On October 25, 2017 Actinium Pharmaceuticals, Inc. (NYSE MKT:ATNM) ("Actinium" or "the Company"), a clinical-stage biopharmaceutical company focused on developing and commercializing targeted therapies for safer myeloablation and conditioning of the bone marrow prior to a bone marrow transplant (BMT) and for the targeting and killing of cancer cells reported that the Company has successfully activated fifteen clinical trial sites in the pivotal Phase 3 SIERRA (Study of Iomab-B in Elderly Relapsed or Refractory Acute Myeloid Leukemia) trial (Press release, Actinium Pharmaceuticals, OCT 25, 2017, View Source [SID1234521146]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

The SIERRA trial is planned to enroll 150 patients with relapsed or refractory acute myeloid leukemia (AML) who are age 55 and above and will compare Iomab-B and a BMT to physician’s choice of salvage chemotherapy. The primary end point is durable complete remission (dCR) of at least 6 months. Iomab-B is intended to provide safer myeloablation of the bone marrow prior to a bone marrow transplant, thus providing a potentially curative treatment option for this patient population and for patients with other leukemias, lymphomas, myelomas and other blood disorders. The following medical institutions are clinical trial sites in the Iomab-B Phase 3 clinical trials:

Center Location
MD Anderson Cancer Center Houston, Texas
Memorial Sloan Kettering Cancer Center New York, New York
Mayo Clinic Rochester, Minnesota
Mayo Clinic Jacksonville, Florida
Washington University School of Medicine Saint Louis, Missouri
Yale Cancer Center New Haven, Connecticut
Baylor Charles A. Sammons Cancer Center Dallas, Texas
The University of Kansas Cancer Center Westwood, Kansas
Roswell Park Cancer Institute Buffalo, New York
University Hospitals Cleveland Medical Center Cleveland, Ohio
The Ohio State University Comprehensive Cancer Center Columbus, Ohio
Penn State Hershey Cancer Institute Hershey, Pennsylvania
Loyola University Medical Center Maywood, Illinois
Banner MD Anderson Cancer Center Gilbert, Arizona
Fred Hutchinson Cancer Research Center Seattle, Washington
Dr. Mark Berger, Actinium’s Chief Medical Officer said, "I am delighted to be working with these world-renowned investigators and institutions in this important SIERRA trial for Iomab-B. Their interest and enthusiasm for Iomab-B further motivates my team as we work on this trial to bring Iomab-B to patients who could benefit from safer myeloablation prior to a bone marrow transplant. In many blood cancers and disorders a bone marrow transplant is the only potentially curative treatment option for patients and it is our goal to improve outcomes for these patients with Iomab-B by getting them to their transplant faster and with less complications than currently available myeloablative regimens allow. We are looking forward to adding additional clinical trial sites located in the U.S. and Canada to make this trial available to a greater range of patients and to expedite completion of the trial."

Actinium also announced that it will provide an update on the Iomab-B SIERRA trial by year end. The SIERRA trial will have three safety analyses by an independent Data Monitoring Committee when 25%, 50% and 75% patient enrollment has been reached. Also, two ad-hoc efficacy analyses may be requested by Actinium after 70 and/or 110 patients have engrafted and given enough time to achieve the primary endpoint of durable complete remission at six months post treatment.

Sandesh Seth, Actinium’s Chairman & CEO said, "Until this trial, Iomab-B had only been studied in a single center and Actinium is proud to have facilitated use of this important therapeutic option in most of the leading transplant centers in the U.S. via the SIERRA trial. These fifteen centers perform approximately a third of all AML related bone marrow transplants. Our ability to introduce Iomab-B in these centers bodes well for enrollment in the trial and also the commercial opportunity for Iomab-B as the top fifty centers account for approximately eighty percent of bone marrow transplants. There is no visible competition for Iomab-B from any drug or drug candidate that can provide safer myeloablation and enable improved outcomes of bone marrow transplant. Actinium intends to build on the clinical experience, infrastructure and supply chain capabilities that we have established thus far to complete the trial in accordance with prior guidance and, assuming a successful outcome, establish Iomab-B as the standard of care in providing safer myeloablation first in in AML and then in the other hematologic indications in which it has shown positive results."

About Iomab-B

Iomab-B is Actinium’s lead product candidate that is currently being studied in a 150-patient, multicenter pivotal Phase 3 clinical trial in patients with relapsed or refractory acute myeloid leukemia who are age 55 and above. 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, which 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 patients experienced transplant engraftment at day 28. Iomab-B was developed at the Fred Hutchinson Cancer Research Center where it has been studied 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). 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.

On October 26, 2017 Roche (SIX: RO, ROG; OTCQX: RHHBY) reported that the U.S. Food and Drug Administration (FDA) has accepted the company’s supplemental Biologics License Application (sBLA) for Avastin (bevacizumab) in combination with chemotherapy (carboplatin and paclitaxel), followed by Avastin alone, for the front-line treatment of women with advanced ovarian cancer (Press release, Hoffmann-La Roche, OCT 25, 2017, View Source [SID1234521187]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

“About 80 percent of women with ovarian cancer are diagnosed in the advanced stages when the disease is difficult to treat and options are limited,” said Sandra Horning, M.D., chief medical officer and head of Global Product Development. “We are committed to working closely with the FDA to bring this potential new treatment option to women with newly diagnosed advanced ovarian cancer as soon as possible.”

This sBLA for Avastin, in combination with carboplatin and paclitaxel, followed by Avastin as a single agent, for the front-line treatment of people with advanced epithelial ovarian, fallopian tube, or primary peritoneal cancer, is based on data from the pivotal Phase III GOG-0218 trial. In newly diagnosed advanced ovarian cancer, the first treatment a woman receives after surgery is known as front-line treatment. The FDA is expected to make a decision on approval by June 25, 2018.

This is part of our broader development program for Avastin in ovarian cancer. Avastin is currently approved for treating two different forms of advanced disease that recurred after platinum-based chemotherapy. In addition, Genentech is evaluating Avastin in combination with Tecentriq (atezolizumab) and chemotherapy for the treatment of newly diagnosed advanced ovarian cancer in the Phase III IMagyn050 trial (NCT03038100).

About the GOG-0218 Study
GOG-0218 (NCT00262847) is a multi-center, randomized, double-blind, placebo-controlled Phase III study in 1,873 women with previously untreated advanced epithelial ovarian, primary peritoneal, or fallopian tube carcinoma who already had surgery to remove as much of the tumor as possible. Participants were randomized into one of three treatment arms: chemotherapy alone (carboplatin and paclitaxel), Avastin (15 mg/kg) plus chemotherapy followed by placebo alone, or Avastin plus chemotherapy followed by Avastin alone. Women who received Avastin in combination with chemotherapy, and continued use of Avastin alone for a total duration of 22 cycles, had a median progression-free survival (PFS) of 18.2 months compared to 12.0 months in women who received chemotherapy alone (HR=0.64; 95% CI 0.54 – 0.77, p<0.0001). Secondary endpoints of the study included overall survival (OS) and objective response rate (ORR). Adverse events were consistent with those seen in previous trials of Avastin across tumor types for approved indications. The study was conducted by the Gynecologic Oncology Group (GOG) and their initial results were previously published in the New England Journal of Medicine.

About Ovarian Cancer
Ovarian cancer causes more deaths among women than any other gynecologic cancer in the United States. In 2017, nearly 22,000 women will be diagnosed with ovarian cancer in the U.S. and more than 14,000 will die from the disease. About 80% of ovarian cancer cases are found at an advanced stage, when the cancer has spread beyond the ovaries. Early ovarian cancer often does not have any symptoms and when symptoms, such as abdominal swelling, bloating, abdominal pain, difficulty eating or feeling full quickly, and/or frequent urination, are present, they can be associated by other less serious conditions. Five-year survival rates worsen dramatically based on stage of diagnosis.

About Avastin
With the initial approval in the United States for advanced colorectal cancer in 2004, Avastin became the first anti-angiogenic therapy made widely available for the treatment of patients with an advanced cancer.
Today, Avastin is continuing to transform cancer care through its proven survival benefit (overall survival and/or progression free survival) across several types of cancer. Avastin is approved in Europe for the treatment of advanced stages of breast cancer, colorectal cancer, non-small cell lung cancer, kidney cancer, ovarian cancer and cervical cancer, and is available in the United States for the treatment of colorectal cancer, non-small cell lung cancer, kidney cancer, cervical cancer and recurrent, platinum-resistant and platinum-sensitive ovarian cancer. In addition, Avastin is approved over 70 other countries worldwide for the treatment of patients with progressive glioblastoma following prior therapy. Avastin is approved in Japan for the treatment of the advanced stages of colorectal cancer, non-small cell lung cancer, breast cancer, ovarian cancer and malignant glioma, including newly diagnosed glioblastoma.
Avastin has made anti-angiogenic therapy a fundamental pillar of cancer treatment today. Over two million patients have been treated with Avastin so far. A comprehensive clinical programme with more than 300 ongoing clinical trials is investigating the use of Avastin in over 50 tumour types.

On October 26, 2017 Evotec AG (Frankfurt Stock Exchange: EVT, TecDAX, ISIN: DE0005664809) and TESARO, Inc. (“TESARO”) reported a three-year integrated drug discovery collaboration to discover and develop novel small molecule product candidates against an undisclosed immuno-oncology (IO) target (Press release, Evotec, OCT 25, 2017, View Source [SID1234521186]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

Under the terms of the collaboration, Evotec will apply its integrated drug discovery platform, from lead discovery through nomination of a pre-clinical development candidate, to TESARO’s translational research pipeline to advance best-in-class oncology therapies. In particular, Evotec will leverage its industry leading structural biology platform to identify novel start points to progress into a full-blown drug discovery programme.

“TESARO is excited to work with Evotec to expand our discovery capabilities against immuno-oncology targets”, said Jeffrey Hanke, Ph.D., Executive Vice President, Research and Development, and Chief Scientific Officer of TESARO. “Evotec has a proven track record of enhancing its partners’ drug discovery efforts in oncology. We look forward to working with Evotec to accelerate the identification of new therapies to help patients facing cancer.”

Dr Mario Polywka, Chief Operating Officer of Evotec, commented: “Oncology is one of Evotec’s core therapeutic areas of focus and we are pleased to enter into this exciting and innovative partnership with TESARO, a globally recognised oncology leader and one of the fastest growing biotech companies in the USA. This collaboration further demonstrates the value of our integrated research site in Toulouse and our world-leading structural biology group in Oxford. Using our integrated drug discovery platform, we are committed to helping TESARO drive innovation in this very important field of high-unmet medical need.”
No financial details of the collaboration were disclosed.

On October 25, 2017 Propanc Biopharma Inc. (OTCQB: PPCB) (“Propanc Biopharma” or “the Company”), a clinical stage biopharmaceutical company focusing on development of new and proprietary treatments for cancer patients suffering from solid tumors such as pancreatic, ovarian and colorectal cancers, reported it has submitted a request for Orphan Drug Designation (ODD) to the US Food and Drug Administration (FDA) for PRP, a solution for once daily intravenous administration of a combination of two pancreatic proenzymes trypsinogen and chymotrypsinogen (Press release, Propanc, OCT 25, 2017, View Source [SID1234521163]). The proposed orphan drug indication for PRP is the treatment of ovarian cancer.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

“Obtaining orphan drug designation from the FDA for our PRP therapy for ovarian cancer is a significant regulatory milestone that we are looking forward to, and will be a positive step forward in Propanc Biopharma’s ongoing efforts to develop effective treatments for metastatic cancer,” said James Nathanielsz, Propanc Biopharma’s Chief Executive Officer. “This will further reinforce our strategic investment in PRP, since we already achieved ODD status for pancreatic cancer, demonstrating significant progress in developing a potential best in class therapy that could transform treatment for patients with metastatic cancers, where limited treatment options are available. At the time the ODD is granted, we expect to be working closely with the regulatory authorities and clinical trial investigators to advance PRP promptly through the next stages of clinical development, ultimately filing a clinical trial application for First-In-Human studies in the UK early next year.”

Ovarian cancer is a disease with the lowest survival rate of all gynecological cancers, making it the seventh most common cause of cancer death in women worldwide. More than 60% of women present with stage III or stage IV metastasized cancer at the time of first diagnosis and have a five-year survival of less than 20%. The therapy is very complex and presupposes expertise in both surgery and oncology. Thus, to date therapy of ovarian cancer is a challenge and prognosis is rather poor, creating a high unmet medical need for new efficacious and safe treatment options.

Under the Orphan Drug Act (ODA), drugs, vaccines, and diagnostic agents qualify for orphan status if they are intended to treat a disease affecting less than 200,000 American citizens. Under the ODA, orphan drug sponsors qualify for seven-year FDA-administered market Orphan Drug Exclusivity (ODE), tax credits of up to 50% of R&D costs, R&D grants, waived FDA fees, protocol assistance and may get clinical trial tax incentives.

The rationale for developing PRP, a formulation of the pancreatic proenzymes trypsinogen and chymotrypsinogen for intravenous administration, in the proposed indication ovarian cancer is based on a set of in-vitro studies on cancer stem cells generated from various cancer cell lines as well as xenograft and orthotopic mouse models of ovarian cancer. In summary, these data indicate that the dramatic reduction of cellular markers associated with the process of epithelial-mesenchymal transition (EMT) as a consequence of PRP treatment can not only reverse the EMT process with the implication to stop tumor progression and metastasis, but also seem to repress the development of cancer stem cells (CSCs). Consequently, these results are strong indicators of the therapeutic potential of PRP that could be categorized as an anti-CSC therapeutic drug.

Further, recent scientific evidence demonstrates that EMT and CSCs play important roles in ovarian cancer chemoresistance, one of the main challenges in the treatment of recurrent ovarian cancer and responsible for the unfavourable outcome of this disease. Treatment of EMT and CSCs thus holds promise for improving current ovarian cancer therapies and prolonging the survival of recurrent ovarian cancer patients.

Preliminary early clinical data on the treatment of six patients with ovarian cancer have also been obtained using the two pancreatic proenzymes in the context of a UK “Specials” License treatment. Together, these data support the medical plausibility of the proposed indication and a distinctive benefit-safety profile of PRP for the treatment of ovarian cancer.

Currently progressing towards First-In-Human studies, PRP aims to prevent tumor recurrence and metastasis from solid tumors. Eighty percent of all cancers are solid tumors and metastasis is the main cause of patient death from cancer. According to the World Health Organization, 8.2 million people died from cancer in 2012. Consequently, a report by IMS Health states innovative therapies are driving the global oncology market to meet demand, which is expected to reach $150 Billion by 2020. The Company’s initial target patient populations are pancreatic, ovarian and colorectal cancers, representing a combined market segment of $14 Billion predicted in 2020, by GBI Research.

To view Propanc Biopharma’s “Mechanism of Action” video on anti-cancer product candidate, PRP, please click on the following link: View Source

To be added to Propanc Biopharma’s email distribution list, please click on the following link: View Source and submit the online request form.

GSK delivers Q3 sales of £7.8 billion, +4% AER, +2% CER (Press release, GlaxoSmithKline, OCT 25, 2017, View Source [SID1234521161]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

Total EPS 24.8p, +49% AER, +46% CER; Adjusted EPS 32.5p, +3% AER, flat CER


Financial highlights


●
Sales growth in Pharmaceuticals and Consumer Healthcare; Vaccines sales flat

●
Pharmaceuticals sales £4.2 billion +3% AER, +2% CER; Vaccines £1.7 billion +5% AER, flat at CER; Consumer Healthcare £2.0 billion +5% AER, +2% CER

●
Improved Total operating margin of 23.9% (+4.9 points, including 0.2 points currency benefit) and EPS (24.8p), primarily reflecting reduced transaction-related charges related to valuations of Consumer Healthcare and HIV businesses

●
Improved Adjusted Group operating margin of 31.5% (+1.0 point, no currency effect) primarily reflecting leverage from sales growth, focus on costs and benefits of restructuring. Pharmaceuticals 34.0% (-0.3 points, no currency effect); Vaccines 41.3% (+1.6 points, including 0.3 points adverse currency effect); Consumer Healthcare 20.0% (+3.9 points, including 1.3 points currency benefit)

●
YTD free cash flow £1.6 billion (9 months 2016: £1.3 billion)

●
19p dividend declared for quarter. Continue to expect 80p for FY 2017

●
Guidance for 2017 Adjusted earnings per share growth maintained at 3% to 5% CER

Product and pipeline highlights


●
New product sales of £1.7 billion, +44% AER, +40% CER, driven by continued strong performance from Tivicay/Triumeq in HIV, Relvar/Breo Ellipta and Nucala in Respiratory and meningitis vaccines

●
Trelegy Ellipta approved in the US for COPD and positive opinion received in Europe. Positive results from landmark IMPACT study show benefits of Trelegy Ellipta in reducing COPD exacerbations compared to dual therapies

●
Shingrix vaccine for shingles approved in US and Canada

●
Phase III results for Nucala (mepolizumab) in COPD published in New England Journal of Medicine with regulatory filings planned for this year

●
In Oncology, CHMP PRIME designation granted for 2857916 (BCMA antibody-drug conjugate) for relapsed and refractory multiple myeloma and new data to be presented at an upcoming scientific conference; option exercised from Adaptimmune to develop T-cell therapy (NY-ESO-1) for multiple tumour types