On March 21, 2017 Actinium Pharmaceuticals, Inc. (NYSE MKT:ATNM) ("Actinium" or "the Company"), a biopharmaceutical Company developing innovative targeted payload immunotherapeutics for the treatment of advanced cancers, announced today that the Company has received positive Scientific Advice from the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) related to the EU approval pathway for Iomab-B (Press release, Actinium Pharmaceuticals, MAR 21, 2017, View Source [SID1234518226]). In its correspondence to Actinium, the EMA commented that the trial design, primary endpoint and planned statistical analysis of the U.S. pivotal Phase 3 SIERRA (Study of Iomab-B in Relapsed or Refractory AML) trial are acceptable and can serve as the basis for submission of a Marketing Authorization Application. In addition, the EMA commented that it does not anticipate the need for further standalone preclinical toxicology or safety studies. The EMA requested supporting data and information that is already being collected as part of the U.S. pivotal Phase 3 SIERRA trial. The SIERRA trial is a 150 patient, randomized controlled study of Iomab-B that is currently enrolling patients in the U.S. Upon approval, Iomab-B is intended to be an induction and conditioning agent prior to a bone marrow transplant (BMT), often referred to as a hematopoietic stem cell transplant (HSCT) with an initial indication in patients with relapsed or refractory acute myeloid leukemia (AML) who are age 55 and above. Schedule your 30 min Free 1stOncology Demo! "We thank the EMA for their assistance throughout the Scientific Advice process and for this helpful feedback." said Sandesh Seth, Executive Chairman of Actinium. "We are excited that the EMA finds the design, endpoints and statistical analysis of the Iomab-B SIERRA trial acceptable. Their opinion is an extremely favorable outcome as this will potentially reduce the time and cost to gain marketing authorization in the EU, which is a larger addressable market than the U.S. in terms of number of patients and transplant procedures. With orphan designation for Iomab-B in the EU and now with this positive Scientific Advice, a clear regulatory pathway, we are well positioned to maximize the value of Iomab-B by working strategically to make this potentially curative therapy available to patients in the EU in addition to our efforts in the U.S."
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The EMA provides scientific advice to companies regarding the appropriate studies for the development of a medicine. The goal of scientific advice is to facilitate the development and availability of high-quality, effective and acceptably safe medicines, for the benefits of patients. Scientific Advice helps companies make sure they perform the appropriate tests and studies, so that no major objections regarding the design of tests are likely to be raised during the evaluation of a marketing authorization application. The EMA created this program to increase the probability of positive outcomes and to reduce the risk of objections during the evaluation of a market-authorization application. Following the EMA’s advice increases the probability of a positive outcome.
About Iomab-B
Iomab-B, Actinium’s lead product candidate, is currently being studied in the pivotal Phase 3 SIERRA (Study of Iomab-B in Relapsed or Refractory AML) trial, a 150-patient, randomized controlled clinical trial in patients with relapsed or refractory acute myeloid leukemia (AML) who are age 55 and above. The SIERRA trial is being conducted at preeminent transplant centers in the U.S. with the primary endpoint of durable Complete Remission (dCR) at six months and a secondary endpoint of overall survival at one year. Upon approval, Iomab-B is intended to prepare and condition patients for a bone marrow transplant, also referred to as a hematopoietic stem cell transplant in a potentially safer and more efficacious manner than intensive chemotherapy conditioning that is standard of care in bone marrow transplant conditioning currently. A bone marrow transplant is often considered the only potential cure for patients with certain blood-borne cancers and blood disorders. Iomab-B targets cells that express CD45, a pan-leukocytic antigen widely expressed on white blood cells with the monoclonal antibody, BC8, labeled with the radioisotope, iodine-131. By carrying iodine-131 directly to the bone marrow in a targeted manner, Actinium believes Iomab-B will avoid the side effects of radiation on most healthy tissues while effectively killing the patient’s cancer and marrow cells. In a Phase 2 clinical study in 68 patients with advanced AML or high-risk myelodysplastic syndrome (MDS) age 50 and older, Iomab-B produced complete remissions in 100% of patients and these patients experienced transplant engraftment at day 28. The overall survival rate of the 36 relapsed or refractory AML patients in the proof of concept study was 30% at one year and approximately 20% at two years. Iomab-B was developed at the Fred Hutchinson Cancer Research Center where it has been studied in several Phase 1 and Phase 2 trials in almost 300 patients in a number of blood cancer indications, including acute myeloid leukemia (AML), chronic myeloid leukemia (CML), acute lymphoblastic leukemia (ALL), chronic lymphocytic leukemia (CLL), Hodgkin’s disease (HD), Non-Hodgkin lymphomas (NHL) and multiple myeloma (MM) and is currently being studied in several ongoing physician trials. Iomab-B has been granted Orphan Drug Designation for relapsed or refractory AML in patients 55 and above by the U.S. Food and Drug Administration and the European Medicines Agency.
Month: March 2017
Heat Biologics Reports Positive Interim Phase 2 Lung Cancer Results in Patients Treated with HS-110 in Combination with a Checkpoint Inhibitor
On March 21, 2017 Heat Biologics, Inc. ("Heat") (Nasdaq:HTBX), a leader in the development of immunotherapies designed to activate a patient’s immune system against cancer, reported the latest results of its ongoing Phase 2 clinical trial of HS-110 in combination with Bristol-Myers Squibb’s anti-PD-1 checkpoint inhibitor, nivolumab (Opdivo), for the treatment of non-small cell lung cancer (NSCLC) (Press release, Heat Biologics, MAR 21, 2017, View Source [SID1234518225]). Fifteen patients have completed the HS-110/nivolumab combination treatment to-date and 12 of these 15 patients were evaluable for ELISPOT analysis. Researchers reported a strong correlation between T cell activation, tumor reductions and increased overall survival in these 12 patients. These data reinforce preliminary results seen in the first eight patients as reported last December at the International Association for the Study of Lung Cancer Annual Meeting. Schedule your 30 min Free 1stOncology Demo! Key findings:
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Immune responses to HS-110 were observed in all 5 patients that exhibited tumor reductions.
No tumor reductions were observed in patients that did not mount an immune response to HS-110.
The timing of immune responses to HS-110 corresponded to the timing of observed clinical responses, and those responses appear to be sustained.
To-date, 5 patients have been enrolled in the low tumor infiltrating lymphocytes (TIL) cohort (patients with "cold" tumors). Three of these 5 patients (60%) have experienced significant tumor reduction, which is higher than the 10% response rate of low TIL patients reported for existing data on nivolumab alone.1
Researchers reported continued indications that patients are mounting a vaccine-mediated immune response to the vaccine lysate, as well as to peptides derived from cancer-specific antigens in their peripheral blood cells via ELISPOT analysis. ELISPOT analysis is the most widely used method for monitoring cellular immune responses in humans. This suggests that the HS-110 vaccine is making a measurable contribution to the desired cancer-specific immune response.
Of the 15 patients who have completed the HS-110/nivolumab combination treatment to-date, 12 were evaluable for ELISPOT analysis. Six of the 12 evaluable patients met the criteria for a positive ELISPOT response to vaccine lysate, and 5 of these 6 patients experienced tumor reductions and increased overall survival. All 5 patients who exhibited a clinical response also saw an immune response to HS-110. Of the 6 patients who did not respond by ELISPOT analysis, 5 patients saw tumor progression and 1 patient discontinued treatment due to a non-serious adverse event.
These data suggest that the 5 tumor reductions seen thus far in the 15 evaluated patients are the result of synergistic activity between HS-110 and anti-PD-1 therapy. Researchers also reported that the safety profile continues to be favorable in the HS-110/nivolumab combination, with no evidence of additional toxicities seen as compared to existing data on nivolumab alone.
"Checkpoint inhibitors, such as nivolumab, are currently effective in treating approximately 10% of lung cancer patients with low TIL and about 20% of patients overall in the 2nd line setting," said Jeff Hutchins, Ph.D., Heat’s Chief Scientific Officer and Senior Vice President of Preclinical Development. "Our results appear to further validate the expected mechanism of action of our approach in combination with checkpoint inhibitors, with a continuing trend towards early and sustained T cell activation in the peripheral blood cells. All patients who mounted a sustained immune response to HS-110 exhibited substantial tumor reductions. We do not see any tumor reduction in patients who did not mount a response to the vaccine. Furthermore, if ELISPOT assay results continue to correlate with clinical results, the combination of HS-110 and nivolumab may become an attractive therapeutic approach for the approximately 80% of patients that do not respond well to nivolumab alone, particularly with the positive safety profile of this combination seen to-date."
1Teng et al, Cancer Research 75(11) June 1, 2015
10-K – Annual report [Section 13 and 15(d), not S-K Item 405]
Syros Pharmaceuticals has filed a 10-K – Annual report [Section 13 and 15(d), not S-K Item 405] with the U.S. Securities and Exchange Commission (Filing, 10-K, Syros Pharmaceuticals, 2017, MAR 20, 2017, View Source [SID1234521276]).
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Checkpoint Therapeutics to Present Preclinical Data at the American Association for Cancer Research Annual Meeting 2017
On March 20, 2017 Checkpoint Therapeutics, Inc. ("Checkpoint") (OTCQX: CKPT), a Fortress Biotech (NASDAQ: FBIO) company, reported that preclinical data on its anti-PD-L1 antibody and EGFR inhibitor programs will be presented in poster sessions at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2017, to be held April 1-5, at the Walter E. Washington Convention Center in Washington, D.C (Press release, Fortress Biotech, MAR 20, 2017, View Source;FID=1001221494 [SID1234518214]).
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Details on the poster presentations are as follows:
Title: CK-101 (RX518), a mutant-selective inhibitor of EGFR that overcomes T790M-mediated resistance in NSCLC
When: Monday, April 3, 1 – 5 p.m. ET
Session Title: Growth Factor and Hormone Receptors as Therapeutic Targets
Location: Halls A-C, Poster Section 4
Abstract Number: 2078
Poster Number: 5
Title: Preclinical characterization of a novel fully human IgG1 anti-PD-L1 mAb CK-301
When: Tuesday, April 4, 1 – 5 p.m. ET
Session Title: Immunoconjugates and Antibodies
Location: Halls A-C, Poster Section 26
Abstract Number: 4606
Poster Number: 21
For additional information, please visit the AACR (Free AACR Whitepaper) website: www.aacr.org.
BioLineRx Provides Update on Phase 2 Open-Label Study for
BL-8040 as Novel Stem Cell Mobilization Treatment
On March 20, 2017 BioLineRx Ltd. (NASDAQ/TASE: BLRX), a clinical-stage biopharmaceutical company focused on oncology and immunology, reported partial results data from its open-label Phase 2 trial for BL-8040 as a novel monotherapy approach for the mobilization and collection of blood forming stem and progenitor cells from the peripheral blood (Press release, BioLineRx, MAR 20, 2017, View Source [SID1234518185]).
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The study consists of donor and patient pairs for allogeneic hematopoietic cell transplantation. The first part of the study, which is nearing completion, is intended to enroll an initial cohort of 10 donor and recipient pairs, consisting of patients with advanced hematological malignancies and their HLA-matched sibling donors. Interim results show that a single injection of BL-8040 mobilized sufficient amounts of cells required for transplantation at a level of efficacy similar to that achieved by using 4-6 injections of G-CSF, the current standard of care. Furthermore, all recipients transplanted so far have experienced a successful neutrophil engraftment. The recipients will be followed for one year to assess acute and chronic GVHD events. As for the donors, BL-8040 treatment was safe and well tolerated.
Philip Serlin, Chief Executive Officer of BioLineRx, stated, "We are very encouraged by these initial results of the Phase 2 clinical trial for assessing BL-8040, our lead oncology and hematology platform, as a single agent for hematopoietic stem cell mobilization for allogeneic transplantation. Hematopoietic stem cells are increasingly used as part of the treatment regimen for certain types of hematological cancers, as well as for severe anemia and immune deficiency disorders. These results, supporting BL-8040 as a one-day dosing and up-to-two-day collection regimen, for rapid mobilization of substantial amounts of stem cells, represent a significant improvement over the current standard of care, which requires four-to-six daily injections of G-CSF and one-to-four apheresis sessions. If there are no safety concerns regarding graft failure or rejection after the interim safety review of donor-recipient pairs participating in Part 1 of the study, we will continue with Part 2 of the study, which will permit enrollment of recipients with either matched sibling or haploidentical donors, up to a total enrollment in the study of 24 donor-recipient pairs. We are looking forward to the topline results expected by the end of 2017."
"We continue our efforts to maximize the potential of our unique BL-8040 oncology platform, with multiple clinical studies for additional indications up and running or expected to start in 2017, including several combination studies with immune checkpoint inhibitors and a registration study in stem-cell mobilization for autologous transplantation," added Mr. Serlin.
The Phase 2 open-label study is conducted in collaboration with the Washington University School of Medicine, Division of Oncology, and will enroll up to 24 donor/recipient pairs, aged 18-70. The trial is designed to evaluate the ability of BL-8040, as a single agent, to promote stem cell mobilization for allogeneic hematopoietic cell transplantation. On the donor side, the primary endpoint of the study is the ability of a single injection of BL-8040 to mobilize sufficient amounts of cells for transplantation following up to two apheresis procedures. On the recipient side, the study aims to evaluate the time to engraftment rate following transplantation of the BL-8040 collected graft.
The study will also evaluate the safety and tolerability of BL-8040 in healthy donors, as well as graft durability, the incidence of grade 2-4 acute and chronic GVHD, and other recipient related parameters in patients who have undergone transplantation of hematopoietic cells mobilized with BL-8040.
About BL-8040
BL-8040 is a short peptide for the treatment of acute myeloid leukemia, solid tumors, and certain hematological indications. It functions as a high-affinity antagonist for CXCR4, a chemokine receptor that is directly involved in tumor progression, angiogenesis, metastasis and cell survival. CXCR4 is over-expressed in more than 70% of human cancers and its expression often correlates with disease severity. In a number of clinical and pre-clinical studies, BL-8040 has shown robust mobilization of cancer cells from the bone marrow, thereby sensitizing these cells to chemo- and bio-based anti-cancer therapy, as well as a direct anti-cancer effect by inducing apoptosis. In addition, BL-8040 has also demonstrated robust stem-cell mobilization, including the mobilization of colony-forming cells, and T, B and NK cells. BL-8040 was licensed by BioLineRx from Biokine Therapeutics and was previously developed under the name BKT-140.
About Stem Cell Mobilization
High-dose chemotherapy followed by hematopoietic cell transplantation has become an established treatment modality for a variety of hematologic malignancies, including multiple myeloma, as well as various forms of lymphoma and leukemia. Modern peripheral stem-cell harvesting often replaces the use of traditional surgical bone marrow stem-cell harvesting. In the modern method, stem cells are mobilized from the bone marrow using granulocyte colony-stimulating factor (G-CSF), often with the addition of a mobilizing agent such as Plerixafor (Mozobil), harvested from the donor’s peripheral blood by apheresis, and infused to the patient after chemotherapy ablation treatment.
An allogeneic hematopoietic cell transplant involves matching a patient’s tissue type, specifically their human leukocyte antigen (HLA) tissue type, with that of a related or unrelated donor. HLA proteins are found on all cells of our body and are the main way the immune system tells the difference between our own cells and foreign cells. The closer the HLA match between a donor and recipient, the greater the chance a transplant will be successful. If the HLA match is not close enough, the donor’s immune system, which accompanies the donated stem cells, recognizes the HLA mismatch, and will attack the recipient’s tissues. This process is known as graft versus host disease (GVHD).
Approximately 70% of people with a hematological malignancy or bone marrow failure syndrome who need an allogeneic transplant have an HLA-identical sibling or unrelated donor available. For patients who need a stem cell transplant but do not have an HLA-matched related or unrelated donor, recent medical advances have made possible the use of a partially matched or haploidentical related donor. A haploidentical related donor is usually a 50% match to the recipient and may be the recipient’s parent, sibling or child.
The advantage of having a haploidentical transplant is that it increases the chance of finding a donor as almost everyone has at least one haploidentical relative. Relatives can usually be asked to donate stem cells much more quickly than unrelated volunteer donors, particularly when the volunteer donors live in other countries, thereby allowing transplants to be done in a more timely manner.
With improvements in medical treatment, complications of a haploidentical transplant, such as GVHD, rejection of the graft and slow recovery of the immune system appear not to be increased compared to transplants using HLA-matched related or unrelated donors. Since this is a relatively new approach to stem cell transplantation, a haploidentical transplant is a treatment option that is not offered at all treatment centers, but is becoming more common.