On November 1, 2018 Geron Corporation (Nasdaq: GERN) reported recent company events and reported financial results for the three and nine months ended September 30, 2018 (Press release, Geron, NOV 1, 2018, View Source [SID1234530644]). The Company ended the third quarter of 2018 with $184.8 million in cash and marketable securities and expects to utilize these financial resources to advance the clinical development of imetelstat, the Company’s first-in-class telomerase inhibitor.

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"We are very excited to have 100% ownership of imetelstat, a Phase 3 ready asset with Phase 2 data from both IMerge and IMbark that have been selected for oral presentations at the ASH (Free ASH Whitepaper) meeting in December," said John A. Scarlett, M.D., Geron’s President and Chief Executive Officer. "We are in the process of transitioning imetelstat back to Geron and have the cash to support our key near-term objective of commencing enrollment for the Phase 3 portion of IMerge by mid-year 2019."

Recent Company Events

Geron regained the global rights to develop and commercialize imetelstat upon the termination of a collaboration and license agreement with Janssen Biotech, Inc. (Janssen). The transition of the entire imetelstat program back to Geron is expected to occur over approximately 12 months, through September 2019, with operational support from Janssen. Patients currently enrolled in the ongoing imetelstat clinical trials in myelofibrosis (IMbark) and myelodysplastic syndromes (IMerge) will continue to be supported through the respective trial protocols, including treatment and follow-up. Previously, Geron and Janssen shared both the IMerge and IMbark clinical development costs 50/50. While Geron is now solely accountable for imetelstat development costs, each company will be responsible for their own respective transition costs as the imetelstat program transfers back to Geron.

After sponsorship of the imetelstat Investigational New Drug (IND) application has been transferred from Janssen, Geron plans to initiate the Phase 3 portion of IMerge in lower risk myelodysplastic syndromes (MDS) and is targeting mid-year 2019 for patient screening and enrollment. In addition, Geron intends to discuss the results of the IMbark primary analysis, including the assessment of overall survival as it compares to historical data, with experts in myelofibrosis (MF), as well as regulatory authorities. The Company believes feedback from these discussions will provide important information on the feasibility, scope and design of any potential future clinical trials for imetelstat in Intermediate-2 or High-risk MF patients who have relapsed after or are refractory to prior treatment with a JAK inhibitor.

Third Quarter and Year to Date 2018 Results

For the third quarter of 2018, the Company reported a net loss of $5.6 million, or $0.03 per share, compared to $6.9 million, or $0.04 per share, for the comparable 2017 period. Net loss for the first nine months of 2018 was $19.7 million, or $0.11 per share, compared to $20.5 million, or $0.13 per share, for the comparable 2017 period.

Revenues for the three and nine months ended September 30, 2018 were $165,000 and $691,000, respectively, compared to $163,000 and $874,000 for the comparable 2017 periods. Revenues for the three and nine months ended September 30, 2018 and 2017 included royalty and license fee revenues under various non-imetelstat license agreements. The Company adopted the new revenue recognition accounting standard as of January 1, 2018 using the modified retrospective transition method. Financial results for the three and nine months ended September 30, 2018 are presented under the new accounting standard, but prior period amounts have not been adjusted and continue to be reported under accounting standards used historically. Therefore, there is a lack of comparability to the prior periods presented. As a result, the decrease in revenues for the nine months ended September 30, 2018, compared to the same period in 2017, reflects not only a reduction in the number of active non-imetelstat license agreements, but also a change in the accounting method. However, the Company does not expect the adoption of the new revenue recognition accounting standard to have a material impact to its financial statements on an ongoing basis.

Total operating expenses for the three and nine months ended September 30, 2018 were $7.0 million and $22.2 million, respectively, compared to $7.4 million and $22.3 million for the comparable 2017 periods.

Research and development expenses for the three and nine months ended September 30, 2018 were $2.7 million and $8.4 million, respectively, compared to $2.6 million and $8.5 million for the comparable 2017 periods. The changes in research and development expenses for the three and nine months ended September 30, 2018, compared to the same periods in 2017, primarily reflect the net result of higher personnel related expenses, partially offset by lower costs for our proportionate share of clinical development expenses under the former imetelstat collaboration with Janssen. Geron expects research and development expenses to increase in the future as Geron’s share of imetelstat development costs increases from 50% previously to 100% as of the termination date of the collaboration agreement and as it adds personnel, consultants and a global contract research organization (CRO) to support the further development of imetelstat.

General and administrative expenses for the three and nine months ended September 30, 2018 were $4.3 million and $13.8 million, respectively, compared to $4.8 million and $13.8 million for the comparable 2017 periods. The decrease in general and administrative expenses for the three months ended September 30, 2018, compared to the same period in 2017, primarily reflects the net result of reduced personnel related expenses, including lower stock-based compensation expense, partially offset by higher consulting expenses. Geron expects general and administrative expenses to increase in the future with the elimination of cost-sharing with Janssen as of the termination date of the collaboration agreement for imetelstat patent prosecution expenses and as it adds additional personnel to support the expansion of internal research and development functions.

Interest and other income for the three and nine months ended September 30, 2018 was $1.1 million and $2.2 million, respectively, compared to $363,000 and $1.0 million for the comparable 2017 periods. The increase in interest and other income for the three and nine months ended September 30, 2018, compared to the same periods in 2017, primarily reflects higher yields on the Company’s increased marketable securities portfolio.

Conference Call and Webcast

Geron will host a conference call to discuss third quarter financial results and recent events at 4:30 p.m. ET on Thursday, November 1, 2018.

Participants may access the conference call live via telephone by dialing domestically +1 (877) 303-9139 or internationally +1 (760) 536-5195. The passcode is 7133129. A live, listen-only webcast will also be available on the Company’s website at www.geron.com/investors/events. If you are unable to listen to the live call, an archived webcast will be available on the Company’s website for 30 days.

About Imetelstat

Imetelstat is a novel, first-in-class telomerase inhibitor exclusively owned by Geron and being developed in hematologic myeloid malignancies. Early clinical data suggest imetelstat may have disease-modifying activity through the suppression of malignant progenitor cell clone proliferation, which allows potential recovery of normal hematopoiesis. Ongoing clinical studies of imetelstat include a Phase 2/3 trial called IMerge in lower risk myelodysplastic syndromes (MDS) and a Phase 2 trial called IMbark in Intermediate-2 to High-risk myelofibrosis. Imetelstat received Fast Track designation from the United States Food and Drug Administration for the treatment of patients with transfusion-dependent anemia due to lower risk MDS who are non-del(5q) and refractory or resistant to an erythroid stimulating agent.

On November 1, 2018 Nordic Nanovector ASA (OSE: NANO) reported that an abstract reporting updated results from its LYMRIT 37-01 Phase 1/2 clinical study of Betalutin (177Lu-satetraxetan-lilotomab) in patients with relapsed/refractory indolent non-Hodgkin’s lymphoma (iNHL) has been published ahead of its presentation in a poster at the 60th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting & Exposition (1-4 December 2018 in San Diego, CA, USA) (Press release, Nordic Nanovector, NOV 1, 2018, View Source [SID1234553490]).

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The published dataset (as of 22 June 2018) includes 74 evaluable patients; all patients received Betalutin as a single administration and have six or more months of follow-up. The complete dataset will be presented at ASH (Free ASH Whitepaper).

The conclusions from the updated study results are that Betalutin is well-tolerated and has promising anti-tumour activity in recurrent iNHL, especially in follicular lymphoma (FL) patients. Key results are:

Patients Number of patients (n) Overall Response Rate (ORR) Complete Responses (CR)
All iNHL patients 74 61 % 26 %
FL patients 57 65 % 24 %
3L FL patients (≥2 prior therapies) 37 70 % 27 %
FL patients in Arm 1
(40 mg lilotomab followed by 15 MBq/kg Betalutin) 25 64 % 28 %
FL patients in Arm 4
(100 mg/m2 lilotomab followed by 20 MBq/kg Betalutin) 16 69 % 19 %
The median duration of response (mDoR), when treated with a single administration of Betalutin, was 13.3 months for all patients (20.5 months for those with a CR) based on a median follow-up of 9.1 months (range 4.9-49.5 months). Twenty-six patients (35%) have remained free of disease progression for more than 12 months.

Betalutin therapy was well tolerated with no unexpected safety findings and the safety profile is both predictable and manageable.

The data continue to highlight the encouraging clinical profile of single-agent Betalutin therapy in iNHL patients, particularly in those with FL, the primary NHL population for which Betalutin is being developed.

Two recommended Phase 2 doses were identified from this study and are now being compared in the pivotal, randomised Phase 2b PARADIGME trial in relapsed, anti-CD20 refractory FL patients who have received two or more prior therapies.

Arne Kolstad, lead investigator of LYMRIT 37-01 and senior consultant in medical oncology and radiotherapy, Oslo University Hospital Radiumhospitalet, said: "Patients with relapsed/refractory follicular lymphoma have a need for effective treatment options that improve their quality of life, especially elderly patients. The clinical profile that Betalutin is consistently showing in this patient population is very encouraging."

Lisa Rojkjaer, Chief Medical Officer of Nordic Nanovector, commented: "We are very pleased with the clinical data. The results from Arm 4 further support the decision to compare the 100 mg/m2 lilotomab + 20 MBq/kg Betalutin dosing regimen from Arm 4 with the 40 mg lilotomab + 15 MBq/kg regimen from Arm 1 in the pivotal phase 2b PARADIGME trial. The emerging data on the durability of the responses together with the safety profile of Betalutin and the convenience of a single administration underscore the potential of Betalutin for the treatment of patients with advanced-stage follicular lymphoma."

Poster details

Abstract 2879

Abstract title: LYMRIT 37-01: A phase I/II study of 177Lu-lilotomab satetraxetan (Betalutin) antibody-radionuclide-conjugate (ARC) for the treatment of relapsed non-Hodgkin’s lymphoma (NHL) – Analysis with 6-month follow-up

Authors: A. Kolstad, A et al.

Session Name: 623. Mantle Cell, Follicular, and Other Indolent B-Cell Lymphoma—Clinical Studies: Poster II

Date: Sunday, 2 December 2018

Presentation Time: 6:00 PM – 8:00 PM Pacific time

Location: San Diego Convention Center, Hall GH

The abstract is available at View Source and the poster will be published on the Nordic Nanovector website to coincide with the session.

About ASH (Free ASH Whitepaper)

The ASH (Free ASH Whitepaper) annual meeting is the premier event for scientific exchange in the field of haematology, attracting more than 20,000 attendees from all over the world. Typically, more than 5,000 scientific abstracts are submitted each year, and more than 3,000 abstracts are accepted for oral and poster presentations through an extensive peer review process.

About LYMRIT 37-01

LYMRIT 37-01 is a Phase 1/2 dose-escalation study to determine the safety, pharmacokinetics and preliminary efficacy of a single dose of Betalutin in patients with relapsed iNHL, and to establish a recommended Phase 2 dose for the global, randomised Phase 2b PARADIGME trial.

LYMRIT 37-01 recruited 74 pts [57 follicular (FL), 7 mantle cell (MCL), 9 marginal zone (MZL), 1 small lymphocytic (SLL)] at 13 sites between December 2012 and February 2018. Median age was 68 years (range 38-87; 55% ≥ 65); the median number of prior therapies was 3 (range 1-9); 48 pts (65%) received 2 or more prior therapies.

On November 1, 2018 GT Biopharma, Inc. (OTCQB: GTBP and Euronext Paris GTBP.PA) ("GT Biopharma" or the "Company"), an immuno-oncology biotechnology company focused on innovative treatments based on the company’s proprietary NK-engager and Bispecific Antibody Drug Conjugate platforms, reported that its Investigational New Drug (IND) application to the U.S. Food and Drug Administration (FDA) is now open and it is authorized to initiate a first-in-human Phase 1 study with GTB-3550 (OXS-3550), its first-in-class (TriKE), for the treatment of acute myelogenous leukemia (AML), myelodysplatic syndrome (MDS) and mastocytosis (Press release, GT Biopharma , NOV 1, 2018, View Source [SID1234539521]). The study will be led by Principal Investigator, Sarah A. Cooley, MD, MS, Associate Professor, Division of Hematology, Oncology and Transplantation at Masonic Cancer Center, University of Minnesota.

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"GTB-3550 is a protein immune engager that binds to natural killer (NK) cells and targets them specifically to leukemia cells," said renowned NK cell expert, Jeffrey Miller, MD, Deputy Director, Masonic Cancer Center, University of Minnesota. "Our team has been working on the optimal construct for years and we are excited to see it is ready for clinical testing. In addition, the same TriKE protein will deliver an interleukin-15 stimulus, a growth factor that makes NK cells proliferate and be more active."

"The clinical trials team at the University of Minnesota is excited to commence the Phase 1 trial testing this novel immunotherapeutic agent, GTB-3550," said Dr. Cooley. "Building on over a decade of successful trials using NK cell infusions from related donors to kill tumors, Masonic Cancer Center researchers designed this protein to activate a patient’s own NK cells and, importantly, to direct them to specifically kill CD33+ tumor cells. The pre-clinical data are extraordinarily compelling, and success with GTB-3550 in this study will allow us to develop a broad pipeline of TriKE agents against different tumor targets."

This single center, first-in-human Phase 1 clinical trial of GTB-3550 will enroll up to 60 subjects with CD33-expressing high risk for refractory/relapsed AML, MDS, or advanced systemic mastocytosis. Subjects will receive a single course of GTB-3550 TriKE given as 3 weekly treatment blocks. Each block consists of four consecutive 24-hour continuous infusions of GTB-3550 TriKE followed by a 72-hour break after Block #1 and #2. Disease response will be assessed by bone marrow biopsy performed between Day 21 and Day 42 after the start of the 1st infusion. Follow-up for response and survival continues through 6 months from treatment start. The primary objective from the Phase 1 dose finding portion of the study will be to identify the maximum tolerated dose (MTD) of GTB-3550 TriKE defined as the dose level that most closely corresponds to a dose limiting toxicity rate (DLT) of 20%. The primary objective from the Phase 2 extended portion of the study will be the potential efficacy of GTB-3550 TriKE, measured using rates of complete and partial remission. Subjects experiencing clinical benefit and no unacceptable side effects may be considered for a 2nd course of GTB-3550 TriKE on a compassionate basis.

"The opening of this IND allows us to proceed with our first-in-class TriKE, Phase 1 study and importantly, marks a significant step forward in our clinical development strategy of our potentially revolutionary product candidate," commented Raymond Urbanski, M.D., Ph.D., Chief Executive Officer of GT Biopharma. "We are privileged to be advancing this program with the world’s leading experts in NK cell-based therapy."

GT Biopharma has an exclusive worldwide license agreement with the University of Minnesota to further develop and commercialize cancer therapies using proprietary TriKE technology developed by researchers at the university to target NK cells to cancer.

About Acute Myelogenous Leukemia (AML)

AML is the most common form of adult leukemia with 21,000 new cases expected in 2018 alone, according to the American Cancer Society. AML patients typically receive frontline therapy, most commonly chemotherapy, which includes cytarabine and an anthracycline, a therapy that has not changed in over 40 years. However, there remains a significant unmet need in these therapies with about half of AML patients experiencing relapses or requiring alternative therapies. The Company is developing GTB-3550 to serve as a relatively safe, cost-effective, and easy-to-use therapy for resistant/relapsing AML and could also be combined with chemotherapy as frontline therapy thus targeting the larger patient population.

About Myelodysplastic Syndrome (MDS)

Myelodysplastic syndromes (MDS) are conditions that can occur when the blood-forming cells in the bone marrow become abnormal, leading to low numbers of one or more types of blood cells. There are several different types of MDS, based on how many types of blood cells are affected and other factors, although the most common finding in MDS is a shortage of red blood cells (anemia). The number of people with MDS diagnosed in the U.S. each year is estimated to be ~10,000. MDS is uncommon before age 50 and is most commonly diagnosed in people in their 70s. In about 1 in 3 patients, MDS can progress to AML, a rapidly growing cancer of bone marrow cells.

About Mastocytosis

Mastocytosis is a rare disorder characterized by abnormal accumulations of mast cells in the skin, bone marrow, and internal organs (liver, spleen, gastrointestinal tract and lymph nodes). Cases beginning during adulthood tend to be chronic and involve the bone marrow in addition to the skin, whereas, during childhood, the condition is often marked by skin manifestations with no internal organ involvement and can often resolve during puberty. In most adult patients, mastocytosis tends to be persistent, and may progress into a more advanced category in a minority of patients. Mastocytosis affects both males and females and can begin during childhood or adulthood. In children, 80% of cases appear during the first year of life, and the majority is limited to the skin. Adults who develop mastocytosis more often have systemic forms of the disease. Cutaneous forms of the disease account for less than 5% of adult cases. An estimate of prevalence from a recent population-based study is approximately 1 case per 10,000 people.

About GTB-3550

GTB-3550 (OXS-3550) is the Company’s first Tri-specific Killer Engager (TriKE) product candidate being initially developed for the treatment AML. GTB-3550 is a single-chain, tri-specific scFv recombinant fusion protein conjugate composed of the variable regions of the heavy and light chains of anti-CD16 and anti-CD33 antibodies and a modified form of IL-15. When the NK stimulating cytokine human IL-15 is used as a crosslinker between the two scFvs, it provides a self-sustaining signal that activates NK cells and enhances their ability to kill. We intend to study this anti-CD16-IL-15-anti-CD33 tri-specific killer engager, or TriKE, in CD33 positive leukemias, a marker expressed on tumor cells in AML, myelodysplastic syndrome, or MDS, and other hematopoietic malignancies. CD33 is primarily a myeloid differentiation antigen with endocytic properties broadly expressed on AML blasts and, possibly, some leukemic stem cells. CD33 or Siglec-3 (sialic acid binding Ig-like lectin 3, SIGLEC3, SIGLEC3, gp67, p67) is a transmembrane receptor expressed on cells of myeloid lineage. It is usually considered myeloid-specific, but it can also be found on some lymphoid cells. The anti-CD33 antibody fragment that will be used for these studies was derived from the M195 humanized anti-CD33 scFV and has been used in multiple human clinical studies. It has been exploited as target for therapeutic antibodies for many years. Improved survival seen in many patients when the antibody-drug conjugate gemtuzumab was added to conventional chemotherapy validates this approach. GT Biopharma believes that GTB-3550 could serve as a relatively safe, cost-effective, and easy-to-use therapy for resistant/relapsing AML and could also be combined with chemotherapy as frontline therapy thus targeting the larger patient population.

On November 1, 2018 AbbVie (NYSE: ABBV), a research-based global biopharmaceutical company, reported that the European Commission (EC) has approved the type-II variation application for VENCLYXTO (venetoclax) in combination with rituximab for the treatment of patients with relapsed/refractory chronic lymphocytic leukemia (R/R CLL) who have received at least one prior therapy (Press release, AbbVie, NOV 1, 2018, View Source [SID1234530458]). This approval allows more patients to receive VENCLYXTO in the second-line setting and gives healthcare providers the ability to prescribe this medicine to a broader population of patients with R/R CLL than the previously approved indication for VENCLYXTO as monotherapy in the European Union (EU). The approval is valid in all 28 member states of the EU, as well as Iceland, Liechtenstein and Norway.

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The EC approval is based on results from the MURANO Phase 3 randomized clinical trial, which evaluated the efficacy and safety of VENCLYXTO in combination with rituximab compared to bendamustine in combination with rituximab, an established standard of care chemoimmunotherapy regimen for patients with R/R CLL.1 At the time of the primary analysis, the trial demonstrated a statistically significant improvement in investigator-assessed progression-free survival (PFS; the time on treatment without disease progression or death2) in patients who received VENCLYXTO plus rituximab, resulting in an 83 percent reduction in the risk of disease progression or death (hazard ratio [HR]:0.17; 95% confidence interval [CI]: 0.11-0.25; P<0.0001) and prolonged overall survival (OS) compared to the standard of care chemoimmunotherapy (HR: 0.48; 95% CI: 0.25-0.90; overall survival data are not yet mature).1

In the MURANO Phase 3 clinical trial, undetectable minimal residual disease (uMRD) was a secondary endpoint assessed at the end of combination therapy (nine-month assessment1,3). The majority of patients in the trial who received VENCLYXTO plus rituximab achieved uMRD in the peripheral blood, with 62.4 percent of patients achieving uMRD versus 13.3 percent with bendamustine in combination with rituximab.1 uMRD is an objective measure defined as the presence of less than one CLL cell in 10,000 white blood cells remaining in the blood or bone marrow following treatment.2 Earlier prospective clinical trials have provided evidence that achieving uMRD in CLL patients is associated with improved clinical outcomes.2

"Chronic lymphocytic leukemia can relapse and become refractory to first-line treatment, and there is a need for better therapies to treat these patients who otherwise have limited options," said Prof. John Seymour, MBBS, Ph.D., lead investigator of the MURANO trial and Director of Cancer Medicine at the Peter MacCallum Cancer Centre & Royal Melbourne Hospital in Australia. "The venetoclax plus rituximab combination provides these patients with an alternative treatment option that is superior to a type of chemoimmunotherapy and can achieve deep responses, as shown by MRD negativity rates in the peripheral blood and bone marrow, allowing for a fixed duration of treatment without the need for chemoimmunotherapy."

CLL is a slow-growing form of leukemia, or blood cancer, in which too many immature lymphocytes (a type of white blood cell) are found predominantly in the blood and bone marrow.4 CLL accounts for approximately one third of new leukemia diagnoses.5

In September 2018, AbbVie announced the European Committee for Medicinal Products for Human Use (CHMP) granted a positive opinion for the Marketing Authorization Application for VENCLYXTO plus rituximab for the treatment of patients with R/R CLL.

"The approval of VENCLYXTO in combination with rituximab is an important step forward in providing patients with relapsed/refractory chronic lymphocytic leukemia a strong chance to live longer without their disease progressing," said Michael Severino, M.D., executive vice president, research and development and chief scientific officer, AbbVie. "We look forward to bringing VENCLYXTO to more patients with chronic lymphocytic leukemia, while continuing to further the research and development of therapies with the potential to transform the standards of care in blood cancers."

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.

About the MURANO Trial
A total of 389 patients with R/R CLL who had received at least one prior therapy were enrolled in the international, multicenter, open-label, randomized Phase 3 MURANO trial. The trial was designed to evaluate the efficacy and safety of VENCLYXTO in combination with rituximab (N=194) compared with bendamustine in combination with rituximab (N=195). The median age of patients in the trial was 65 years (range: 22-85).1

The primary efficacy endpoint was investigator (INV)-assessed PFS. Median PFS with VENCLYXTO in combination with rituximab was not reached compared with 17.0 months for bendamustine in combination with rituximab (HR: 0.17; 95% CI: 0.11-0.25; P<0.0001). The median follow-up was 23.8 months (range: 0.0 to 37.4). Additional efficacy endpoints included independent review committee (IRC)-assessed PFS, INV- and IRC-assessed overall response rate (defined as complete response + complete response with incomplete marrow recovery + partial response + nodular partial response), overall survival and rates of uMRD.1

The safety profile of the combination of VENCLYXTO plus rituximab is consistent with the known safety profile of each of the medicines alone. The most common adverse reactions (ARs; ≥20 percent) of any grade for VENCLYXTO in combination with rituximab were neutropenia, diarrhea and upper respiratory tract infection. In the VENCLYXTO in combination with rituximab arm due to any AR, discontinuation occurred in 16 percent of patients, dose reduction in 15 percent, and dose interruption in 71 percent. In the VENCLYXTO in combination with rituximab arm, neutropenia led to dose interruption of VENCLYXTO in 43 percent of patients and discontinuation in 3 percent. The most serious ARs (≥2 percent) for VENCLYXTO in combination with rituximab or VENCLYXTO monotherapy were pneumonia, febrile neutropenia and tumor lysis syndrome.1

About VENCLYXTO (venetoclax)
VENCLEXTA (VENCLYXTO in the EU) is a first-in-class medicine that selectively binds and inhibits the B-cell lymphoma-2 (BCL-2) protein. In some blood cancers and other cancerous tumors, BCL-2 builds up and prevents cancer cells from undergoing their natural death or self-destruction process, which is called apoptosis. VENCLEXTA/VENCLYXTO targets the BCL-2 protein and works to 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 and other cancers.

VENCLEXTA/VENCLYXTO is approved in more than 50 countries, including the U.S. AbbVie and Roche are currently working with regulatory agencies around the world to bring this medicine to additional eligible patients in need.

Important VENCLYXTO (venetoclax) EU Safety Information3

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
Tumor lysis syndrome (TLS), including fatal events, has occurred in patients with previously treated CLL with high tumor 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 events of sepsis with fatal outcome have been reported. Supportive measures including antimicrobials for any signs of infection should be considered.

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: If moderate or strong CYP3A inhibitors must be used, physicians should refer to the 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 study with rituximab were neutropenia, diarrhea, and upper respiratory tract infection. In the monotherapy studies, the most common adverse reactions were neutropenia/neutrophil count decreased, diarrhea, nausea, anemia, fatigue, and upper respiratory tract infection.

The most frequently occurring serious adverse reactions (>=2%) in patients receiving venetoclax in combination with rituximab or as monotherapy were pneumonia, febrile neutropenia and TLS.

Discontinuation due to adverse reactions occurred in 16% of patients receiving venetoclax plus rituximab and 9% receiving venetoclax monotherapy. Dosage adjustments due to adverse reactions occurred in 15% of patients receiving venetoclax plus rituximab and 2% receiving venetoclax monotherapy. Dose interruptions occurred in 71% of patients treated with the combination of venetoclax and rituximab.

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. VENCLYXTO should be administered to patients with severe renal impairment only if the benefit outweighs the risk and patients should be monitored closely for signs of toxicity due to increased risk of TLS.

VENCLYXTO may cause embryo-fetal harm when administered to a pregnant woman. Advise nursing women to discontinue breastfeeding during treatment.

On November 1, 2018 Agios Pharmaceuticals, Inc. (NASDAQ:AGIO), a leader in the field of cellular metabolism to treat cancer and rare genetic diseases, reported that updated data from its isocitrate dehydrogenase (IDH) programs and pyruvate kinase (PK) deficiency program will be presented at the American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting being held December 1 – 4, 2018 in San Diego (Press release, Agios Pharmaceuticals, NOV 1, 2018, View Source [SID1234530488]).

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In total, five abstracts led by Agios describing updated data from the company’s IDH programs and PKD program have been accepted for presentation at ASH (Free ASH Whitepaper).

The accepted abstracts are listed below and are available online on the ASH (Free ASH Whitepaper) conference website: View Source

Oral presentations by Agios:

Title: Ivosidenib (AG-120) Induced Durable Remissions and Transfusion Independence in Patients with IDH1-Mutant Untreated AML: Results from a Phase 1 Dose Escalation and Expansion Study
Date & Time: Monday December 3, 2018 at 7:30 a.m. PST
Oral Abstract Session: 616. Acute Myeloid Leukemia: Novel Therapy, excluding Transplantation: Targeted Therapy
Abstract: 561
Location: Manchester Grand Hyatt San Diego, Seaport Ballroom F
Presenter: Gail J. Roboz, M.D., Weill Cornell Medical College

Title: Ivosidenib or Enasidenib Combined with Induction and Consolidation Chemotherapy in Patients with Newly Diagnosed AML with an IDH1 or IDH2 Mutation is Safe, Effective, and Leads to MRD-Negative Complete Remissions
Date & Time: Monday December 3, 2018 at 7:15 a.m. PST
Oral Abstract Session: 616. Acute Myeloid Leukemia: Novel Therapy, excluding Transplantation: Targeted Therapy
Abstract: 560
Location: Manchester Grand Hyatt San Diego, Seaport Ballroom F
Presenter: Eytan Stein, M.D., Memorial Sloan Kettering Cancer Center

Poster presentations by Agios:

Title: Ivosidenib (AG-120) Induced Durable Remissions and Transfusion Independence in Patients with IDH1-Mutant Relapsed or Refractory Myelodysplastic Syndrome: Results from a Phase 1 Dose Escalation and Expansion Study
Poster Session Date & Time: Saturday December 1, 2018 from 6:15-8:15 p.m. PST
Poster Session: 637. Myelodysplastic Syndromes—Clinical Studies: Poster I
Abstract: 1812
Poster Location: San Diego Convention Center, Hall GH
Author: Courtney Denton DiNardo, M.D., University of Texas MD Anderson Cancer Center

Title: Population Pharmacokinetics of Ivosidenib (AG-120) in Patients with IDH1-Mutant Advanced Hematologic Malignancies
Poster Session Date & Time: Saturday December 1, 2018 from 6:15-8:15 p.m. PST
Poster Session: 613. Acute Myeloid Leukemia: Clinical Studies: Poster I
Abstract: 1394
Poster Location: San Diego Convention Center, Hall GH
Author: Kha Le, Ph.D., Agios Pharmaceuticals

Title: Genotype-Response Correlation in DRIVE PK, a Phase 2 Study of AG-348 in Patients with Pyruvate Kinase Deficiency
Poster Session Date & Time: Monday December 3, 2018 from 6:00-8:00 p.m. PST
Poster Session: 101. Red Cells and Erythropoiesis, Structure and Function, Metabolism, and Survival, Excluding Iron: Poster III
Abstract: 3621
Poster Location: San Diego Convention Center, Hall GH
Author: Charles Kung, Ph.D., Agios Pharmaceuticals