On December 5, 2016 Novartis reported results from the first-ever international survey of patients with myeloproliferative neoplasms (MPNs), specifically myelofibrosis (MF), polycythemia vera (PV) or essential thrombocythemia (ET), which indicate that the majority of patients living with these MPNs experience a reduced quality of life (Press release, Novartis, DEC 5, 2016, View Source [SID1234516970]). The findings also reveal that many patients struggle with emotional distress and experience a negative impact on their ability to work. These data were presented for the first time at the 58th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting in San Diego, CA (abstract #4267, 12/5/16 6:00 PM PDT)[1].

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MPNs are a group of rare and life-threatening blood cancers. People living with an MPN can have a poor quality of life and shortened survival rate[2]. Two of the most debilitating MPNs are MF and PV, as compared to ET[3]. MF and PV are associated with a range of symptoms and complications, including fatigue, night sweats, itchy skin, enlarged spleen and cardiovascular events[2-5]. The international MPN LANDMARK Survey included 699 patients with representation across six countries and four continents and was conducted to gain a better understanding of how MPNs impact a patient’s quality of life, activities of daily living, work productivity and emotional well-being[1].

"Rare blood cancers like MPNs are often not well-recognized, yet these diseases can have a significant impact on even the simplest tasks in a patient’s daily life," said Bruno Strigini, CEO of Novartis Oncology. "We hope the survey results illuminate the awareness of these debilitating blood cancers, emphasizing the need to help optimize patient care."

In the international survey, patients reported that their disease negatively impacted their ability to complete daily activities by 40%. Patients also noted a 35% impairment on their capacity to work. Furthermore, employed patients who missed work over the last seven days due to their disease reported missing an average of 3.1 hours due to their disease and/or symptom burden[1].

"These results help quantify the daily difficulty of living with an MPN, which can help patients explain disease burden to family, friends, colleagues and physicians who may be unfamiliar with these conditions," said Dr. Claire Harrison, Guy’s and St. Thomas’ NHS Foundation Trust, London, United Kingdom. "The survey results also help paint the full picture of the impact of the disease, which will enable physicians to manage the total patient in hopes of increasing quality of life."

Results also demonstrated that more than 75% of patients who experienced symptoms suffered a significant reduction in quality of life due to their symptoms (83% of MF patients, 72% of PV patients, 74% of ET patients); these numbers are consistent with previously-reported literature[2],[6]. The most commonly-reported symptom across disease areas in the last 12 months was fatigue (54% of MF patients, 45% of PV patients, 64% of ET patients), which was also the symptom patients cited they most wanted to resolve. In addition to physical symptoms, approximately one-third of patients in the study felt anxious or worried about their disease, with the greatest impact seen on those with MF and PV (34% of MF patients, 29% of PV patients, 26% of ET patients)[1].

About the International MPN LANDMARK Survey
The international MPN LANDMARK survey is a cross-sectional survey of patients with MPNs (myelofibrosis (MF), polycythemia vera (PV), essential thrombocythemia (ET)) and physicians who treat these conditions across Germany, Italy, United Kingdom, Japan, Canada and Australia. Patients (174 MF, 223 PV, 302 ET) who partook in the survey completed an online questionnaire to measure MPN-related symptoms experienced over the past year and the impact of their condition on their quality of life and ability to work. Additional survey results will be presented next year.

Findings from the international survey complement results from the Incyte-funded MPN LANDMARK survey conducted in the US[1].

About Myeloproliferative Neoplasms (MPNs)
Myeloproliferative neoplasms (MPNs) are a group of related and rare blood cancers in which bone marrow cells responsible for the body’s blood cells develop and function abnormally. Specific MPN conditions include myelofibrosis (MF), polycythemia vera (PV) and essential thrombocythemia (ET)[4],[5],[7].

In patients with MF, their bone marrow can no longer produce enough normal blood cells, causing the spleen to enlarge[8]. MF affects approximately one in every 100,000 people and has similar survival rates as other malignancies, such as breast cancer and colon cancer[2],[9-12].

PV is associated with an overproduction of blood cells that can cause serious cardiovascular complications if left inadequately controlled, such as blood clots, stroke and heart attack[5],[13]. PV affects up to three per 100,000 people globally each year[2],[5].

ET is characterized by an overproduction of platelets and complications which commonly include blood clotting and/or bleeding[7].

On December 5, 2016 NanoString Technologies, Inc. (NASDAQ:NSTG), a provider of life science tools for translational research and molecular diagnostic products, reported advances in precision oncology using the Prosigna Breast Cancer Gene Signature Assay and the PAM50 gene signature, the basis for Prosigna, will be presented at the 2016 CTRC-AACR San Antonio Breast Cancer Symposium (SABCS) (Press release, NanoString Technologies, DEC 5, 2016, View Source [SID1234516969]). In addition, numerous customers will be presenting data generated using NanoString’s nCounter Analysis System, including several involving immuno-oncology.

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"The volume and impact of the clinical research being presented at the SABCS underscores our commitment to improving the lives of breast cancer patients," said Brad Gray, president and chief executive officer of NanoString Technologies. "These studies demonstrate that our Prosigna Assay can improve decision-making in early-stage breast cancer today, and that a modified companion diagnostic version of this assay has future potential in triple negative breast cancer. The studies also show that our nCounter Analysis System is continuing to grow in prominence as an important tool among breast cancer researchers."

NanoString and its collaborators will present three oral presentations and fourteen posters covering Prosigna/PAM50 and other nCounter-based research at SABCS, which is being held December 6-10, 2016.

Following are details for each presentation of data involving Prosigna and the PAM50 gene signature (all times are in Central Standard Time):

Wednesday, December 7, 2016

Abstract: P1-07-10
Poster: Prediction of 10 year distant recurrence (DR) using the Prosigna (PAM50) assay in histological subgroups of a Danish Breast Cancer Cooperative Group (DBCG) cohort of postmenopausal Danish women with hormone receptor-positive (HR+) early breast cancer (EBC) allocated to 5yr of endocrine therapy (ET) alone
Authors: Laenkholm A-V, Jensen M-B, Buckingham W, Schaper C, Knoop A, Eriksen JO, Rasmussen BB, Ferree S, Haffner T, Kiboel T, Ejlertsen B.
Location: Hall 1
Time: 5:00 – 7:00 p.m.

Abstract: P1-09-09
Poster: Efficacy and gene expression results from SOLTI1007 NEOERIBULIN phase II clinical trial in HER2-negative early breast cancer
Authors: Prat A, Ortega V, Villagrasa P, Paré L, Galván P, Oliveira M, Nucíforo P, Lluch A, Morales S, Amillano K, Lopez R, Gonzalez R, Manso L, Martinez J, Llombart A, De la Peňa L, Di Cosimo S, Rubio IT, Harbeck N, Baselga J, Cortés J
Location: Hall 1
Time: 5:00 – 7:00 p.m.
Thursday, December 8, 2016

Abstract: P2-05-04
Poster: Evaluation of intra-tumor heterogeneity, test reproducibility and their impact in breast cancer samples assessed by Prosigna: results from a Decision Impact prospective study and a matched case-control study
Authors: Rouzier R, Bonneau C, Cayre A, Hequet D, Gentien D, Bonhomme A, Mouret-Reynier M-A, Dubot C, Cottu P, Roulot A, Morel P, Salomon A, Callens C, Guinebretiere J-M, Penault-Llorca F
Location: Hall 1
Time: 7:30 – 9:00 a.m.

Abstract: P2-03-03
Poster: Molecular differences between screen-detected and interval breast cancers are largely explained by PAM50 subtypes
Authors: Czene K, Ivansson E, Klevebring D, Tobin NP, Lindström LS, Holm J, Prochazka G, Hilliges C, Palmgren J, Törnberg S, Humphreys K, Hartman J, Frisell J, Rantalainen M, Lindberg J, Hall P, Bergh J, Grönberg H, Li J
Location: Hall 1
Time: 7:30 – 9:00 a.m.

Abstract: P2-05-16
Poster: Establishment of molecular profiling for individual treatment decisions in early breast cancer – clinical impact of PAM50 and PAM50 risk of recurrence score after more than 16 years follow up.
Authors: Naume B, Borgen E, Falk RS, Ohnstad HO, Lien TG, Aaserud M, Sveli MAT, Kyte JA, Kristensen V, Geitvik G, Schlichting E, Wist E, Sørlie T, Russnes H
Location: Hall 1
Time: 7:30 – 9:00 a.m.

Abstract: S3-03
Oral Session: General Session 3
Poster: PAM50 intrinsic subtype as a predictor of pathological complete response following neoadjuvant dual HER2 blockade without chemotherapy in HER2-positive breast cancer: First results of the PAMELA clinical trial
Authors: Prat Aparicio A, Cortes Castan J, Pare L, Galvan P, Bermejo B, Martínez N, Vidal M, Pernas S, Lόpez R, Muñoz M, Nuciforo P, Fasani R, Morales S, Oliveira M, de La Peña L, Peláez A, Llombart A
Location: Hall 3
Time: 10:00 a.m.
Friday, December 9, 2016

Abstract: S6-05
Oral Session: General Session 6: Comprehensive comparison of prognostic signatures for breast cancer in TransATAC
Authors: Sestak I, Buus R, Cuzick J, Dubsky P, Kronenwett R, Ferree S, Sgroi D, Schnabel C, Baehner R, Mallon E, Dowsett M.
Location: Hall 3
Time: 4:15 p.m.
Saturday, December 10, 2016

Abstract: P6-07-01
Poster: Development of a Prosigna (PAM50)-based classifier for the selection of advanced triple negative breast cancer (TNBC) patients for treatment with enzalutamide
Authors: Danaher P, Skewis L, Mashadi-Hossein A, Carey C, Ram N, Gowen-MacDonald J, Harris E, Cesano A, Ferree S, Uppal H, Buckingham W.
Location: Hall 1
Time: 7:30 – 9:00 a.m.
Additional abstracts and posters demonstrate the diverse applications and robust performance of the nCounter Analysis System in immuno-oncology and biomarker validation, including:

Wednesday, December 7, 2016

Abstract: P1-05-22
Poster: The value of RNA-Seq for the detection of clinically actionable targets in breast cancer – A small cohort analysis
Authors: Meissner T, Amallraja A, Mark A, Andrews A, Connolly C, Young B, De P, Williams C, Leyland-Jones B
Location: Hall 1
Time: 5:00 p.m.
Thursday, December 8, 2016

Abstract: P2-04-07
Poster: Immune profiling of post neoadjuvant high metastatic risk (RCB-II/III) residual disease in patients with early triple negative breast cancers
Authors: Irshad S, Cheang M, Gazinka P, Naidoo K, Buus R, Pinder S, Dowsett M, Tutt A
Location: Hall 1
Time: 7:30 – 9:00 a.m.

Abstract: P2-04-19
Poster: Elucidating the tumor immune microenvironment phenotype in early stage untreated BRCA mutated breast cancer patients
Authors: Force J, Abbott S, Broadwater G, Kimmick G, Westbrook K, Hwang S, Kauff N, Stashko I, Weinhold K, Nair S, Hyslop T, Blackwell K, Castellar E, Marcom PK
Location: Hall 1
Time: 7:30 – 9:00 a.m.

Abstract: S4-01
Oral Session: General Session: A novel BRD4 inhibitor enhances endocrine therapy efficacy and circumvents endocrine-resistance in estrogen receptor-positive breast cancer models
Authors: De Angelis C, Nardone A, Cataldo ML, Fu X, Trivedi M, Yi S, Breckenridge D, Chamnsess GC, Vitorino P, Osborne CK, Schiff R
Location: Hall 3
Time: 3:15 – 5:00 p.m.

Abstract: PD5-06
Poster: Prognostic value of molecular tumor infiltrating lymphocyte (mTIL) signatures in HER2-positive breast cancer patients in N9831 and FinHer/FinXX trials
Authors: Chumsri S, Serie DJ, Mashadi-Hossein A, Tenner KS, Lauttia SL, Moreno-Aspitia A, McLaughlin SA, Nassar A, Warren S, Danaher P, Colon-Otero G, Lindman H, Joensuu H, Perez EA, Thompson EA
Location: Stars at Night Ballroom 1&2 – 3rd Level
Time: 5:00 – 7:00 p.m.
Friday, December 9, 2016

Abstract: P4-07-06
Poster: MicroRNAs associated with acquired taxane resistance in a breast cancer cell line model
Authors: Taylor KJ, Chong T, D’Costa A, Yao C, Gourley C, Cameron DA, Bartlett JMS, Spears M
Location: Hall 1
Time: 7:30 – 9:00 a.m.

Abstract: P4-12-09
Poster: The immune response in triple negative breast cancer
Authors: Gillgrass AE, Pond GR, Levine MN, Whelan TJ, Hassell JA, Bane AL
Location: Hall 1
Time: 7:30 – 9:00 a.m.
Saturday, December 10, 2016

Abstract: P6-07-07
Poster: ESR1 amplification and 5′-3′ exon imbalance in metastatic breast cancer
Authors: Oesterreich S, Basudan A, Preideigkeit N, Hartmaier RJ, Bahreini A, Gyanchandani R, Leone JP, Lucas PC, Hamilton RL, Brufsky AM, Lee AV
Location: Hall 1
Time: 7:30 – 9:00 a.m.

Abstract: P6-09-47
Poster: The development of personalized diagnostic tests and therapeutic strategies in breast cancer
Authors: Kutasovic JR, Rozali E, Miranda M, Lakhani SR, Al-Ejeh F
Location: Hall 1
Time: 7:30 – 9:00 a.m.
You can learn more about the Prosigna Breast Cancer Gene Signature at booth #525.

On December 5, 2016 MorphoSys AG (FSE: MOR; Prime Standard Segment, TecDAX; OTC: MPSYY) reported the presentation of updated safety and efficacy data from two ongoing phase 2 clinical studies evaluating MOR208, an Fc-modified investigational antibody targeting CD19, in patients with advanced B-cell malignancies, at the 58th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting in San Diego, California/USA (Press release, MorphoSys, DEC 5, 2016, View Source [SID1234516968]).

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Continued long-lasting responses of more than 26 months reported in patients with relapsed/refractory NHL in a phase 2a trial with MOR208 monotherapy

An oral presentation reported data from a phase 2a study evaluating single-agent MOR208 in 92 patients with various subtypes of relapsed or refractory non-Hodgkin’s lymphoma (NHL) including diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL) and other indolent NHL (iNHL). Results were consistent with prior updates from the study, reflecting in particular a continuation of long-lasting responses of more than 26 months.

"Patients with NHL, who are refractory or show relapse after previous anti-CD20-based therapies, have limited treatment alternatives and usually a very poor prognosis. These updated results illustrate our ongoing efforts to develop MOR208 as a potential new CD19-based antibody therapy for patients suffering from B-cell malignancies, including DLBCL, in phase 2 studies in combination with other cancer drugs," said Dr. Arndt Schottelius, Chief Development Officer of MorphoSys AG.

At the last cutoff date, June 3, 2016, three patients with DLBCL and six with iNHL were in remission and on study treatment, with the longest responses in both subgroups ongoing for more than 26 months. Of these nine patients, seven showed complete responses and 2 experienced partial responses. The median duration of response was 20.1 months for DLBCL and not yet reached for iNHL. The overall response rate (ORR), based on complete responses (CR) and partial responses (PR), was 36% in the DLBCL subgroup and 33% in iNHL patients (both based on evaluable patients). Based on all patients with DLBCL and iNHL in the study, the ORR was 26% and 29%, respectively. The progression free survival (PFS) rate at 12 months was 39% in both subgroups. In addition to the patients with an objective response (PR or CR), the majority of patients with stable disease (SD) (5/6 DLBCL and 14/17 iNHL) had a reduction in target lesion size (central assessment).

PFS was similar in patients with rituximab non-refractory versus rituximab refractory tumors. Fifty-two patients (57%) in the study were classified as having rituximab refractory disease. Of those, five of 24 patients (21%) with DLBCL and five of 22 patients (23%) with iNHL responded to MOR208. Of the 10 responders with rituximab refractory disease, six had a response duration longer than 10 months, two of which lasted for more than 26 months.

The most common adverse events were infusion-related reactions (IRRs) occurring in 12% of the patients (11% of grade 1 or 2, 1% of grade 4) and neutropenia occurring in 12% of patients (3% of grade 1 or 2, 9% of grade 3 or higher). No treatment-related deaths were reported.

Number and title of the presentation
Abstract #623
Jurczak et al: Single-Agent MOR208 in Relapsed or Refractory (R-R) Non-Hodgkin’s Lymphoma (NHL): Results from Diffuse Large B-Cell Lymphoma (DLBCL) and Indolent NHL Subgroups of a Phase IIa Study

Combination of MOR208 with lenalidomide and ibrutinib in CLL from phase 2 investigator-initiated trial

A second presentation is a poster from investigators at The Ohio State University, who reported on an investigator-initiated trial (IIT) evaluating MOR208 in combination with lenalidomide in three cohorts of patients with chronic lymphatic leukemia (CLL): previously untreated CLL patients, relapsed/refractory CLL patients; and patients with Richter’s Transformation.

The trial also included a 4th cohort of ibrutinib-treated CLL patients with identified resistance mutations to ibrutinib in the tumors (molecular relapse) but no confirmed clinical relapse where MOR208 was added to ibrutinib therapy. Recent data have generally shown poor clinical outcomes in patients who relapse after a therapy with the BTK inhibitor ibrutinib and whose leukemia cells carry a mutation in the BTK gene prior to relapse.

According to the data presented, 34 patients have been enrolled in the study so far, 27 receiving MOR208 in combination with lenalidomide (11 of which in the previously untreated cohort, 11 in the relapsed/refractory cohort, 5 in the Richter’s Transformation cohort) and 7 receiving MOR208 plus ibrutinib, with patient accrual still ongoing.

Most frequent hematological adverse event over all cohorts were thrombocytopenia in 47% of patients (9% grade 3 or higher) and neutropenia in 35% (21% grade 3 or higher). There were no unexpected serious adverse events reported.

According to the abstract, in the group of CLL patients with ibrutinib-resistant cells receiving MOR208 in addition to ibrutinib, four out of seven patients have been on study for at least 3 cycles of 28 days each already, and no patient had developed progressive disease at the time of abstract data cut-off. Preliminary activity has been seen in all cohorts, including ibrutinib-resistant CLL patients.

"There is a high unmet medical need for CLL patients, especially those showing resistance to ibrutinib therapy," said Dr. Jennifer Woyach, Assistant Professor of Internal Medicine at Ohio State University. "Therefore we added an additional cohort to our ongoing CLL study to evaluate MOR208 in combination with ibrutinib in order to investigate whether MOR208 could be a promising combination partner in this setting. We are looking forward to the continuation of the trial and to present further results going forward."

Number and title of the presentation
Abstract #4386
Woyach et al: Updated Results from a Phase II Study of the Fc Engineered CD19 Antibody MOR208 in Combination with Lenalidomide for Patients with Chronic Lymphocytic Leukemia (CLL) and Richter’s Transformation or Ibrutinib for Patients with Ibrutinib-Resistant Clones

MorphoSys held an Investor & Analyst Event at the 2016 ASH (Free ASH Whitepaper) Annual Meeting on December 5, 2016, at 8:00pm PST (December 6, 2016: 4:00am GMT, 5:00am CET). Two clinical investigators presented clinical data for MorphoSys’s investigational agents MOR208 and MOR202.
A replay and the presentation will be made available at View Source
Webcast: View Source

On December 5, 2016 Actinium Pharmaceuticals, Inc. (NYSE MKT:ATNM) ("Actinium" or "the Company"), a biopharmaceutical company developing innovative targeted therapies for cancers lacking effective treatment options, reported that results from its Phase 1 trial of Actimab-A were presented at the 58th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting (ASH) (Free ASH Whitepaper) that is currently ongoing in San Diego, CA (Press release, Actinium Pharmaceuticals, DEC 5, 2016, View Source [SID1234516965]). Data from the previously conducted Phase 1 study pertaining to safety, efficacy and PB burden were highlighted during the poster session. Actimab-A is currently being studied in a 53-patient Phase 2 clinical trial as a monotherapy for patients newly diagnosed with Acute Myeloid Leukemia (AML) age 60 and above who are ineligible for currently used induction therapies. The Phase 2 trial is studying Actimab-A as a monotherapy administered via two fifteen minute intravenous injections of 2.0 μCi/kg/fraction of Actimab-A given a week apart. PB burden below 200 blasts/µL will serve as an inclusion criteria and patients above this threshold will be administered hydroxyurea to reduce their peripheral blasts counts prior to Actimab-A administration. Results from the Phase 1 trial showed that patients with PB burden below 200 blasts/µL who received a dose of 2.0 μCi/kg/fraction of Actimab-A saw a 50% response rate.

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Actinium’s PB burden hypothesis states that patients below the key threshold level of 200 blasts/µL have an increased response rate to Actimab-A while patients above the key threshold are unlikely to respond. An analysis of 2 clinical trials with Actimab-A totaling 38 patients, of which 36 were evaluable, showed that 42% (8 of 19) of patients with blasts counts below 200/µL responded to Actimab-A while no patients with blast counts above 200/µL responded to Actimab-A. The Phase 1 trial was a dose escalation study using a 3+3 design. Dose escalation proceeded if dose-limiting toxicities (DLT) were seen in less than 33% of patients. Maximum tolerable dose (MTD) was not reached in the Phase 1 trial.

Dr. Joseph Jurcic, Director of Hematologic Malignancies and Professor of Medicine at Columbia University Medical Center and Principal Investigator of the study said, "Older patients with AML, particularly those that have progressed from MDS, are difficult to treat and have very few treatment options since many have already received lower-intensity therapy with hypomethylating agents. The results from this Phase 1 trial were encouraging in regards to both the safety and efficacy of Actimab-A. We are particularly excited to have identified that patients with peripheral blasts below 200/µL have higher response rates to Actimab-A and that we can reduce blast counts in patients above that level using hydroxyurea. Actimab-A has shown promise in older AML patients, including those previously treated for MDS–a population excluded from trials with most novel agents, including ongoing studies with other CD33-directed therapies. We look forward to continuing to study Actimab-A in the ongoing Phase 2 trial and potentially meeting this critical need."

Of the 18 patients in the Phase 1 trial, 28% (5 of 18) had objective responses (2 CR, 1CRp and 2 CRi). Amongst patients with objective responses, median response duration was 9.1 months (range, 4.1-16.9 months). At the 3 highest dose levels in the Phase 1 trial (1.0 μCi/kg/fraction – 2.0 μCi/kg/fraction) objective responses were seen in 33% of patients (5 of 15). Mean bone marrow blast reduction amongst evaluable patients was 66% with 57% of patients having bone marrow blast reduction of 50% or greater and 79% of patients (11 of 14) had bone marrow blast reductions after Cycle 1 of therapy. The Phase 1 trial enrolled patients newly diagnosed with AML who are age 60 and above who were administered Actimab-A in combination with low-dose Cytarabine. Median patient age was 77 with 67% of patients having prior myelodysplastic syndrome (MDS) of which, 83% received prior therapy consisting of either hypomethylating agents (HMAs) or a hematopoietic stem cell transplant (HSCT).

A formal interim analysis will occur after 31 patients receive Actimab-A, which the Company expects to occur in mid-2017. The Company anticipates the Phase 2 trial to be complete by the end of 2017.

"Actimab-A, given its benign toxicity profile combined with potent efficacy as evidenced by the results presented today along with its ease of administration via 2 injections, represents an exciting therapy for elderly patients with AML," said Sandesh Seth, Executive Chairman of Actinium. "Due to our peripheral blast burden hypothesis and optimized Phase 2 protocol we have great excitement for the current Phase 2 clinical trial and future development pathways for Actimab-A."

About Actimab-A

Actimab-A, Actinium’s most advanced alpha particle immunotherapy (APIT) product candidate, is currently in a 53-patient, multicenter Phase 2 trial for patients newly diagnosed with AML age 60 and above. Actimab-A is being developed as a first-line therapy and is a monotherapy that is administered via two 15-minute injections that are given 7 days apart. Actimab-A targets CD33, a protein abundantly expressed on the surface of AML cells via the monoclonal antibody, HuM195, which carries the potent cytotoxic radioisotope actinium-225 to the AML cancer calls. Actinium-225 gives off high-energy alpha particles as it decays, which kill cancer cells and as actinium-225 decays it produces a series of daughter atoms, each of which gives off its own alpha particle, increasing the chances that the cancer cell will be destroyed. Actimab-A is a second-generation therapy from the Company’s HuM195-Alpha program, which was developed at Memorial Sloan Kettering Cancer Center and has now been studied in almost 90 patients in four clinical trials. Actimab-A has been granted Orphan Drug Designation for newly diagnosed AML age 60 and above

On December 5, 2016 Sunesis Pharmaceuticals, Inc. (Nasdaq:SNSS) reported the presentation of updated results from the VALOR trial examining overall survival in patients age 60 years and older with relapsed/refractory AML (Press release, Sunesis, DEC 5, 2016, View Source;p=RssLanding&cat=news&id=2227712 [SID1234516964]). The results are being presented today at 3:15 PM PT in an oral session titled "Acute Myeloid Leukemia: Novel Therapy, excluding Transplantation: Clinical trials of Novel Drugs and Combinations in AML" taking place from 2:45 PM – 5:45 PM PT at the 58th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting in San Diego, California. The presentation (abstract 903, Marriott Marquis San Diego Marina, Ballroom AB), titled "Durable Overall Survival Benefit in Patients ≥ 60 Years with Relapsed or Refractory AML Treated with Vosaroxin/Cytarabine Vs Placebo/Cytarabine: Updated Results from the Valor Trial," is available at www.sunesis.com.

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"Clinical outcomes among patients with relapsed/refractory AML remain abysmal, particularly among older patients," said Farhad Ravandi, M.D., Professor of Medicine, Department of Leukemia, University of Texas MD Anderson Cancer Center, and a principal investigator of the VALOR study. "Results from the updated survival data from VALOR and the post-hoc analyses presented today, show compelling durable survival outcomes among older patients, and support the use of vosaroxin, in combination with cytarabine, as an important treatment option for this group of AML patients desperately in need of new therapies."

VALOR is a randomized, double-blind, placebo-controlled Phase 3 trial that enrolled 711 adult patients with first relapsed or refractory AML at 124 sites in 15 countries. Patients were stratified for age, geographic region and disease status and randomized one to one to receive either vosaroxin and cytarabine or placebo and cytarabine. At the time of the primary analysis in October 2014, the overall survival (OS) was significantly improved with vosaroxin/cytarabine versus placebo/cytarabine in patients age 60 years and older (7.1 months vs 5.0 months, HR=0.75, p=0.0030), with a complete remission (CR) rate of (31.9% vs 13.8%, p < 0.0001).

The new data presented today from the VALOR trial include an updated survival analysis in the 451 patient subset age 60 and older, sensitivity analyses of OS in patients age 60 and older, and analyses examining the differences in treatment effect by age. The results demonstrate that, after a median of 39.9 months of follow-up, OS for patients age 60 years and older remains significantly improved for the vosaroxin/cytarabine arm compared to the placebo/cytarabine arm (figure 1), with survival curves remaining separated through 48 months.

Figure 1.

A graph accompanying this announcement is available at View Source

Treatment Arm Patients, n Events, n (%) Censored, n (%) Median OS (95% CI) P value (2-sided)
Pla+Cyt 225 212 (94.2%) 13 (5.8%) 5.0 (3.8-6.4) 0.0017
Vos+Cyt 226 199 (88.1%) 27 (11.9%) 7.1 (5.8-8.1)
Of note, twice as many patients were alive on the vosaroxin-containing arm at both the 24 and 36 months’ time points highlighting the durability of benefit observed in this patient group.

An OS benefit with the addition of vosaroxin was observed consistently across smaller subgroups above 60 years (figure 2). Smaller age groups below 60 years did not demonstrate a similar OS benefit.

Figure 2.

Median OS, months
Patent Age Vosaroxin/Cytarabine Placebo/Cytarabine Hazard Ratio (95% CI)
60-64 years (n = 124) 8.1 5.2 0.72 (0.49-1.06)
65-74 years (n = 293) 7.0 5.0 0.76 (0.60-0.97)
75-84 years (n = 34) 5.5 3.3 0.72 (0.36-1.45)
Sunesis also performed a multivariate survival analysis adjusting for baseline prognostic factors. In this analysis, the HR for OS in the ITT population was 0.80 (p=0.0114) and for patients age 60 and older the OS HR was 0.68 (p=0.0004).

"All of these data and analyses further underscore the consistency, durability and robustness of the survival benefit for patients age 60 years and older who received vosaroxin in the VALOR study," said Daniel Swisher, President and Chief Executive Officer of Sunesis. "As we work toward a European regulatory decision for vosaroxin in this patient population, we remain committed to making vosaroxin available as a new treatment option for underserved patients with relapsed refractory AML. As our regulatory efforts progress, we also continue to advance active dialogues with potential pharma collaborators toward the goal of supporting a European market launch in 2017."

About QINPREZO (vosaroxin)

QINPREZO (vosaroxin) is an anti-cancer quinolone derivative (AQD), a class of compounds that has not been used previously for the treatment of cancer. Preclinical data demonstrate that vosaroxin both intercalates DNA and inhibits topoisomerase II, resulting in replication-dependent, site-selective DNA damage, G2 arrest and apoptosis. Both the U.S. Food and Drug Administration (FDA) and European Commission have granted orphan drug designation to vosaroxin for the treatment of AML. Vosaroxin is an investigational drug that has not been approved for use in any jurisdiction.

Vosaroxin’s Marketing Authorization Application for relapsed refractory AML is currently under review by the European Medicines Agency, and a regulatory decision regarding approval is expected in 2017.

The trademark name QINPREZO is conditionally accepted by the FDA and the EMA as the proprietary name for the vosaroxin drug product candidate.