December 7, 2015
Onconova Enrolls First Patient in Phase 3 INSPIRE Trial of Rigosertib
Patient Randomized at MD Anderson Cancer Center; Four U.S. Sites Activate
NEWTOWN, Pa., Dec. 07, 2015 (GLOBE NEWSWIRE) — Onconova Therapeutics, Inc. (NASDAQ:ONTX), a clinical-stage biopharmaceutical company focused on discovering and developing novel products to treat cancer, today announced the enrollment of the first patient in the INSPIRE trial for IV rigosertib as a treatment for higher-risk myelodysplastic syndromes (HR-MDS) after failure of hypomethylating agent (HMA) therapy.
“There is a significant unmet medical need in patients who have failed treatment with an HMA, the only available therapy for HR-MDS,” said Dr. Guillermo Garcia-Manero, lead investigator for the INSPIRE trial and Chief of the Section of Myelodysplastic Syndromes at The University of Texas MD Anderson Cancer Center. “In previous clinical studies, rigosertib demonstrated positive results in HR-MDS patients with very poor prognosis. The INSPIRE trial is designed to assess the effects of IV rigosertib in these HR-MDS patients who have a short life-span and no effective therapies currently available.”
The INSPIRE trial is a global, multi-center, randomized controlled study to assess the efficacy and safety of IV rigosertib in HR-MDS patients under 80 years of age who had progressed on, or failed to respond to, or relapse after previous treatment with HMAs. The trial will enroll approximately 225 patients randomized at a 2:1 ratio into two treatment arms: IV rigosertib plus Best Supportive Care versus Physician’s Choice plus Best Supportive Care. The primary endpoint of INSPIRE is overall survival and an interim analysis is anticipated.
Clinical Trial Applications (CTAs) and/or site initiation activities for INSPIRE have begun in several European countries, Australia and Israel. Onconova’s collaboration partner in Japan and Korea, SymBio Pharmaceuticals, Ltd., will enroll patients in Japan. In addition, Baxalta Incorporated (BXLT), Onconova’s commercialization partner in Europe, is providing financial support for the trial, up to a specified cap.
Rigosertib is a small molecule that inhibits cellular signaling by acting as a Ras mimetic. This is believed to be mediated by direct binding of rigosertib to the Ras-binding domain (RBD) found in many Ras effector proteins, including the Raf kinases and PI3K. The initial therapeutic focus for rigosertib is myelodysplastic syndromes (MDS), a group of bone marrow disorders characterized by ineffective formation of blood cells that often converts into acute myeloid leukemia (AML). Clinical trials for rigosertib are being conducted at leading institutions in the United States, Europe, and the Asia-Pacific region. Rigosertib is protected by issued patents (earliest expiry in 2026) and has been awarded Orphan Designation for MDS in the United States, Europe and Japan.
The INternational Study of Phase III IV RigosErtib, or INSPIRE, is based on guidance received from the U.S. Food and Drug Administration and European Medicines Agency and derives from the findings of the ONTIME Phase 3 trial. INSPIRE is a multi-center, randomized controlled study to assess the efficacy and safety of IV rigosertib in HR-MDS patients under 80 years of age who had progressed on, or failed to respond to, or relapse after previous treatment with HMAs within the first nine months of initiation of HMA treatment. The trial will enroll approximately 225 patients randomized at a 2:1 ratio into two treatment arms: IV rigosertib plus Best Supportive Care versus Physician’s Choice plus Best Supportive Care. The primary endpoint of INSPIRE is overall survival and an interim analysis is anticipated. Full details of the INSPIRE trial, such as inclusion and exclusion criteria, as well as secondary endpoints, can be found on clinicaltrials.gov (NCT02562443).
About Onconova Therapeutics, Inc.
Onconova Therapeutics is a Phase 3 clinical-stage biopharmaceutical company focused on discovering and developing novel products to treat cancer. Onconova’s clinical and pre-clinical stage drug development candidates are derived from its extensive chemical library and are designed to work against specific cellular pathways that are important in cancer cells, while causing minimal damage to normal cells. In addition to rigosertib, the Company’s most advanced product candidate, two other candidates are clinical stage, and several candidates are in pre-clinical stages. For more information, please visit http://www.onconova.com.
Forward Looking Statements
Some of the statements in this release are forward-looking statements within the meaning of Section 27A of the Securities Act of 1933, as amended, Section 21E of the Securities Exchange Act of 1934, as amended, and the Private Securities Litigation Reform Act of 1995, which involve risks and uncertainties. These statements relate to future events or Onconova Therapeutics, Inc.’s future operations, clinical development of Onconova’s product candidates and presentation of data with respect thereto, regulatory approvals, expectations regarding the sufficiency of Onconova’s cash and other resources to fund operating expenses and capital expenditures, Onconova’s anticipated milestones and future expectations and plans and prospects. Although Onconova believes that the expectations reflected in such forward-looking statements are reasonable as of the date made, expectations may prove to have been materially different from the results expressed or implied by such forward-looking statements. Onconova has attempted to identify forward-looking statements by terminology including “believes,” “estimates,” “anticipates,” “expects,” “plans,” “intends,” “may,” “could,” “might,” “will,” “should,” “approximately” or other words that convey uncertainty of future events or outcomes. These statements are only predictions and involve known and unknown risks, uncertainties, and other factors, including Onconova’s need for additional financing and current plans and future needs to scale back operations if adequate financing is not obtained, the success and timing of Onconova’s clinical trials and regulatory approval of protocols, and those discussed under the heading “Risk Factors” in Onconova’s most recent Annual Report on Form 10-K and quarterly reports on Form 10-Q.
Any forward-looking statements contained in this release speak only as of its date. Onconova undertakes no obligation to update any forward-looking statements contained in this release to reflect events or circumstances occurring after its date or to reflect the occurrence of unanticipated events.
CONTACT: Onconova Therapeutics
Benjamin Hoffman, 267-759-3036
Treatment with lenalidomide (Revlimid) improved health-related quality of life (HRQoL) compared with placebo after 24 weeks for low to intermediate risk patients with non-deletion 5q myelodysplastic syndromes (MDS), according to a secondary endpoint analysis of the MDS-005 trial presented at the 2015 International MDS Symposium.
Results from MDS-005, originally presented at the 2014 ASH Annual Meeting, demonstrated that significantly more patients treated with lenalidomide achieved red blood cell transfusion independence (RBC-TI) of at least 56 days compared with placebo (26.9% [43/160 patients] vs 2.5% [2/79 patients]; P <.001), the primary endpoint of the multicenter randomized placebo-controlled study.
Based on the results of MDS-005, Celgene plans to submit a regulatory filing with the FDA in the second half of 2015.
In the current analysis, presented by Valeria Santini, MD, HRQoL was assessed as a secondary endpoint using the European Organization for Research and Treatment of Cancer QLQ-C30 questionnaire at baseline, every 12 weeks thereafter, and at discontinuation.
The questionnaire gathered data on fatigue, dyspnea, physical functioning, emotional functioning and global quality of life from 122 patients who received lenalidomide and 56 who received placebo. All patients included in the study had low or intermediate risk, transfusion dependent MDS that was non-del-5q, and were unresponsive or refractory to erythropoiesis-stimulating agents.
Patients underwent a baseline HRQoL assessment. At week 12, mean changes in HRQoL scores from baseline were not significantly different between treatment arms for the preselected domains. However, by week 24, HRQoL score changes favored lenalidomide versus placebo for all preselected domains. After adjusting for baseline scores, improvement was statistically significant for emotional functioning (P = .047) but not other domains.
“This analysis provides new insights into the clinical results of lenalidomide in non-del-5q patients,” said Santini. “We now have a better understanding of how achievement of transfusion independence impacts quality of life measures.”
RBC-TI of at least 8 weeks was associated with significant improvement (P <.01) across all preselected domains, with improvements also exceeding the prespecified threshold for clinically meaningful change.
In the study, the most common adverse events associated with lenalidomide were related to myelosuppression, including neutropenia (64.4% vs 11.4%) and thrombocytopenia (39.4% vs 7.6%). Grade 3/4 neutropenia occurred in 61.9% and 12.7% in the lenalidomide and placebo groups, respectively, and grade 3/4 thrombocytopenia occurred in 35.6% versus 3.8%.
The FDA granted lenalidomide Subpart H approval in 2005 for patients with transfusion-dependent anemia due to low or intermediate-1 risk MDS associated with a deletion 5q cytogenetic abnormality. The drug is currently only available under a special restricted distribution program. The Risk Evaluation and Mitigation Strategy (REMS) program is designed to avoid embryo-fetal exposure to lenalidomide, as the drug is linked to birth defects or death of unborn babies. Risk impacts both women and men, as lenalidomide can pass into human semen.
In 2006 lenalidomide was approved for use in combination with dexamethasone in patients with multiple myeloma who have received one prior therapy. In February 2015, the FDA expanded this multiple myeloma indication to include use in combination with dexamethasone in newly diagnosed patients. The drug also received approval for the treatment of mantle cell lymphoma in 2013 for use in patients whose disease has relapsed or progressed after two prior therapies, one of which included bortezomib (Velcade).
Santini V, Almeida A, Giagounidis A, et al. The effect of lenalidomide on health-related quality of life (HRQoL) in patients with MDS: results from the MDS-005 trial. Leukemia Research. 2015;39:1s (suppl; abstr 116).
Program to Focus Initially on Non-Hodgkin’s Lymphoma, Myelodysplastic Syndromes and Multiple Myeloma
Studies Planned to Start in Second Half 2015
BOUDRY, Switzerland–(BUSINESS WIRE)– Celgene International II Sàrl, a wholly owned subsidiary of Celgene Corporation (NASDAQ:CELG) today announced that it has entered into a strategic collaboration with MedImmune Limited, a wholly owned subsidiary of AstraZeneca PLC, to develop and commercialize an anti-PD-L1 inhibitor, MEDI4736, for hematologic malignancies. Approximately 1.75 million patients globally suffer from blood cancer and many are in need of new treatment options.
MEDI4736 is a human monoclonal antibody directed against programmed cell death ligand 1 (PD-L1), which helps tumors avoid detection by the immune system. Tumor cells use PD-L1 to turn off the immune system just as it begins to mount a response against them. MEDI4736 helps turn the immune system back on, allowing it to continue its attack on cancer.
“The potential of rationally combining immunotherapies such as MEDI4736 with existing and novel hematology compounds creates new opportunities for patients with blood cancers to live longer, better lives,” said Jacqualyn A. Fouse, Ph.D., President, Global Hematology and Oncology for Celgene. “This strategic collaboration leverages the deep expertise of AstraZeneca/MedImmune in immuno-oncology along with the experience of Celgene in the study and treatment of blood cancers. This collaboration advances Celgene’s already deep, diverse scientific platform to include checkpoint inhibitors, an area of significant promise in hematology.”
Dr. Bahija Jallal, Executive Vice President at MedImmune, said: “We are excited about our strategic collaboration with Celgene, a globally recognized leader in treatments for hematological cancers. This agreement is a great example of how we are accelerating the development of medical innovation in our portfolio in collaboration with other experts, in order to bring life-enhancing new medicines to patients faster. Together with Celgene, we are designing a programme for our anti-PD-L1 that will explore its full clinical potential as a game-changing treatment that could activate the patients’ immune system to fight and change the course of blood cancers in this area of high unmet need.”
Under the terms of the agreement, Celgene will collaborate with AstraZeneca to develop the anti-PD-L1 antibody MEDI4736 in hematology and make an upfront payment of $450 million. Celgene will lead clinical development across all new clinical trials within the collaboration and be responsible for all costs associated with these trials until December 31, 2016, after which it is responsible for 75% of these costs. Celgene will also be responsible for the global commercialization of approved MEDI4736 indications in hematology, and will receive royalty rates starting at 70 percent of worldwide sales from all uses in hematology. Royalty rates will decrease gradually to 50 percent over a period of four years after the first date of commercial sales. This collaboration agreement will become effective upon the expiration or termination of the applicable waiting periods under all applicable antitrust laws.
This strategic collaboration will initially focus on the development of MEDI4736 as combination therapy with Celgene’s pipeline of products and other novel agents for hematologic disorders. Over time, the collaboration could expand to include other assets.
MEDI4736 is not approved in any country for any indication.
MEDI4736 is a human monoclonal antibody directed against programmed cell death ligand 1 (PD-L1), which helps tumors avoid detection by the immune system. MEDI4736 is currently being evaluated in several disease states, including lung, melanoma and head and neck cancer.
About Hematologic Malignancies
The World Health Organization estimates that 1.75 million patients had a hematologic malignancy in 2012. These diseases include lymphoma, leukemia, multiple myeloma and myelodysplastic syndromes. The global incidence of blood cancers continues to rise. By 2030, the incidence of blood cancer overall is predicted to rise by 46 percent, and that of non-Hodgkin’s lymphoma and multiple myeloma by 50 and 60 percent, respectively.
Celgene Corporation, headquartered in Summit, New Jersey, is an integrated global biopharmaceutical company engaged primarily in the discovery, development and commercialization of innovative therapies for the treatment of cancer and inflammatory diseases through gene and protein regulation. For more information, please visit www.celgene.com. Follow us on Twitter @Celgene, and on Pinterest and LinkedIn.
This press release contains forward-looking statements, which are generally statements that are not historical facts. Forward-looking statements can be identified by the words “expects,” “anticipates,” “believes,” “intends,” “estimates,” “plans,” “will,” “outlook” and similar expressions. Forward-looking statements are based on management’s current plans, estimates, assumptions and projections, and speak only as of the date they are made. We undertake no obligation to update any forward-looking statement in light of new information or future events, except as otherwise required by law. Forward-looking statements involve inherent risks and uncertainties, most of which are difficult to predict and are generally beyond our control. Actual results or outcomes may differ materially from those implied by the forward-looking statements as a result of the impact of a number of factors, many of which are discussed in more detail in Celgene Corporation’s Annual Report on Form 10-K and other reports filed with the Securities and Exchange Commission.
All registered trademarks are owned by Celgene Corporation.
We are pleased to announce that VI. International Eurasian Congress of Hematology will be held in the Mardan Palace Hotel in Antalya between 14-18 October 2015.
In 2014, our congress has made progress on becoming one of the world’s leading international conventions with the participation of our colleagues from 34 different countries.
We believe deep in our hearts that with its special concept, the Eurasian Congress of Hematology will fill in a significant gap in our region and serve not only scientifically but also culturally.
Looking forward to meeting with your respected selves in the Mardan Palace Hotel in Antalya between 14-18 October, we would like to extend our kindest regards.
Prof. Dr. Süleyman Dinçer, President of Hematology Specialists Association, Turkey
Prof. Dr. Giuseppe Saglio, Congress President
Astex Pharmaceuticals is conducting a Phase 1-2 clinical trial to determine if ASTX727 is effective for the treatment of patients with IPSS low, intermediate -1, intermediate -2, or high risk MDS (including CMML).
NOW ENROLLING: NCT01566695
QUAZAR Lower-Risk MDS is a study for people with MDS who need blood transfusions due to low red blood cell counts (called anemia) and low platelet counts (called thrombocytopenia).
You may qualify for this study if you*
You may not be eligible for this study if you*
*Additional criteria apply.
For more information about this study, call 646-307-8079 or toll-free at 866-743-9791, e-mail QUAZARMDSstudy@emergingmed.com or visit
NICE has issued final draft guidance recommending lenalidomide (also known as Revlimid and marketed by Celgene) as an option, for treating myelodysplastic syndromes.
Myelodysplastic syndromes (MDS), which are diagnosed in around 2000 people each year in England, are a group of bone marrow disorders characterised by the underproduction of one or more types of blood cells due to dysfunction of the marrow. MDS can lead to life threatening disease including acute myeloid leukaemia (AML), as well as anaemia and increased risk of bleeding and infections.
This appraisal focused on the use of lenalidomide for treating people with a specific type of MDS that is characterised by a chromosomal abnormality called an isolated deletion 5q cytogenetic abnormality. At the moment the main treatment option for people with the particular kind of MDS considered in this appraisal is best supportive care including regular blood transfusions.
Commenting on the final draft guidance, Sir Andrew Dillon, NICE chief executive, said: “The committee heard from clinical experts that lenalidomide is an effective therapy. Celgene – who market lenalidomide – worked with us to provide enough evidence to make it possible for us to recommend it for this group of people.
“Celgene provided a revised analyses and further information on their proposal for a reduction in the cost of the drug to the NHS (patient access scheme).”
Celgene’s patient access scheme involves the NHS paying for lenalidomide treatment for up to 26 monthly cycles. The company will provide the drug free of charge for those people who receive more than 26 monthly cycles.
The draft guidance is now with consultees, who have the opportunity to appeal against it. Until NICE issues final guidance, NHS bodies should make decisions locally on the funding of specific treatments.
Important new survey started by EHA – the European Haematology Association. EHA is interested in finding out if certain medicines are not available in some parts of the country – or in some parts of Europe. Patients, Caregivers, and Healthcare professionals are encouraged to complete this survey. The information from this survey will educate European policy makers to take measures that will help provide effective medicines that are not affordable or are not marketed in specific countries.
Having trouble explaining Myelodysplastic Syndromes in terms your loved ones can understand? This new episode of the health and wellness program HEALTHY BODY, HEALTHY MIND can help explain it for you. If you would like to receive your FREE DVD, please call 609-298-1035 or 800-637-0839 or email email@example.com
Under the aegis of the MDS Foundation, the International Working Group for Prognosis in MDS generated an improved method analyzing MDS patient prognosis more precisely than the initial IPSS.
The European Medicines Agency (EMA) has approved Revlimid® for the treatment of MDS patients with transfusion-dependent anemia associated with the del(5q) chromosomal abnormality.
Under the aegis of the MDS Foundation, the International Working Group for Prognosis in MDS (IWG-PM) analyzed clinical features and outcome data from over 7000 patients and generated a method analyzing MDS patient prognosis more precisely than the initial IPSS. Novel components of this prognostic system include: five rather than three cytogenetic prognostic subgroups with specific and new classifications of a number of less common cytogenetic subsets, splitting the low marrow blast percentage value, and depth of cytopenias. In addition to the major prognostic variables of marrow blasts, cytogenetics and peripheral cytopenias, additive features for survival include patient age, performance status, serum ferritin and LDH. The IPSS-R calculator tool is accessible through the following URLs : http://www.mds-foundation.org/ipss-r-calculator/index.php or http://www.ipss-r.com. An iPhone App for the IPSS-R calculator tool is also accessible through the Apple Store (enter MDS IPSS-R). This IPSS-R should prove beneficial for predicting the clinical outcomes of untreated MDS patients and aiding design and analysis of clinical trials in this disease. Data for both calculator tools are derived from the article: Greenberg P, Tuechler H, Schanz J, et al, Revised International Prognostic Scoring System (IPSS-R) for Myelodysplastic Syndromes. Blood 120: 2454-2465, 2012.
We are proud to be a valued partner of GuideStar, America’s first information service publicizing information about nonprofit organizations. Access the GuideStar link for additional financial information or to learn more about ways to give an annual or planned gift to fund MDS programs and services.
Fast Track for First PrescriptionTM is an optional Celgene Patient Support® service which helps patients on an oral Celgene product receive their first prescription faster.
Additional details about eligibility and enrollment are addressed below.
For more information, or for any questions, call Celgene Patient Support® at 1-800-931-8691.
The specialty pharmacy will contact the patient to:
View the MDS Supplement in the American Journal of Medicine. This supplement is supported by Celgene Corporation. These articles are available on the internet through open access, allowing interested parties to download the entire supplement for free.