacy benefit managers (PBMs).

The Finance Committee and HHS considered using penalties and fees collected from the diabetes and asthma programs when companies failed to meet reporting requirements; however, these funds were initially planned to go toward diabetes and asthma education programs. For SB380 sponsor Senator Julia Ratti, the use of these penalties and fees to fund management of the transparency database is a good start, but a more concrete solution is necessary.

Ratti commented, "The Department of Health and Human Services has been doing yeoman’s work to fulfill the NRS around transparency reporting…but the resources haven’t necessarily been there to do the robust analysis and the robust reporting with the data we have available. With this bill, we requested the unsolicited fiscal note to really look at, what would it cost to implement our drug transparency program in a sustainable way where we’re not taking a little bit of somebody’s time over here and a little bit of somebody’s time over there."

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Teneobio’s Clinical Candidate, TNB-409, is a Selective IL-2 Receptor Bispecific Agonist for the Treatment of Solid Tumors

On May 19, 2021 Teneobio, Inc., a clinical stage biotech company focused on the discovery and development of novel multi-specific biotherapeutic antibodies, reported the publication of its bispecific human heavy chain only antibody (TNB-409) with selective IL-2βγ receptor heterodimeric agonist activity in Scientific Reports (www.nature.com/articles/s41598-021-90096-8) (Press release, TeneoBio, MAY 19, 2021, View Source;utm_medium=rss&utm_campaign=teneobio-announces-tnb-409-is-a-selective-il-2-receptor-bispecific-agonist-for-the-reatment-of-solid-tumors [SID1234580247]).

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By circumventing signaling through the α chain of the IL-2 receptor, TNB-409 minimizes Treg activation and retains robust immunostimulatory activity of T and NK cells in vitro and in vivo in monkey studies. TNB-409’s extended half-life and demonstrable safety in monkeys potentially confers a better therapeutic window for the treatment of solid tumors. TNB-409 is poised to enter phase 1 clinical studies in Q2 of 2022.

Katherine Harris, VP of Discovery at Teneobio added, "TNB-409 couples the beneficial aspects of IL-2 with Fc-mediated extended half-life, while avoiding the undesirable side effects associated with binding to IL-2Rα. TNB-409 not only achieves the desired biological activity of stimulating T and NK effector cells, moreover, it validates the applicability of Teneobio’s human single domain platform of multispecifics to target other therapeutically relevant receptor signaling pathways."

Exscientia announces multi-target, AI-driven drug discovery collaboration with Bristol Myers Squibb

On May 19, 2021 Exscientia, the clinical stage, Artificial Intelligence (AI)-driven pharmatech company, reported that it has entered into a collaboration agreement with Bristol-Myers Squibb Company (NYSE: BMY) (Press release, Exscientia, MAY 19, 2021, View Source [SID1234580246]). This expanded collaboration has the potential to add to the Bristol Myers Squibb drug pipeline whilst enhancing Exscientia’s portfolio of shared assets. The collaboration will use AI to accelerate the discovery of small molecule therapeutic drug candidates in multiple therapeutic areas, including oncology & immunology. The agreement includes up to $50 million in upfront funding, up to $125 million in near to mid-term potential milestones, and additional clinical, regulatory and commercial payments that take the potential value of the deal beyond $1.2 billion. Exscientia will also receive tiered royalties on net sales of any marketed drug products resulting from the collaboration.

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This expanded collaboration builds upon Exscientia’s existing collaboration with Bristol Myers Squibb that was initiated in 2019 with Celgene prior to Celgene’s acquisition by Bristol Myers Squibb. Exscientia will take responsibility for AI-design and experimental work necessary to discover drug candidates associated with this collaboration for Bristol Myers Squibb. Molecules will be designed using Exscientia’s AI-driven drug discovery platform, which delivers optimized compounds fulfilling complex design goals faster and more effectively than traditional drug discovery.

Andrew Hopkins, CEO of Exscientia, commented, "We are proud that Bristol Myers Squibb wants to build on our work together with this expanded collaboration and believe it speaks to the strength and promise of Exscientia’s AI technologies and drug discovery expertise. We’re excited to work with such an experienced collaborator as Bristol Myers Squibb to develop the best possible medicines for patients."

Rupert Vessey, President of Research & Early Development at Bristol Myers Squibb said, "We have been pleased with Exscientia’s work in tackling a number of distinct projects for Bristol Myers Squibb. Exscientia’s application of AI technologies is proving capable of generating best-in-class molecules while also reducing discovery times. Rapid discovery of molecules that can enter the clinic in a timely manner could positively impact our work in discovering treatments for areas of unmet medical need"

Exscientia has already built a strong track record for its drug discovery platform, being the first company to advance AI-designed small molecule drug candidates into clinical studies. In addition to Bristol Myers Squibb, Exscientia has previously entered collaborations with major pharmaceutical companies including Bayer, Sanofi, and Dainippon Sumitomo, multiple emerging biotech companies and the Gates Foundation, demonstrating Exscientia’s reputation as the collaborator of choice for high-value AI-driven drug discovery. The company currently has more than a dozen partnered or wholly owned drugs in development. Exscientia recently secured a $525 million Series D investment, led by Softbank, to further fund expansion of its technology capabilities and proprietary drug pipeline.

AbbVie to Showcase Breadth of Oncology Portfolio and Pipeline at the 2021 ASCO and EHA Annual Congresses

On May 19, 2021 AbbVie (NYSE: ABBV) reported that it will present results from 43 abstracts across 12 types of cancer during the upcoming virtual American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting (June 4-8) and the virtual European Hematology Association (EHA) (Free EHA Whitepaper) congress (June 9-17) (Press release, AbbVie, MAY 19, 2021, View Source [SID1234580245]).

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"We are advancing discovery and innovation to improve on the standards of care for blood cancer treatment," said Mohamed Zaki, M.D., Ph.D., vice president and global head of oncology development, AbbVie. "We look forward to showcasing research from our expanding oncology portfolio at the ASCO (Free ASCO Whitepaper) 2021 annual meeting and EHA (Free EHA Whitepaper) 2021 congress."

Presentations include nine oral presentations (two at ASCO (Free ASCO Whitepaper) and seven at EHA (Free EHA Whitepaper)) and 32 poster presentations (13 at ASCO (Free ASCO Whitepaper) and 19 at EHA (Free EHA Whitepaper)).

At ASCO (Free ASCO Whitepaper), AbbVie will present data from its Phase 2 CAPTIVATE study evaluating complete response (CR) and progression-free survival (PFS) among other study metrics in previously untreated patients with chronic lymphocytic leukemia (CLL)/small lymphocytic leukemia (SLL) who received an ibrutinib (IMBRUVICA) + venetoclax (VENCLEXTA/VENCLYXTO) combination regimen.

In addition, during the congresses, AbbVie will present results from several studies, including those that evaluate venetoclax in several combination regimens and in multiple hematological malignancies. These include a four-year follow-up of the CLL14 trial of venetoclax plus obinutuzumab in patients with previously untreated CLL, long-term results from the MURANO trial of venetoclax plus rituximab in relapsed/refractory CLL, and additional post-hoc analyses of the VIALE-A trial of venetoclax in combination with azacitidine in patients with acute myeloid leukemia (AML). An up-to seven-year follow up of the ibrutinib RESONATE-2 study in first-line CLL will also be presented and add to robust long-term efficacy and safety data for this therapy.

Details about presentations are as follows:

ASCO 2021 Abstracts

Abstract

Presentation Details

All Times in CT

Ibrutinib

Up to Seven Years of Follow-up in the
RESONATE-2 Study of First-line Ibrutinib
Treatment for Patients with Chronic L
ymphocytic Leukemia (CLL)

Session: Hematologic Malignancies—Lymphoma and Chronic Lymphocytic Leukemia

Friday, June 4

8:00 a.m. (CT)

Poster Discussion

Phase 1/2 Study of Cirmtuzumab and
Ibrutinib in Mantle Cell Lymphoma (MCL) or
Chronic Lymphocytic Leukemia (CLL)

Session: Hematologic Malignancies—Lymphoma and Chronic Lymphocytic Leukemia

Friday, June 4

8:00 a.m. (CT)

Poster Discussion

Randomized, Double-blind, Placebo-
controlled Phase Three study of Ibrutinib Plus
Rituximab in Patients with Previously
Untreated Marginal Zone Lymphoma (MZL).

Session: Hematologic Malignancies—Lymphoma and Chronic Lymphocytic Leukemia

Friday, June 4

8:00 a.m. (CT)

Poster

Fixed-Duration (FD) First-line Treatment (tx)
with Ibrutinib (I) Plus Venetoclax (V) for
Chronic Lymphocytic Leukemia (CLL)/small
Lymphocytic Lymphoma (SLL): Primary
Analysis of the FD Cohort of the Phase 2
CAPTIVATE study

Session: Hematologic Malignancies—Lymphoma and Chronic Lymphocytic Leukemia

Monday, June 7

10:30 a.m. to 1:30 p.m. (CT)

Oral Presentation

Venetoclax

Measurable Residual Disease Response in
Acute Myeloid Leukemia Treated with
Venetoclax and Azacitidine

Session: Hematologic Malignancies—Leukemia, Myelodysplastic Syndromes, and Allotransplant

Friday, June 4

8:00 (CT)

Poster

Venetoclax and Azacitidine Combination in
Chemotherapy Ineligible Untreated Patients
with Therapy-related Myeloid Neoplasms,
Antecedent Myelodysplastic Syndromes or
Myelodysplastic/Myeloproliferative
Neoplasms

Session: Hematologic Malignancies—Leukemia, Myelodysplastic Syndromes, and Allotransplant

Friday, June 4

8:00 (CT)

Poster

Phase 3 VERONA Study of Venetoclax with
Azacitidine to Assess Change in Complete
Remission and Overall Survival in Treatment-
Naïve Higher-Risk Myelodysplastic
Syndromes

Session: Hematologic Malignancies—Leukemia, Myelodysplastic Syndromes, and Allotransplant

Friday, June 4

8:00 a.m. (CT)

Poster

Comparison of Dose Modification Strategies
to Address Expected Hematologic Toxicities
in Treatment-Naïve Higher-Risk (HR) MDS
Patients Treated with Venetoclax +
Azacitidine

Session: Hematologic Malignancies—Leukemia, Myelodysplastic Syndromes, and Allotransplant

Friday, June 4

8:00 a.m. (CT)

Poster

Randomized, Phase III Study of Early
Intervention with Venetoclax and
Obinutuzumab Versus Delayed Therapy with
Venetoclax and Obinutuzumab in Newly
Diagnosed Asymptomatic High-Risk Patients
with Chronic Lymphocytic Leukemia/Small
Lymphocytic Lymphoma (CLL/SLL): Evolve
CLL/SLL Study (SWOG S1925; NCT#04269902)

Session: Hematologic Malignancies – Lymphoma and Chronic Lymphocytic Leukemia

Friday, June 4

8:00 a.m. (CT)

Poster

Polatuzumab Vedotin + Obinutuzumab +
Venetoclax in Patients with
Relapsed/refractory (R/R) Follicular
Lymphoma (FL): Primary Analysis of a Phase
1b/2 Trial

Session: Hematologic Malignancies – Lymphoma and Chronic Lymphocytic Leukemia

Friday, June 4

8:00 a.m. (CT)

Poster

Epcoritamab*

Subcutaneous Epcoritamab in Patients With
Relapsed/Refractory B-Cell Non-Hodgkin
Lymphoma: Safety Profile and Antitumor
Activity

Session: Hematologic Malignancies – Lymphoma and Chronic Lymphocytic Leukemia

Friday, June 4

8:00 a.m. (CT)

Poster

Phase 3 Trial (GCT3013-05) of Epcoritamab
Versus Standard of Care in Patients With
Relapsed or Refractory Diffuse Large B-Cell
Lymphoma (DLBCL)

Session: Hematologic Malignancies—Lymphoma and Chronic Lymphocytic Leukemia

Friday, June 4

8:00 a.m. (CT)

Poster

ABBV-155

A First-in-Human Study of Mirzotamab
Clezutoclax as Monotherapy and in
Combination with Taxane Therapy in
Relapsed/Refractory Solid Tumors: Dose
Escalation Results

Session: Developmental Therapeutics—Molecularly Targeted Agents and Tumor Biology

Friday, June 4

8:00 a.m. (CT)

Poster

ABBV-184

Phase 1 First-in-human Study of ABBV-184
Monotherapy in Adult Patients with Previously
Treated Acute Myeloid Leukemia or Non
-small Cell Lung Cancer

Session: Developmental Therapeutics—Immunotherapy

Friday, June 4

8:00 a.m. (CT)

Poster

The ASCO (Free ASCO Whitepaper) 2021 Annual Meeting abstracts are available at: View Source

* Epcoritamab is being co-developed by Genmab and AbbVie as part of the companies’ broad oncology collaboration.

EHA 2021 Abstracts

Abstract

Presentation Details

All Times in CEST

Ibrutinib

Ibrutinib vs Placebo in Combination with
Corticosteriods in Patients with New-Onset
Chronic Graft-Versus-Host Disease (cGVHD):
Results from the Randomized, Double-Blind
Phase 3 iNTEGRATE Study

Session: Stem Cell Transplantation – cGVHD

Friday, June 11

9:00 a.m. (CEST)

Oral Presentation

Primary Analysis of the Fixed-Duration Cohort
from the Phase 2 CAPTIVATE Study of First-
Line Ibrutinib + Venetoclax for Chronic
Lymphocytic Leukemia/Small Lymphocytic
Lymphoma

Session: Clinical Trials with Targeted Therapies in CLL

Friday, June 11

9:00 a.m. (CEST)

Oral Presentation

Real-World Application of National
Comprehensive Cancer Network Clinical
Practice Guidelines in Oncology (NCCN
Guidelines) for CLL/SLL from the informCLL
Registry

Session: Chronic Lymphocytic Leukemia and Related-Disorders – Clinical

Friday, June 11

Session: 9:00 a.m. (CEST)

Poster

Effectiveness and Safety of Ibrutinib in Chronic
Lymphocytic Leukemia (CLL) and Mantle Cell
Lymphoma (MCL) in Belgian Routine Clinical
Practice with a 3-Year Follow-up

Session: Chronic Lymphocytic Leukemia and Related-Disorders – Clinical

Friday, June 11

Session: 9:00 a.m. (CEST)

Poster

Ibrutinib, Bendamustine, Rituximab for
Relapsed and Refractory Aggressive B Cell
Lymphoma – Final Analysis of Phase II Clinical
Trial

Session: Aggressive Non-Hodgkin Lymphoma – Clinical

Friday, June 11

Session: 9:00 a.m. (CEST)

Poster

Ibrutinib Treatment in the First-Line Setting for
Patients with Chronic Lymphocytic Leukemia:
Up to 7 Years of Follow-up in the Resonate-2
Study

Session: Chronic Lymphocytic Leukemia and Related-Disorders – Clinical

Friday, June 11

9:00 a.m. (CEST)

Poster

Ibrutinib Plus Rituximab (IR) vs Placebo Plus
Rituximab (R) for Waldenström’s
Macroglobulinemia (WM): Final Analysis After
Five Years of Follow-up from the Randomized
Phar 3 INNOVATE Study

Session: Indolent and Mantle-Cell Non-Hodgkins Lymphoma – Clinical

Friday, June 11

9:00 a.m. (CEST)

Poster

Preliminary Clinical Data from a Phase 1B
Study of Mavorixafor and Ibrutinib in Patients
with Waldenström’s Macroglobulinemia with
MYD88 and CXCR4 Mutations

Session: Indolent and Mantle-cell Non-Hodgkin Lymphoma – Clinical

Friday, June 11

9:00 a.m. (CEST)

Poster

Role of Maintenance Rituximab (MR) After
First-Line (1L) Bendamustine + Rituximab (BR)
or R-Chop in Patients (PTS) With Mantle Cell
Lymphoma (MCL) From a Large US Real-
World (RW) Cohort

Session: Indolent and Mantle-Cell Non-Hodgkins Lymphoma – Clinical
Friday, June 11

9:00 (CEST)

Poster

Real-World Treatment Patterns and Outcomes
of 3455 Previously Untreated Mantle Cell
Lymphoma Patients in U.S. Routine Clinical
Practice

Session: Indolent and Mantle-Cell Non-Hodgkin Lymphoma

Friday, June 11

9:00 (CEST)

Poster

Venetoclax

Efficacy and Safety of Venetoclax in
Combination with Gilteritinib for
Relapsed/Refractory FLT3-Mutated Acute
Myeloid Leukemia: Updated Analyses of a
Phase 1b Study

Session: Developments in AML therapy

Friday, June 11

9:00 a.m. (CEST)

Oral Presentation

Measurable Residual Disease Response in
Acute Myeloid Leukemia Treated with
Venetoclax and Azacitidine

Session: Developments in AML therapy

Friday, June 11

9:00 a.m. (CEST)

Oral Presentation

Venetoclax-Obinutuzumab for Previously
Untreated Chronic Lymphocytic Leukemia: 4-
Year Follow-up Analysis of the Randomized
CLL14 Study

Session: Clinical Trials with Targeted Therapies in CLL

Friday, June 11

9:00 a.m. (CEST)

Oral Presentation

Genetic Markers and Outcome in Front Line Obinutuzumab Plus Chlorambucil or Venetoclax – Updated Analysis of the CLL14
Trial

Session: New Biological and Translational Insights in CLL

Friday, June 11

9:00 a.m. (CEST)

Oral Presentation

Primary Analysis of the Fixed-Duration Cohort
From the Phase 2 CAPTIVATE Study of First-
Line Ibrutinib + Venetoclax for Chronic
Lymphocytic Leukemia/Small Lymphocytic
Leukemia

Session: Chronic Lymphoid Malignancies

Friday, June 11

9:00 a.m. (CEST)

Oral Presentation

French Venetoclax Observational Study
(VERONE): Real-world Study of Venetoclax
Monotherapy for Chronic Lymphocytic
Leukemia (CLL) in France

Session: Chronic lymphocytic leukemia and related disorders – Clinical

Friday, June 11

9:00 a.m. (CEST)

Poster

Safety and Effectiveness of Venetoclax in
Combination with Rituximab in Elderly Patients
with Relapsed/Refractory CLL Treated Under
Real-Life Conditions – Data from the
Observational Study Verve

Session: Chronic Lymphocytic Leukemia and Related-Disorders — Clinical

Friday, June 11

9:00 a.m. (CEST)

Poster

Updated Safety and Efficacy of Venetoclax in
Combination with Azacitidine for the Treatment
of Patients with Treatment-Naïve Higher-Risk Myelodysplastic Syndromes: Phase 1B Results

Session: Myelodysplastic Syndromes – Clinical

Friday, June 11

9:00 a.m. (CEST)

Poster

Comparison of Dose Modification Strategies to
Address Expected Hematologic Toxicities in
Treatment-Naïve Higher-Risk (HR)
MDS Patients Treated with Venetoclax + Azacitidine

Session: Myelodysplastic Syndromes – Clinical

Friday, June 11

9:00 a.m. (CEST)

Poster

Venetoclax and Azacitidine Combination in
Chemotherapy Ineligible Untreated Patients
with Therapy-related Myeloid Neoplasms,
Antecedent Myelodysplastic Syndromes or Myelodysplastic/Myeloproliferative Neoplasms

Session: Myelodysplastic syndromes – Clinical

Friday, June 11

9:00 a.m. (CEST)

Poster

Relationship Between Venetoclax Exposure
and Post-Remission Cytopenias in Subject with Treatment-Naïve Acute Myeloid Leukemia
Treated with Venetoclax Plus Azacitidine in the
Viale-A Study

Session: Acute Myeloid Leukemia – Clinical

Friday, June 11

9:00 a.m. (CEST)

Poster

Venetoclax-Obinutuzumab Modulates Clonal
Growth: Results of a Population-based Minimal
Residual Disease Model from the Randomized
CLL14 Study

Session: Chronic Lymphocytic Leukemia and Related Disorders – Clinical

Friday, June 11

9:00 a.m. (CEST)

Poster

Impact of Unfavorable Genetics on Minimal
Residual Disease (MRD) Response to Venetoclax+Rituximab Retreatment in
Relapsed or Refractory Chronic Lymphocytic
Leukemia (R/R CLL): Phase 3 Murano
Substudy

Session: Chronic lymphocytic leukemia and Related Disorders – Biology & Translational Research

Friday, June 11

9:00 a.m. (CEST)

Poster

Assessing Time to Deterioration in HRQoL in
Patients with Multiple Myeloma Using
Venetoclax in Combination with Bortezomib
and Dexamethasone Compared with Patients
Using Bortezomib and Dexamethasone

Session: Myeloma and Other Monoclonal Gammopathies – Clinical

Friday, June 11

9:00 a.m. (CEST)

Poster

Cytopenia Management in the Phase 3 VIALE-
C Study of Venetoclax Plus Low Dose
Cytarabine for Patients With Newly Diagnosed
Acute Myeloid Leukemia Ineligible for Intensive Chemotherapy

Session: Acute Myeloid Leukemia – Clinical

Friday, June 11

9:00 a.m. (CEST)

Poster

Real World Treatment Patterns and Clinical
Outcomes in Unfit Patients with AML Receiving
First Line Systemic Treatment or Best
Supportive Care (CURRENT). A Belgian
Subanalysis

Acute Myeloid Leukemia – Clinical

Abstract publication only

A Retrospective Analysis of Clinical Outcomes of Patients with Chronic Lymphocytic Leukemia
(CLL) Treated with Venetoclax in the Real-life
Setting in Spain (VENARES)

Chronic Lymphocytic Leukemia and Related-Disorders – Clinical

Abstract publication only

Navitoclax

Navitoclax and Ruxolitinib for Patients with
Myelofibrosis and JAK Inhibitor Experience: Response Duration in Phase 2 Study

Session: Myeloproliferative Neoplasms – Clinical

Friday, June 11

9:00 a.m. (CEST)

Poster

The EHA (Free EHA Whitepaper) 2021 Congress abstracts are available at: View Source

About Ibrutinib (IMBRUVICA)
IMBRUVICA (ibrutinib) is a once-daily, first-in-class BTK inhibitor that is administered orally, and is jointly developed and commercialized by Pharmacyclics, LLC, an AbbVie Company, and Janssen Biotech, Inc. (Janssen). The BTK protein sends important signals that tell B cells to mature and produce antibodies. BTK signaling is needed by specific cancer cells to multiply and spread.1,2 By blocking BTK, IMBRUVICA may help move abnormal B cells out of their nourishing environments in the lymph nodes, bone marrow, and other organs.3

Since its launch in 2013, IMBRUVICA has received 11 FDA approvals across six disease areas: chronic lymphocytic leukemia (CLL) with or without 17p deletion (del17p); small lymphocytic lymphoma (SLL) with or without del17p; Waldenström macroglobulinemia; previously-treated patients with mantle cell lymphoma (MCL)*; previously-treated patients with marginal zone lymphoma (MZL) who require systemic therapy and have received at least one prior anti-CD20-based therapy* – and previously-treated patients with chronic graft-versus-host disease (cGVHD) after failure of one or more lines of systemic therapy.4

IMBRUVICA is now approved in 101 countries and has been used to treat more than 200,000 patients worldwide across its approved indications. IMBRUVICA is the only FDA-approved medicine in WM and cGVHD. IMBRUVICA has been granted four Breakthrough Therapy Designations from the U.S. FDA. This designation is intended to expedite the development and review of a potential new drug for serious or life-threatening diseases. IMBRUVICA was one of the first medicines to receive FDA approval via the Breakthrough Therapy Designation pathway.

Since 2019, the National Comprehensive Cancer Network (NCCN), a not-for-profit alliance of 28 leading cancer centers devoted to patient care, research, and education, recommends ibrutinib (IMBRUVICA) as a preferred regimen for the initial treatment of CLL/SLL and has Category 1 treatment status for treatment-naïve patients without deletion 17p. In January 2020, the NCCN Guidelines were updated to elevate IMBRUVICA with or without rituximab from other recommended regimens to a preferred regimen for the treatment of relapsed/refractory MCL, regardless of duration of response to prior chemoimmunotherapy. As of September 2020, the NCCN guidelines were updated to reflect IMBRUVICA with or without rituximab as the only Category 1 preferred regimen for both untreated and previously treated WM patients.
IMBRUVICA is being studied alone and in combination with other treatments in several blood and solid tumor cancers and other serious illnesses. IMBRUVICA is the most comprehensively studied BTK inhibitor, with more than 150 ongoing clinical trials. There are approximately 30 ongoing company-sponsored trials, 14 of which are in Phase 3, and more than 100 investigator-sponsored trials and external collaborations that are active around the world. For more information, visit www.IMBRUVICA.com.

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

Important Side Effect Information5

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.
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.
Take IMBRUVICA at about the same time each day.
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.
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.
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 increased risk for heart disease, have an infection, or who have had heart rhythm problems in the past. 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 a test to check your heart (ECG) 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.
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 with cGVHD include:

tiredness
bruising
diarrhea
mouth sores (stomatitis)
muscle spasms
nausea
pneumonia
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 VENCLEXTA/VENCLYXTO (venetoclax)

VENCLEXTA/VENCLYXTO (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. VENCLXEXTA/VENCLYXTO targets the BCL-2 protein and works to help restore the process of apoptosis.

VENCLEXTA/VENCLYXTO 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 cancers. Venetoclax is approved in more than 80 countries, including the U.S.

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 at least 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 drug 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.

The full U.S. prescribing information, including Medication Guide, for VENCLEXTA can be found here.

Indication and Important VENCLYXTO (venetoclax) EU Safety Information7
Indication

Venclyxto in combination with obinutuzumab is indicated for the treatment of adult patients with previously untreated chronic lymphocytic leukaemia (CLL).

Venclyxto in combination with rituximab is indicated for the treatment of adult patients with CLL who have received at least one prior therapy.

Venclyxto monotherapy is indicated for the treatment of CLL:

In the presence of 17p deletion or TP53 mutation in adult patients who are unsuitable for or have failed a B-cell receptor pathway inhibitor, or
In the absence of 17p deletion or TP53 mutation in adult patients who have failed both chemoimmunotherapy and a B-cell receptor pathway inhibitor.
Contraindications
Hypersensitivity to the active substance or to any of the excipients is contraindicated. Concomitant use of strong CYP3A inhibitors at initiation and during the dose-titration phase due to increased risk for tumor lysis syndrome (TLS). Concomitant use of preparations containing St. John’s wort as VENCLYXTO efficacy may be reduced.

Special Warnings & Precautions for Use
TLS, including fatal events, has occurred in patients with previously treated CLL with high tumour burden when treated with VENCLYXTO. VENCLYXTO poses a risk for TLS in the initial 5-week dose-titration phase. Changes in electrolytes consistent with TLS that require prompt management can occur as early as 6 to 8 hours following the first dose of VENCLYXTO and at each dose increase. Patients should be assessed for risk and should receive appropriate prophylaxis, monitoring, and management for TLS.

Neutropenia (grade 3 or 4) has been reported and complete blood counts should be monitored throughout the treatment period.

Serious infections including sepsis with fatal outcome have been reported. Monitoring of any signs and symptoms of infection is required. Suspected infections should receive prompt treatment including antimicrobials and dose interruption or reduction as appropriate.
Live vaccines should not be administered during treatment or thereafter until B-cell recovery.

Drug Interactions
CYP3A inhibitors may increase VENCLYXTO plasma concentrations. At initiation and dose-titration phase: Strong CYP3A inhibitors are contraindicated due to increased risk for TLS and moderate CYP3A inhibitors should be avoided. If moderate CYP3A inhibitors must be used, physicians should refer to the SmPC for dose adjustment recommendations. At steady daily dose: moderate or strong CYP3A inhibitors must be used, physicians should refer to the VENCLYXTO summary of product characteristics (SmPC) for dose adjustment recommendations.

Avoid concomitant use of P-gp and BCRP inhibitors at initiation and during the dose titration phase.

CYP3A4 inducers may decrease VENCLYXTO plasma concentrations. Avoid coadministration with strong or moderate CYP3A inducers. These agents may decrease venetoclax plasma concentrations.

Co-administration of bile acid sequestrants with VENCLYXTO is not recommended as this may reduce the absorption of VENCLYXTO.

Adverse Reactions
The most commonly occurring adverse reactions (>=20%) of any grade in patients receiving venetoclax in the combination studies with obinutuzumab or rituximab were neutropenia, diarrhoea, and upper respiratory tract infection. In the monotherapy studies, the most common adverse reactions were neutropenia/neutrophil count decreased, diarrhoea, nausea, anaemia, fatigue, and upper respiratory tract infection.

The most frequently occurring serious adverse reactions (>=2%) in patients receiving venetoclax in combination with obinutuzumab or rituximab were pneumonia, sepsis, febrile neutropenia, and TLS. In the monotherapy studies, the most frequently reported serious adverse reactions (>=2%) were pneumonia and febrile neutropenia.
Discontinuations due to adverse reactions occurred in 16% of patients treated with venetoclax in combination with obinutuzumab or rituximab in the CLL14 and Murano studies respectively. In the monotherapy studies with venetoclax, 11% of patients discontinued due to adverse reactions.

Dosage reductions due to adverse reactions occurred in 21% of patients treated with the combination of venetoclax and obinutuzumab in CLL14 and in 15% of patients treated with the combination of venetoclax and in Murano and in 14% of patients treated with venetoclax in the monotherapy studies. The most common adverse reaction that led to dose interruptions was neutropenia.

Specific Populations
Patients with reduced renal function (CrCl <80 mL/min) may require more intensive prophylaxis and monitoring to reduce the risk of TLS. Safety in patients with severe renal impairment (CrCl <30 mL/min) or on dialysis has not been established, and a recommended dose for these patients has not been determined.

For patients with severe (Child-Pugh C) hepatic impairment, a dose reduction of at least 50% throughout treatment is recommended.

VENCLYXTO may cause embryo-fetal harm when administered to a pregnant woman. Advise nursing women to discontinue breastfeeding during treatment.
This is not a complete summary of all safety information. See VENCLYXTO full summary of product characteristics (SmPC) at View Source Globally, prescribing information varies; refer to the individual country product label for complete information.

About AbbVie in Oncology

At AbbVie, we are committed to transforming standards of care for multiple blood cancers while advancing a dynamic pipeline of investigational therapies across a range of cancer types. Our dedicated and experienced team joins forces with innovative partners to accelerate the delivery of potentially breakthrough medicines. We are evaluating more than 20 investigational medicines in over 300 clinical trials across some of the world’s most widespread and debilitating cancers. As we work to have a remarkable impact on people’s lives, we are committed to exploring solutions to help patients obtain access to our cancer medicines. For more information, please visit View Source