On April 23, 2021 Protara Therapeutics, Inc. (Nasdaq: TARA), a clinical stage company developing transformative therapies for the treatment of cancer and rare diseases with significant unmet needs, reported a path forward related to TARA-002 for the treatment of Lymphatic Malformations (LMs), which are rare malformations of the lymphatic vasculature for which there is no U.S. Food and Drug Administration (FDA)-approved treatment (Press release, Protara Therapeutics, APR 23, 2021, View Source [SID1234578413]). Based on feedback from the FDA, the Company intends to complete confirmatory, large-scale, GMP manufacturing comparability in the second half of 2021 and subsequently initiate a clinical study in pediatric LM patients pending alignment with FDA on study design.

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!

"With the benefit of the recent FDA feedback, we will work with the agency to align on a clinical study in pediatric LM patients, which, we believe, combined with the existing dataset for OK-432 (the originator compound for TARA-002), which demonstrated treatment effect and support for strong safety profile in over 500 LM patients, should provide a robust data package for this rare disease," said Jesse Shefferman, Chief Executive Officer of Protara Therapeutics. "We have already begun preparation to initiate a clinical study in LMs and we look forward to continued collaboration with FDA to achieve our goal of delivering the first approved medication for LMs to these patients and their physicians."

TARA-002 is derived from the same cell bank as OK-432, a broad immunopotentiator approved in Japan and Taiwan for the treatment of LMs, where it is currently the standard of care. In 2020, Protara successfully demonstrated initial manufacturing comparability between TARA-002 and the originator compound OK-432, which has been studied in more than 500 patients in one of the largest Phase 2 trials ever conducted in LMs. TARA-002 has been granted Rare Pediatric Disease designation by the FDA for the treatment of LMs.

About Lymphatic Malformations

Lymphatic malformations (LMs) are rare, congenital malformations of lymphatic vessels resulting in the failure of these structures to connect or drain into the venous system. Most LMs are present in the head and neck region and are diagnosed in early childhood during the period of active lymphatic growth, with more than 50% detected at birth and 90% diagnosed before the age of 3 years. The most common morbidities and serious manifestations of the disease include compression of the upper aerodigestive tract, including airway obstruction requiring intubation and possible tracheostomy dependence; intralesional bleeding; impingement on critical structures, including nerves, vessels, lymphatics; recurrent infection, and cosmetic and other functional disabilities.

On April 23, 2021 AbbVie (NYSE: ABBV) reported that the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) adopted a positive opinion for VENCLYXTO (venetoclax) in combination with hypomethylating agents for the treatment of adult patients with newly diagnosed acute myeloid leukemia (AML) who are ineligible for intensive chemotherapy (Press release, AbbVie, APR 23, 2021, View Source [SID1234578398]). The positive CHMP opinion is a scientific recommendation for marketing authorization to the European Commission (EC), which is expected to deliver its final decision on VENCLYXTO combination therapy for use in AML in the first half of 2021.

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 positive CHMP opinion represents the third for an extension of indications for VENCLYXTO. The opinion is based on results from the double-blind, placebo-controlled VIALE-A (M15-656) and the Phase 1b open-label, nonrandomized, multicenter M14-358 trial.

"This positive CHMP opinion for VENCLYXTO in acute myeloid leukemia is a critical step to providing new therapeutic options in the European Union for patients with this devastating disease," said Mohamed Zaki, M.D., Ph.D., vice president and global head of oncology development at AbbVie. "Enabling improved outcomes including potentially prolonging the lives of patients with malignant diseases such as acute myeloid leukemia is part of our mission and an objective we pursue relentlessly every day."

AML is the most common acute leukemia in the world.1 An estimated 160,000 people are currently living with the disease globally. 1 The rate of new cases of acute myeloid leukemia is 4.3 per 100,000 men and women per year.3 It is also among the most difficult blood cancers to treat.2 Despite advances in available therapies and care, the five-year survival rate for patients diagnosed with AML remains approximately 29 percent.3 AML typically worsens quickly, and due to age and comorbidities, not all patients can tolerate intensive chemotherapy.4

"AML is an incredibly aggressive form of cancer, and patients who are diagnosed with this disease are often so ill that they cannot tolerate the intensive chemotherapy that healthcare providers would typically prescribe," said Hartmut Döhner, M.D., Professor of Medicine and Director, Department of Hematology, Oncology, Palliative Care, Rheumatology and Infectious Diseases at University Hospital in Ulm, Germany. "VENCLYXTO combination therapy is a promising advancement for patients and their healthcare providers facing this challenging, lethal form of cancer."

Venetoclax 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.

About the VENCLYXTO AML Clinical Trial Program
AbbVie’s clinical trial program to evaluate VENCLYXTO combination therapy in patients with newly diagnosed acute myeloid leukemia (AML) who were ineligible for intensive chemotherapy included two studies conducted around the world.

VIALE-A (M15-656) Phase 3 Trial
The randomized, double-blind, placebo-controlled VIALE-A (M15-656) trial evaluated the efficacy and safety of VENCLYXTO in combination with azacitidine in patients with newly diagnosed AML who were ineligible for intensive chemotherapy. The study met its primary endpoints of statistically significant improvement of overall survival (OS) and complete remission rate and complete remission with incomplete hematologic recovery (CR + CRi). OS was 14.7 months for the VENCLYXTO plus azacitidine arm versus 9.6 months in the placebo plus azacitidine arm. The study also met secondary endpoints, with the VENCLYXTO plus azacitidine arm resulting in a CR rate of 36.7 percent vs. 17.9 percent in the placebo plus azacitidine arm and a composite complete remission rate (CR + CRi) of 66.4 percent versus 28.3 percent. The safety profile of VENCLYXTO plus azacitidine was consistent with the known side-effect profiles of both agents, and adverse events (AEs) were consistent with expectations for an older AML population; no differences between the two treatment arms with respect to quality-of-life measures were seen. The most frequently reported serious AEs in the VENCLYXTO plus azacitidine arm and placebo plus azacitidine arm were febrile neutropenia (in 30 percent and 10 percent), pneumonia (in 17 percent and 22 percent), sepsis (in 6 percent and 8 percent), and haemorrhage (in 9 percent and 6 percent).5

M14-358 Phase 1b Trial
The non-randomized, open-label M14-358 trial evaluated VENCLYXTO in combination with azacitidine or decitabine in patients with newly diagnosed AML. The trial showed patients treated with VENCLYXTO in combination with azacitidine achieved a CR rate of 44 percent and a CR+CRi rate of 71 percent. The median duration of response for patients treated with VENCLYXTO in combination with azacitidine who achieve a CR or CRi was 21.9 months. Median time to first CR or CRi was 1.2 months (range: 0.7 to 7.7 months). Patients who received VENCLYXTO in combination with decitabine achieved a CR rate of 55 percent and a CR+CRi rate of 74 percent. The median duration of response for patients treated with VENCLYXTO in combination with decitabine who achieved a CR or CRi was 15 months. Median time to first CR or CRi was 1.9 months (range: 0.9 to 5.4 months). The most frequently reported serious AEs in patients receiving VENCLYXTO in combination with azacitidine were febrile neutropenia (31 percent) and pneumonia (26 percent). The most frequently reported serious AEs in patients receiving VENCLYXTO in combination with decitabine were febrile neutropenia (42 percent), pneumonia (29 percent), bacteraemia (16 percent) and sepsis (6 percent).6

About VENCLYXTO (venetoclax)

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

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 and other cancers. Venetoclax is approved in more than 80 countries, including the U.S.

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 CLL when treated with VENCLYXTO.

Patients should be assessed for risk and should receive appropriate prophylaxis, monitoring, and management for TLS. The risk of TLS is a continuum based on multiple factors, including comorbidities. 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.

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, in 15% of patients treated with the combination of venetoclax and rituximab 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 at initiation and during the dose-titration phase. 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 (venetoclax) SmPC at www.ema.europa.eu. 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

On April 23, 2021 Knight Therapeutics Inc. (TSX: GUD) ("Knight") a pan-America (ex-USA) specialty pharmaceutical company, reported that it has entered into a definitive agreement under which Knight will acquire the exclusive rights to manufacture, market and sell Exelon (rivastigmine Patch, Capsules and Solution) in Canada and Latin America (the "Territory"), as well as an exclusive license to use the intellectual property and the Exelon trademark, from Novartis within the Territory (Press release, Knight Therapeutics, APR 23, 2021, View Source;id=202438&p=2193050&I=1206939-c7Z3G6f3m8 [SID1234578415]).

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!

Exelon (rivastigmine) is a prescription product that was first approved in 1997 and is currently registered and sold in approximately 90 countries. Exelon is indicated for the symptomatic treatment of mild to moderately severe dementia in people with Alzheimer’s disease.

At closing, Knight will pay USD $168 million in cash and an additional milestone payment of up to USD $12 million upon the achievement of certain conditions. Exelon had annual revenues for 2020 of approximately 47 Million US dollars for Canada and Latin America.

"We are excited to add Exelon to our portfolio of specialty CNS products and continue to support this well established and important therapy option in an area of such high unmet need as Alzheimer’s", said Samira Sakhia, President and Chief Operating Officer of Knight.

"The acquisition of Exelon leverages Knight’s pan-American (ex-US) platform and further validates our Rest-of-world strategy", said Amal Khouri, Chief Business Officer of Knight. "Exelon will be the first product that we will be selling across our entire territory".

The closing of this transaction is subject to anti-trust clearance in Brazil. In conjunction with closing, Knight will enter into a transition service agreement until transfer of marketing authorization, on a country by country basis during which Knight will receive a net profit transfer. Knight will begin distributing Exelon upon transfer of marketing authorization, on a country by country basis.

Conference Call Notice

Knight will host a conference call and audio webcast to discuss the Exelon acquisition today at 8:30 am ET. Knight cordially invites all interested parties to participate in this call.

Date: Friday, April 23, 2021
Time: 8:30 a.m. ET
Telephone: Toll Free 888-506-0062 or International 973-528-0011
Webcast: www.gud-knight.com or Webcast
This is a listen-only audio webcast. Media Player is required to listen to the broadcast.

Replay: An archived replay will be available for 30 days at https://www.gud-knight.com

On April 23, 2021 Reven Holdings, Inc. ("Reven") reported that it has launched its translational oncology program as a new drug discovery and development initiative that is aimed at changing the therapeutic landscape for difficult-to-treat forms of cancer (Press release, Reven Holdings, APR 23, 2021, View Source [SID1234578416]). The overarching goal of this program is to treat cancer patients more effectively by altering the immediate surroundings of their tumor tissue, also known as the tumor microenvironment (TME). That is because TME is a key contributor to disease progression and metastasis. Several cells in the TME prevent patient’s immune system elements from mounting a strong immune response against cancer cells. Reven Pharmaceuticals is committed to developing new strategies aimed at overcoming the immunosuppressive TME. Specifically, Reven will employ its lead compound RJX for targeting the TGF-beta signaling in cancer patients. Transforming growth factor (TGF)-beta can limit the T-cell infiltration to the TME and inhibits T-cells as well as NK-cells with leads to a markedly diminished anti-tumor immune response within the TME. In addition to the TGF pathway, The SYK-PI3K-AKT signaling pathway is also critical for the survival of cancer cells. Reven Pharmaceuticals will explore new generation inhibitors of this biochemical signaling pathway as a new class of anti-cancer drugs.

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!

Another oncology platform being explored by Reven Pharmaceuticals targets the so-called "Lactate Shuttle" in the TME. Cancer cells specifically use lactate to mediate several environment changes that support tumor growth and stimulate more lactate production. Targeting the "lactate shuttle" by facilitating lactate clearance may eliminate the contribution of lactate to the immunosuppressive TME in cancer patients. It is noteworthy that ingredients of Reven’s anti-inflammatory, investigational drug product RJX have been shown to facilitate lactate clearance.

Dr. Fatih Uckun, the Chief Medical Officer of Reven Pharmaceuticals reviews the proof of concept and clinical impact potential of such innovative strategies aimed at the TME in cancer patients with multiple myeloma in a recent article that was published in the prestigious peer-reviewed high-impact biomedical journal Cancers. The article was published on April 22, 2021:

Uckun, F.M. Overcoming the Immunosuppressive Tumor Microenvironment in Multiple Myeloma. Cancers 2021, 13, 2018. View Source

"Scientific data from multiple studies suggest a tremendous therapeutic potential for the RJX platform and provide the foundation for our optimism regarding the commercialization potential of RJX," said Brian Denomme, Co-founder, President and Chief Operating Officer. "This new article emphasizes our commitment to advancing our pipeline for cancer patients through our translational oncology program," stated Michael Volk, Chief Strategy Officer of Reven. CEO Peter Lange added: "Our goal is to leverage the most recent R&D discoveries about health benefits of TME targeting strategies in our efforts aimed at building a rich product pipeline that includes rationally designed anti-cancer agents that are optimized for specific target indications".

About Rejuveinix (RJX)

RJX is an intravenous (IV) formulation of physiologically compatible compounds that is being developed for more effective treatment of patients with sepsis, including COVID-19 patients with viral sepsis and acute respiratory distress syndrome (ARDS). The clinical safety and tolerability of RJX was confirmed in a recently completed double blind, placebo-controlled Phase 1 dose-escalation study in healthy volunteers (ClinicalTrials.gov Identifier: NCT03680105). It is currently being evaluated as a COVID-19 drug candidate in high risk COVID-19 patients (ClinicalTrials.gov Identifier: NCT NCT04708340; View Source).

About Dr. Uckun

Dr. Uckun is an elected Member of the American Society for Clinical Investigation (ASCI), an honor society for physician-scientists, and an active member of several professional organizations. He received numerous awards for his work on monoclonal antibodies, recombinant cytokines and fusion proteins, radiation sensitizers, kinase inhibitors and targeted therapeutics for difficult-to-treat cancers, including the Stohlman Memorial Award of the Leukemia Society of America, the highest honor given to a Leukemia Society Scholar. He has served as a member of several editorial boards and National Institutes of Health grant review/special emphasis panels.

Dr. Uckun earned his doctoral degrees at the University of Heidelberg, Germany where he also served as an active member of the autologous bone marrow transplant and peripheral stem cell transplant clinical research teams of the Tumor Center. Dr. Uckun completed his residency training in pediatrics, clinical fellowship training in Hematology/Oncology/Blood and Bone Marrow Stem Cell Transplantation, as well as postdoctoral research training in immunology and microbiology at the University of Minnesota. Dr. Uckun has more than thirty years of professional experience in developmental therapeutics with a special emphasis on targeted therapeutics/precision medicines and biopharmaceuticals. He has published more than 500 peer-reviewed papers, authored numerous review articles and book chapters, and is an inventor on numerous patents.

For eleven years, Dr. Uckun worked as a Professor of Bone Marrow Transplantation, Therapeutic Radiology-Radiation Oncology, Pharmacology, and Pediatrics as well as Director of the Biotherapy Institute at the University of Minnesota, where he became the first recipient of the Endowed Hughes Chair in Biotherapy. At the Keck School of Medicine of the University of Southern California, he was a Professor and Head of Translational Research in Leukemia and Lymphoma of the CCBD and a Principal Investigator of the Stem Cell-Regenerative Medicine Initiative for six years. From 2012 to 2015, Dr. Uckun served as chair of the Biotargeting Working Group and a Member of the Coordination and Governance Committee of the National Cancer Institute Alliance for Nanotechnology in Cancer.

Dr. Uckun has held executive positions in multiple biotechnology companies and has extensive regulatory experience. Prior to joining Reven as its Chief Medical Officer and Chief Scientific Officer, Dr. Uckun served as Vice President of Scientific Solutions at Worldwide Clinical Trials, Chief Medical Officer of Oncotelic and Mateon Therapeutics, Head of Immuno-Oncology at Ares Pharmaceuticals, and as Executive Medical Director and Strategy Lead in Global Oncology and Hematology at Syneos Health. Previously, he was Vice President of Research and Clinical Development at Nantkwest, and Chief Scientific Officer of both Jupiter Research Institute and Paradigm Pharmaceuticals. Dr. Uckun is a former Vice Chair of the New Agents Committee as well as a Member of the Leukemia Steering Committee of the Children’s Cancer Study Group, an NCI-funded cooperative clinical trials consortium that coordinated pediatric and adolescent/young adult leukemia trials at 120 institutions in the U.S., Canada, Australia and Europe.

Dr. Uckun has deep knowledge and experience in the treatment of infectious diseases and their complications as well. In particular, he has extensive experience in viral, fungal, and bacterial infections of immunocompromised hosts, septic shock, ARDS, systemic capillary leak syndrome and cytokine release syndrome (CRS). He served as the Principal Investigator of a virus neutralizer project funded by the Defense Advanced Research Projects Agency (DARPA) as part of its unconventional countermeasures program. Dr. Uckun directed several federally funded virology/innate immunity projects and published numerous peer-reviewed papers on RNA viruses and anti-viral agents.

On April 23, 2021 AnaptysBio, Inc. (Nasdaq: ANAB), a clinical-stage biotechnology company developing first-in-class antibody product candidates focused on emerging immune control mechanisms applicable to inflammation and immuno-oncology indications, reported that the European Commission has granted conditional marketing authorization for JEMPERLI (dostarlimab) for use in women with mismatch repair deficient (dMMR)/microsatellite instability-high (MSI-H) recurrent or advanced endometrial cancer who have progressed on or following prior treatment with a platinum containing regimen (Press release, AnaptysBio, APR 23, 2021, View Source [SID1234578400]). The approval makes dostarlimab the first anti-PD-1 therapy available for endometrial cancer in Europe.

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!

JEMPERLI was generated by AnaptysBio using its proprietary somatic hypermutation (SHM) antibody platform and subsequently developed by TESARO, Inc., now a part of GSK, under a collaboration agreement. Eight AnaptysBio-generated therapeutic antibodies have advanced into clinical development to date, and JEMPERLI is the first AnaptysBio-generated antibody to obtain regulatory approval.

"We are delighted that JEMPERLI is the first AnaptysBio-generated antibody to be approved in Europe and look forward to meaningful potential future milestone and royalty revenue from our collaboration with GSK," said Hamza Suria, president and chief executive officer of AnaptysBio. "These revenues will continue to support AnaptysBio’s primary value-creation strategy, which is focused on advancing wholly-owned first-in-class therapeutic antibodies through multiple upcoming clinical catalysts in 2021 and 2022."

JEMPERLI is indicated as a monotherapy for treatment of adult patients with recurrent or advanced dMMR/MSI-H endometrial cancer, who have progressed on, or are being dosed following, prior treatment with a platinum-containing regimen, and is the first indication approved by the European Commission for JEMPERLI. AnaptysBio has earned a $10.0 million milestone payment as a result of this approval. Earlier this month, AnaptysBio earned a $20.0 million milestone payment as a result of approval by the U.S. Food and Drug Administration for JEMPERLI in endometrial cancer. In 2020, AnaptysBio received milestone payments of $10.0 million and $5.0 million for the FDA’s and EMA’s acceptances of the BLA and Marketing Authorisation Application (MAA) filings for JEMPERLI, respectively.

Earlier this year, FDA accepted a subsequent BLA filing for JEMPERLI for the treatment of adult patients with dMMR recurrent or advanced solid tumors who have progressed on or following prior treatment. AnaptysBio recently received a $10.0 million payment from GSK as a result of this milestone. Payments totaling an additional $35 million will be due to AnaptysBio upon the achievement of future regulatory milestones for JEMPERLI in the United States and Europe. Furthermore, $165 million in sales milestones are due to AnaptysBio upon achievement of certain annual JEMPERLI net sales revenues. Royalties due to AnaptysBio for dostarlimab range from 8% to 25% of global net sales, where AnaptysBio will receive 8% of annual global net sales below $1 billion, and 12-25% of net sales above $1 billion. JEMPERLI is also being developed by GSK for the treatment of other tumor types and treatment settings, including currently ongoing phase III trials in recurrent or primary advanced endometrial cancer in combination with chemotherapy standard of care (RUBY) and the phase III FIRST study of platinum-based therapy with dostarlimab and niraparib versus standard of care platinum-based therapy as first-line treatment of stage III or IV non-mucinous epithelial ovarian cancer.

In addition, JEMPERLI is being evaluated as monotherapy and in combination therapy across multiple tumor types and other cancers, including platinum-resistant ovarian cancer, non-small cell lung cancer, multiple myeloma and melanoma.

GSK continues to develop additional antibodies partnered with AnaptysBio, including cobolimab, an AnaptysBio-generated anti-TIM-3 antagonist antibody, and GSK4074386, an anti-LAG-3 antagonist antibody. Under the terms of the collaboration, AnaptysBio is due to receive development and regulatory milestone payments for each of the first two indications for each of these antibodies. AnaptysBio can potentially receive a total of $1.1 billion in aggregate milestone payments under this collaboration. In addition, AnaptysBio will receive royalties ranging from 4% to 8% on global net sales of cobolimab and GSK4074386 and 1% of GSK’s global net sales of ZEJULATM.

Important Information for JEMPERLI in the EU

Indication
JEMPERLI is indicated as monotherapy for the treatment of adult patients with mismatch repair deficient (dMMR)/microsatellite instability-high (MSI-H) recurrent or advanced endometrial cancer (EC) that has progressed on or following prior treatment with a platinum-containing regimen.

Immune-Mediated Adverse Reactions
Immune-related adverse reactions, which may be severe or fatal, can occur in patients treated with antibodies blocking the programmed cell death protein-1 / programmed death-ligand 1 (PD-1/PD-L1) pathway, including JEMPERLI. While immune-related adverse reactions usually occur during treatment with PD-1/PD-L1 blocking antibodies, symptoms can also manifest after discontinuation of treatment. Immune-related adverse reactions may occur in any organ or tissue and may affect more than one body system simultaneously. Important immune-related adverse reactions listed in this section are not inclusive of all possible severe and fatal immune-related reactions.

Early identification and management of immune-related adverse reactions are essential to ensure safe use of PD-1/PD-L1 blocking antibodies. Patients should be monitored for symptoms and signs of immune-related adverse reactions. Clinical chemistries, including liver tests and thyroid function tests, should be evaluated at baseline and periodically during treatment. For suspected immune-related adverse reactions, adequate evaluation including specialty consultation should be ensured.

Based on the severity of the adverse reaction, treatment with JEMPERLI should be withheld or permanently discontinued and corticosteroids (1 to 2 mg/kg/day prednisone or equivalent) or other appropriate therapy administered. Upon improvement to Grade ≤1, corticosteroid taper should be initiated and continued for 1 month or longer. Based on limited data from clinical studies in patients whose immune-related adverse reactions could not be controlled with corticosteroid use, administration of other systemic immunosuppressants can be considered. Hormone replacement therapy for endocrinopathies should be instituted as warranted.

Treatment with JEMPERLI should be permanently discontinued for any Grade 3 immune-related adverse reaction that recurs and for any Grade 4 immune-related adverse reaction toxicity, except for endocrinopathies that are controlled with replacement hormones and unless otherwise specified in the Summary of Product Characteristics (SmPC).

Immune-Related Pneumonitis
Pneumonitis has been reported in patients receiving JEMPERLI. Patients should be monitored for signs and symptoms of pneumonitis. Suspected pneumonitis should be confirmed with radiographic imaging and other causes excluded. Patients should be managed with JEMPERLI treatment modifications and corticosteroids.

Immune-related pneumonitis occurred in 7 (1.4%) of 515 patients, including Grade 2 (1.2%) and Grade 3 (0.2%) pneumonitis. Pneumonitis led to discontinuation of JEMPERLI in 3 (0.6%) patients. Systemic corticosteroids (prednisone ≥ 40 mg per day or equivalent) were required in all 7 patients experiencing pneumonitis. Pneumonitis resolved in 6 (85.7%) patients.

Immune-Related Colitis
JEMPERLI can cause immune-related colitis. Patients should be monitored for signs and symptoms of colitis and managed with treatment modifications, anti-diarrhoeal agents and corticosteroids.

Colitis occurred in 8 (1.6%) patients, including Grade 2 (1.0%) and Grade 3 (0.6%) colitis. Colitis did not lead to discontinuation of JEMPERLI in any patients. Systemic corticosteroids (prednisone ≥ 40 mg per day or equivalent) were required in 2 (28.6%) patients. Colitis resolved in 6 (75.0%) patients experiencing colitis.

Immune-Related Hepatitis
JEMPERLI can cause immune-related hepatitis. Patients should be monitored for changes in liver function periodically as indicated, based on clinical evaluation and managed with JEMPERLI treatment modifications and corticosteroids.

Hepatitis occurred in 1 (0.2%) patient, which was Grade 3. Systemic corticosteroids (prednisone ≥ 40 mg per day or equivalent) were required. Hepatitis did not lead to discontinuation of JEMPERLI and resolved.

Immune-Mediated Endocrinopathies

Hypothyroidism occurred in 37 (7.2%) patients, all of which were Grade 2. Hypothyroidism did not lead to discontinuation of JEMPERLI and resolved in 13 (35.1%) patients.

Hyperthyroidism occurred in 10 (1.9%) patients, including Grade 2 (1.7%) and Grade 3 (0.2%). Hyperthyroidism did not lead to discontinuation of JEMPERLI and resolved in 8 (80%) patients.

Thyroiditis occurred in 2 (0.4%) patients; both were Grade 2. Neither event of thyroiditis resolved; there were no discontinuations of JEMPERLI due to thyroiditis.

Adrenal insufficiency occurred in 7 (1.4%) patients, including Grade 2 (0.8%), and Grade 3 (0.6%). Adrenal insufficiency resulted in discontinuation of JEMPERLI in 1 (0.2%) patient and resolved in 2 (28.6%) patients.

Immune-Mediated Nephritis
Nephritis, including tubulointerstitial nephritis, occurred in 3 (0.6%) patients; all were Grade 2. Systemic corticosteroids (prednisone ≥ 40 mg per day or equivalent) were required in 2 (66.7%) patients experiencing nephritis. Nephritis led to discontinuation of JEMPERLI in 1 (0.2%) patient and resolved in 2 of 3 (66.7%) patients.

Immune-Related Rash
Immune-related rash occurred in 17 (3.3%) patients, including Grade 3 in 6 (1.2%) patients receiving JEMPERLI. The median time to onset of rash was 41 days (range 2 days to 407 days). Systemic corticosteroids (prednisone ≥ 40 mg per day or equivalent) were required in 5 (29%) patients experiencing rash. Rash did not lead to discontinuation of JEMPERLI and resolved in 13 (76.5%) patients.

Immune-Related Arthralgia
Immune-related arthralgia occurred in 21 (4.1%) patients. Grade 3 immune-related arthralgia was reported in 3 (0.6%) patients receiving JEMPERLI. The median time to onset of arthralgia was 87 days (range 1 day to 783 days). Systemic corticosteroids (prednisone ≥ 40 mg per day or equivalent) were required in 2 (9.5%) patients experiencing arthralgia. Arthralgia did not lead to discontinuation of JEMPERLI and resolved in 8 (38%) patients experiencing arthralgia.

Other Immune-Related Adverse Reactions
Given the mechanism of action of JEMPERLI other potential immune-related adverse reactions may occur, including potentially serious events [e.g. myositis, myocarditis, encephalitis, demyelinating neuropathy (including Guillain Barré syndrome), sarcoidosis].

Clinically significant immune-related adverse reactions reported in less than 1% of patients treated with JEMPERLI as monotherapy in clinical studies include autoimmune haemolytic anaemia, pancreatitis, iridocyclitis, uveitis and diabetic ketoacidosis. Patients should be monitored for signs and symptoms of immune-related adverse reactions and managed as described in the SmPC.

Solid organ transplant rejection has been reported in the post-marketing setting in patients treated with PD-1 inhibitors. Treatment with JEMPERLI may increase the risk of rejection in solid organ transplant recipients. The benefit of treatment with JEMPERLI versus the risk of possible organ rejection should be considered in these patients.

Fatal and other serious complications can occur in patients who receive allogeneic haematopoietic stem cell transplantation (HSCT) before or after being treated with a PD-1/PD-L1–blocking antibody. Transplant-related complications include hyperacute graft-versus-host disease (GvHD), acute GvHD, chronic GvHD, hepatic veno-occlusive disease after reduced intensity conditioning, and steroid-requiring febrile syndrome (without an identified infectious cause). These complications may occur despite intervening therapy between PD-1/PD-L1 blockade and allogeneic HSCT. Follow patients closely for evidence of transplant-related complications and intervene promptly. Consider the benefit versus risks of treatment with a PD-1/PD-L1–blocking antibody prior to or after an allogeneic HSCT.

Infusion-Related Reactions
Infusion-related reactions including hypersensitivity occurred in 7 (1.4%) patients, including Grade 2 (1.2%) and Grade 3 (0.2%) infusion-related reactions. All patients recovered from the infusion-related reaction.

Immunogenicity
Anti-drug antibodies (ADA) were tested in 315 patients who received JEMPERLI and the incidence of JEMPERLI treatment-emergent ADAs was 2.5%. Neutralising antibodies were detected in 1.3% of patients. In the patients who developed anti-JEMPERLI antibodies, there was no evidence of altered efficacy or safety of JEMPERLI.

Elderly population
Of the 515 patients treated with JEMPERLI monotherapy, 50.7% were under 65 years, 37.9% were 65-75 years, and 11.5% were 75 years or older. No overall differences in safety were reported between elderly (≥ 65 years) and younger patients (< 65 years).

Pregnancy, Lactation and Fertility
JEMPERLI is not recommended during pregnancy and in women of childbearing potential not using contraception. JEMPERLI should not be used during breast-feeding and breast-feeding should be avoided for at least 4 months after the last dose of JEMPERLI. Fertility studies have not been conducted with JEMPERLI.

COMMON ADVERSE REACTIONS
JEMPERLI is most commonly associated with immune-related adverse reactions. Most of these, including severe reactions, resolved following initiation of appropriate medical therapy or withdrawal of JEMPERLI.

In patients with advanced or recurrent solid tumours (N = 515), the most common adverse reactions (> 10%) were anaemia (25.6%), nausea (25.0%), diarrhoea (22.5%), vomiting (18.4%), arthralgia (13.8%), pruritus (11.5%), rash (11.1%), pyrexia (10.5%) and hypothyroidism (10.1%). JEMPERLI was permanently discontinued due to adverse reactions in 17 (3.3%) patients; most of them were immune-related events. Adverse reactions were serious in 8.7% of patients; most serious adverse reactions were immune-related adverse reactions.