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AbbVie Announces New Data Evaluating Venetoclax in a Variety of Hematologic Malignancies at the 22nd European Hematology Association Congress

On June 12, 2017 AbbVie (NYSE: ABBV), a global biopharmaceutical company, reported that data from multiple clinical trials evaluating venetoclax, a first-in-class oral B-cell lymphoma-2 (BCL-2) inhibitor, will be presented at the 22nd European Hematology Association (EHA) (Free EHA Whitepaper) Annual Congress, June 22-25, in Madrid (Press release, AbbVie, JUN 12, 2017, View Source [SID1234519487]). Investigational data will be presented from 15 studies evaluating venetoclax across some of the most common hematologic malignancies, including chronic lymphocytic leukemia, multiple myeloma, acute myeloid leukemia and non-Hodgkin lymphoma.

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VENCLYXTO monotherapy is approved in the EU for the treatment of CLL in the presence of 17p deletion or TP53 mutation in adult patients who are unsuitable for or have failed a B-cell receptor pathway inhibitor; and for the treatment of CLL in the absence of 17p deletion or TP53 mutation in adult patients who have failed both chemoimmunotherapy and a B-cell receptor pathway inhibitor.1 VENCLYXTO is being developed by AbbVie and Roche. It is jointly commercialized by AbbVie and Genentech, a member of the Roche Group, in the U.S. and by AbbVie outside of the U.S.

"AbbVie is committed to investigating the safety and efficacy of venetoclax. The data being presented at EHA (Free EHA Whitepaper) reinforce this commitment and underscore our mission to develop and deliver therapies that address unmet needs in a selected set of debilitating hematologic malignancies and have a remarkable impact on the lives of people affected by cancer," said Gary Gordon, M.D., Ph.D., vice president, oncology clinical development, AbbVie.

AbbVie abstracts:

Venetoclax in CLL

Venetoclax in relapsed/refractory chronic lymphocytic leukemia (CLL) with 17p deletion: outcome and correlation with minimal residual disease from the full population of the pivotal M13-982 trial; Stilgenbauer et al.; Abstract S771; Oral Presentation; Sunday, June 25, 2017; 8:30-8:45 a.m. CEST
Treatment and 17p deletion testing patterns in community practice for patients with chronic lymphocytic leukemia (CLL) in the United States; Kapustyan et al.; Abstract E1023; ePOSTER; Friday, June 23, 2017; 8:30 a.m. CEST
Durability of responses on continuous therapy and following drug cessation in deep responders with venetoclax and rituximab; Anderson et al.; Abstract P247; Poster Presentation; Friday, June 23, 2017; 5:15-6:45 p.m. CEST
Attainment of complete remission is significantly associated with longer survival outcomes in relapsed/refractory (R/R) CLL: a meta-analysis; Ektare et al.; Abstract E1037; ePOSTER; Friday, June 23, 2017; 8:30 a.m. CEST
Impact of venetoclax on the quality of life of CLL patients relapsed/refractory to B-cell receptor (BCR) signaling pathway inhibitor treatment; Wierda et al.; Abstract P728; Poster Presentation; Saturday, June 24, 2017; 5:30-7:00 p.m. CEST
Impact of venetoclax on the quality of life of patients with relapsed/refractory chronic lymphocytic leukemia: results of a Phase 2, open-label study of venetoclax (ABT-199/GDC-0199) monotherapy; Wierda et al.; Abstract E1466; ePOSTER; Friday, June 23, 2017 8:30 a.m. CEST
Reduced healthcare resource utilization in patients with chronic lymphocytic leukemia achieving complete remission to first-line therapy; Enschede et al.; Abstract E1035; ePOSTER; Friday, June 23, 2017; 8:30 a.m. CEST
Progression-free survival (PFS) and overall survival (OS) in patients with chronic lymphocytic leukemia (CLL) — clinical benefits of achieving a deep response to first-line therapy; Samp et al.; Abstract PB1791; Publication; Thursday, May 18, 2017; 12:00 p.m. CEST

Venetoclax in AML

Safety and efficacy of venetoclax (VEN) in combination with decitabine or azacitidine in treatment-naive, elderly patients (>=65 years) with acute myeloid leukemia (AML); Pratz et al.; Abstract S472; Oral Presentation; Saturday, June 24, 2017; 4:15-4:30 p.m. CEST
Updated safety and efficacy results of Phase 1/2 study of venetoclax plus low-dose cytarabine in treatment-naive acute myeloid leukemia patients aged >=65 years and unfit for standard induction therapy; Wei et al.; Abstract S473; Oral Presentation; Saturday, June 24, 2017; 4:30-4:45 p.m. CEST

Venetoclax in NHL/MM

A Phase 1 study evaluating the safety and pharmacokinetics of venetoclax in Japanese patients with non-Hodgkin lymphoma and multiple myeloma; Yamamoto et al.; Abstract E1139; ePOSTER; Friday, June 23, 2017; 8:30 a.m. CEST

Venetoclax in MM

A Phase 1b study of venetoclax combined with bortezomib and dexamethasone in patients with relapsed/refractory multiple myeloma; Moreau et al.; Abstract s460; Oral Presentation; Saturday, June 24, 2017; 5:00-5:15 p.m. CEST
BCL2 expression is a potential predictive biomarker of response to venetoclax in combination with bortezomib and dexamethasone in patients with relapsed/refractory multiple myeloma; Ross et al.; Abstract P682; Poster Presentation; Saturday, June 24, 2017; 5:30-7:00 p.m. CEST
Venetoclax as targeted therapy for relapsed/refractory multiple myeloma; Kumar et al.; Abstract P675; Poster Presentation; Saturday, June 24, 2017; 5:30-7:00 p.m. CEST

Venetoclax in NHL

Venetoclax (VEN) in patients with relapsed/refractory non-Hodgkin lymphoma (NHL); Davids et al.; Abstract P564; Poster Presentation; Saturday, June 24, 2017; 5:30-7:00 p.m. CEST

The EHA (Free EHA Whitepaper) 2017 Annual Congress abstracts are available at www.ehaweb.org.

Propanc Biopharma Makes Significant Progress with PCT Patent Application

On June 9, 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 significant progress with yet another Patent Cooperation Treaty (PCT) patent application within its intellectual property (IP) portfolio (Press release, Propanc, JUN 9, 2017, View Source [SID1234519486]).

The Company received a Written Opinion from an International Search Authority regarding the novelty, inventive step and industrial applicability of the invention claimed in the recent PCT application, filed in April, 2017. The PCT application titled "Composition of Proenzymes for Cancer Treatment" is directed to a composition comprising trypsinogen and chymotrypsinogen, targeting specific weight ratios and certain dosage levels for the Company’s lead product, PRP. The majority of claims were considered novel and a number of claims considered inventive, as determined by the Authorized Officer from the Australian Patent Office. Furthermore, it appears that the experimental data included in the application and the way it is presented adequately supports the pending claims. The PCT assists applicants in seeking patent protection internationally for their inventions and the Written Opinion can guide national patent offices with their patent granting decisions. By filing one international patent application under the PCT, applicants can simultaneously seek protection for an invention in over 150 countries.

"We continue to make significant progress with our IP portfolio and look forward to entering the national phase where we will seek to obtain jurisdiction in key countries and regions, globally," said James Nathanielsz, Propanc Biopharma’s Chief Executive Officer. "We remain committed to further establishing ourselves as the lead player in a new and exciting field of oncology, using proenzymes as a means to halt progression of cancer from solid tumors. Hence, we continue to work hard along with our partner research organizations and scientific experts to explore new opportunities to expand our portfolio, and to also discover new treatments methods and compounds which even further enhances the effects of PRP."

The Company’s lead product, PRP, is a solution for once daily intravenous administration of a combination of two pancreatic proenzymes trypsinogen and chymotrypsinogen. 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.

XBiotech Announces Discontinuation of Phase III Study for Colorectal Cancer Based on Second Interim Analysis

On June 9, 2017 XBiotech Inc. (NASDAQ:XBIT) reported that an Independent Data Monitoring Committee (IDMC) has performed its second prospectively planned, unblinded analysis of the Phase 3 XCITE study for the Company’s novel candidate antibody therapy for the treatment of colorectal cancer (Press release, XBiotech, JUN 9, 2017, View Source [SID1234519485]). The IDMC had no safety concerns from the unblinded analysis. However, the committee recommended the early termination of the study since the findings were not sufficient to meet efficacy or the threshold for continuation, which involved a prospectively defined acceptance boundary for the interim analysis of less than or equal to p = 0.08.

John Simard, XBiotech President & CEO stated, "We are obviously disappointed with these findings. In the coming weeks, the Company plans to analyze the data extensively to further understand the primary and secondary endpoint data, as well as to identify populations that may have benefited from the therapy. These findings today will not affect our efforts to pursue approval of the therapy based on the successful completion of the European study, which demonstrated control of debilitating symptoms in colorectal cancer."

Patients enrolled in the XCITE study were randomized 2:1 to receive Xilonix or placebo plus, in each case, best supportive care. Advanced colorectal cancer patients were required to have previous failed regimens that included flouropyrimidines, oxaliplatin, irinotecan, and Cetuximab (or Panitumumab for patients with KRAS mutation). Patients were expected to continue in the study until there was evidence of radiographic progression. The patients were to be followed for up to 18 months in order to determine overall survival. The primary endpoint of this study was overall survival, with secondary endpoints including objective response rate, progression free survival, change in lean body mass and patient reported quality of life measures.

About True Human Therapeutic Antibodies
XBiotech’s True Human antibodies are derived without modification from individuals who possess natural immunity to certain diseases. With discovery and clinical programs across multiple disease areas, XBiotech’s True Human antibodies have the potential to harness the body’s natural immunity to fight disease with increased safety, efficacy and tolerability.

Astellas and Pfizer Announce Amendment to Clinical Research Protocol for Phase 3 PROSPER Trial of enzalutamide in Patients with Non-metastatic Castration-Resistant Prostate Cancer (pdf 446KB)

On June 9, 2017 Astellas Pharma Inc. (TSE: 4503, President and CEO: Yoshihiko Hatanaka, "Astellas") and Pfizer Inc. (NYSE: PFE) reported the amendment of the protocol for the registrational PROSPER trial, a multi-national, randomized, double-blind, placebo-controlled study evaluating the efficacy and safety of XTANDI (enzalutamide) in patients with non-metastatic (M0) Castration-Resistant Prostate Cancer (CRPC) (Press release, Astellas, JUN 9, 2017, View Source [SID1234519482]). The primary endpoint remains the same: metastasis-free survival (MFS). The main purpose of the amendment is to revise the plan for the analyses of the primary and several secondary endpoints, which allows for a reduction in the target sample size to approximately 1,440, from 1,560 patients. The companies now anticipate PROSPER top-line results will be disclosed later this year. Previously the expected primary completion date for PROSPER was June 2019.

"XTANDI is already a standard of care for men worldwide fighting metastatic castrationresistant prostate cancer, but we are continually looking to evaluate this medicine for men facing earlier stage disease," said Steven Benner, M.D., senior vice president and global therapeutic area head, oncology development, Astellas. "By amending the protocol for PROSPER, we hope to be able to accelerate the evaluation of the data in this area of medical need."

"PROSPER is one of a number of large, randomized trials in our robust, registration-focused development program, where we are evaluating enzalutamide in different prostate cancer populations, including men with earlier stages of the disease," said Mace Rothenberg, MD, chief development officer, Oncology, Pfizer Global Product Development. "We look forward to 2 building upon the extensive body of clinical evidence that has been generated over the past five years and established XTANDI as a standard of care for men with metastatic CRPC."

XTANDI is approved by the U.S. Food and Drug Administration for the treatment of patients with metastatic CRPC, based on clinical studies showing statistically significant overall survival benefit versus placebo.

Details regarding the protocol amendment for PROSPER (NCT02003924) will be available on ClinicalTrials.gov.

About XTANDI (enzalutamide) capsules
XTANDI (enzalutamide) is an androgen receptor inhibitor that blocks multiple steps in the androgen receptor signaling pathway within the tumor cell. In preclinical studies, enzalutamide has been shown to competitively inhibit androgen binding to androgen receptors, and inhibit androgen receptor nuclear translocation and interaction with DNA. The clinical significance of this mechanism of action (MOA) is unknown.

Important Safety Information

Contraindications XTANDI is not indicated for women. XTANDI can cause fetal harm and potential loss of pregnancy.

Warnings and Precautions
Seizure occurred in 0.5% of patients receiving XTANDI in clinical studies. In placebocontrolled studies, 8 of 1671 (0.5%) patients treated with XTANDI and 1 of 1243 (0.1%) patients treated with placebo experienced a seizure. In patients who previously received docetaxel, 7 of 800 (0.9%) patients treated with XTANDI experienced a seizure and no patients treated with placebo experienced a seizure. In a placebo-controlled study in chemotherapy-naïve patients, 1 of 871 (0.1%) treated with XTANDI and 1 of 844 (0.1%) patients treated with placebo experienced a seizure. In bicalutamide-controlled studies conducted in chemotherapy-naïve patients, 3 of 380 (0.8%) patients treated with XTANDI and 1 of 387 (0.3%) patients treated with bicalutamide experienced a seizure. Permanently discontinue XTANDI in patients who develop a seizure during treatment.

Posterior Reversible Encephalopathy Syndrome (PRES) In post approval use, there have been reports of PRES in patients receiving XTANDI. PRES is a neurological disorder which can present with rapidly evolving symptoms including seizure, headache, lethargy, confusion, blindness, and other visual and neurological disturbances, with or without associated hypertension. A diagnosis of PRES requires confirmation by brain imaging, preferably MRI. Discontinue XTANDI in patients who develop PRES.

Adverse Reactions
The most common adverse reactions (≥ 10%) that occurred more commonly (≥ 2% over placebo) in the XTANDI patients from the two placebo-controlled clinical trials were asthenia/fatigue, back pain, decreased appetite, constipation, arthralgia, diarrhea, hot flush, upper respiratory tract infection, peripheral edema, dyspnea, musculoskeletal pain, weight decreased, headache, hypertension, and dizziness/vertigo. In the bicalutamide-controlled study of chemotherapy naïve patients, the most common adverse reactions (≥ 10%) reported in XTANDI patients were asthenia/fatigue, back pain, musculoskeletal pain, hot flush, 3 hypertension, nausea, constipation, upper respiratory tract infection, diarrhea, and weight loss.

In the study of patients taking XTANDI who previously received docetaxel, Grade 3 and higher adverse reactions were reported among 47% of XTANDI patients and 53% of placebo patients. Discontinuations due to adverse events were reported for 16% of XTANDI patients and 18% of placebo patients. In the placebo-controlled study of chemotherapy-naïve patients, Grade 3-4 adverse reactions were reported in 44% of XTANDI patients and 37% of placebo patients. Discontinuations due to adverse events were reported for 6% of both study groups. In the bicalutamide-controlled study of chemotherapy naïve patients, Grade 3-4 adverse reactions were reported in 38.8% of XTANDI patients and 37.6% of bicalutamide patients. Discontinuations due to adverse events were reported for 7.6% of XTANDI patients and 6.3% of bicalutamide patients.

Lab Abnormalities: In the two placebo-controlled trials Grade 1-4 neutropenia occurred in 15% of XTANDI patients (1% Grade 3-4) and 6% of placebo patients (0.5% Grade 3-4). Grade 1-4 thrombocytopenia occurred in 6% of XTANDI patients (0.3% Grade 3-4) and 5% of placebo patients (0.5% Grade 3-4). Grade 1-4 elevations in ALT occurred in 10% of XTANDI patients (0.2% Grade 3-4) and 16% of placebo patients (0.2% Grade 3-4). Grade 1-4 elevations in bilirubin occurred in 3% of XTANDI patients (0.1% Grade 3-4) and 2% of placebo patients (no Grade 3-4).

Infections: In a study of patients taking XTANDI who previously received docetaxel, 1% of XTANDI patients compared to 0.3% of placebo patients died from infections or sepsis. In the placebo-controlled study of chemotherapy-naïve patients, 1 patient in each treatment group (0.1%) had an infection resulting in death.

Falls (including fall-related injuries) occurred in 9% of XTANDI patients and 4% of placebo patients in the two placebo-controlled trials. Falls were not associated with loss of consciousness or seizure. Fall-related injuries were more severe in XTANDI patients, and included non-pathologic fractures, joint injuries, and hematomas. Hypertension occurred in 11% of XTANDI patients and 4% of placebo patients in the two placebo-controlled trials. No patients experienced hypertensive crisis. Medical history of hypertension was balanced between arms. Hypertension led to study discontinuation in < 1% of all patients in each arm.

Drug Interactions
Effect of Other Drugs on XTANDI Avoid strong CYP2C8 inhibitors, as they can increase the plasma exposure to XTANDI. If co-administration is necessary, reduce the dose of XTANDI. Avoid strong CYP3A4 inducers as they can decrease the plasma exposure to XTANDI. If coadministration is necessary, increase the dose of XTANDI.

Effect of XTANDI on Other Drugs Avoid CYP3A4, CYP2C9, and CYP2C19 substrates with a narrow therapeutic index, as XTANDI may decrease the plasma exposures of these drugs. If XTANDI is co-administered with warfarin (CYP2C9 substrate), conduct additional INR monitoring.

Inovio Begins Phase 3 Clinical Trial of VGX-3100 for the Treatment of HPV-Related Cervical Pre-Cancer

On June 8, 2017 Inovio Pharmaceuticals, Inc. (NASDAQ:INO) reported that it has commenced its phase 3 clinical program to evaluate the efficacy of Inovio’s DNA-based immunotherapy, VGX-3100, to treat cervical dysplasia caused by human papillomavirus (HPV) (Press release, Inovio, JUN 8, 2017, View Source [SID1234519479]). Inovio’s study will assess the efficacy of VGX-3100 in regressing cervical HSIL (high-grade squamous intraepithelial lesions), a direct precursor to cervical cancer, and eliminating the HPV infection that causes these lesions. The pivotal data from this program will support the potential licensure of VGX-3100 as the first immunotherapy for this disease.

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Inovio satisfied the FDA’s request for information relating to its CELLECTRA 5PSP delivery device, resulting in the FDA removing the clinical hold on this program. Inovio plans to immediately begin recruiting patients for the phase 3 trial.

Inovio’s phase 3 program, named REVEAL (Randomized Evaluation of VGX-3100 and Electroporation for the Treatment of Cervical HSIL), will consist of a primary study (REVEAL 1) and confirmatory study (REVEAL 2), as per FDA general guidance for phase 3 programs, to be conducted in parallel. The studies will each enroll 198 patients in more than 100 study centers globally. Mark Einstein, MD, MS, FACS, FACOG, Professor and Chair Department of Obstetrics, Gynecology and Women’s Health Assistant Dean, Clinical Research Unit, Rutgers New Jersey Medical School, is Principal Investigator for the studies.

The REVEAL studies are prospective, randomized (2:1), double-blind, placebo-controlled trials evaluating adult women with HPV 16/18 positive biopsy-proven cervical HSIL, otherwise known as cervical intraepithelial neoplasia (CIN) 2 or 3. The primary endpoint is regression of cervical HSIL AND virologic clearance of HPV-16 and/or HPV-18 in the cervix. The studies will evaluate cervical tissue changes at approximately 9 months after beginning a three dose regimen of VGX-3100 administered at months 0, 1, and 3. Secondary endpoints include safety; tolerability; regression of CIN 2/3 to CIN 1 or normal; virologic clearance of HPV; efficacy measured by non-progression to cancer; and clearance of HPV from non-cervical anatomic locations.

VGX-3100 has the potential to be the first treatment for HPV infection of the cervix and the first non-surgical treatment for pre-cancerous cervical lesions. VGX-3100 stimulates a specific immune response to HPV-16 and HPV-18, targeting the infection and destroying pre-cancerous cells. There are no treatments available for HPV infection and surgery is the only approved treatment for cervical HSIL. While surgery is effective at removing dysplastic lesions, it does not treat the underlying HPV infection and carries increased risk of cervical incompetence and pre-term birth, which can result in fetal morbidity and mortality. VGX-3100 demonstrated in a phase 2b study (published in The Lancet) its ability to clear HPV-16 and HPV-18 infection and pre-cancerous lesions.

Dr. Mark Bagarazzi, Inovio’s Chief Medical Officer, said, "Despite the availability of preventive HPV vaccines for over a decade, HPV-related cervical HSIL and cancers remain a widely prevalent problem. Unfortunately, current treatments are invasive and do not address the underlying HPV infection. VGX-3100 has the potential to be a first-in-class HPV-specific immunotherapy offering women the prospect of preventing cervical cancer without undergoing an invasive surgical procedure that may compromise their reproductive health. We are pleased to be able to immediately begin recruiting patients at the first 15 sites by the end of this month."

Dr. J. Joseph Kim, Inovio’s President and CEO, said, "Initiating our REVEAL phase 3 program marks a milestone for Inovio, for the next generation of DNA-based immunotherapies, and for women’s health. Combining this first phase 3 program with our previously announced phase 2 clinical trial of VGX-3100 for HPV-related vulvar neoplasia and our checkpoint inhibitor-based combination study with MedImmune/AstraZeneca targeting HPV associated cancers, Inovio is well positioned to comprehensively treat HPV-associated diseases across the continuum of HPV infection through to cancer in both men and women. Adding our recently announced collaborative immuno-oncology combination studies with Regeneron and Genentech, 2017 is a transformative year that is laying the foundation for multiple opportunities for important efficacy data."

About HPV and Cervical HSIL

HPV is the most common sexually transmitted infection, with over 14 million new infections annually. While many of these are transient infections, persistent high-risk infections can cause the formation of pre-cancerous lesions. Left untreated, women diagnosed with cervical HSIL are at increased risk of developing cervical cancer. HPV types 16 and 18 are responsible for 70% of cervical cancers, with more than 400,000 new cases of HPV 16/18 cervical HSIL annually in the US and Europe. Cervical cancer is a major global health problem, causing 260,000 deaths annually. While cervical HSIL and cervical cancer are the most well-known HPV related diseases, HPV is also a major cause of HSIL and cancer in the entire anogenital region and oropharynx. Currently there are no treatments available for HPV infection and surgery is the only approved treatment for cervical HSIL. While surgery is effective at removing lesions, it does not treat the underlying HPV infection and it carries increased risk of cervical incompetence and pre-term birth, which can result in fetal morbidity and mortality.

About VGX-3100

VGX-3100 is a DNA-based immunotherapy under investigation for the treatment of HPV-16 and HPV-18 infection and pre-cancerous lesions of the cervix (phase 3) and vulva (phase 2). VGX-3100 has the potential to be the first approved treatment for HPV infection of the cervix and the first non-surgical treatment for pre-cancerous cervical lesions. VGX-3100 works by stimulating a specific immune response to HPV-16 and HPV-18, which targets the infection and causes destruction of pre-cancerous cells. In a randomized, double-blind, placebo-controlled phase 2b study in 167 adult women with histologically documented HPV 16/18 cervical HSIL (CIN2/3), treatment with VGX-3100 resulted in a statistically significantly greater decrease in cervical HSIL and clearance of HPV infection vs. placebo. The most common side effect was injection site pain, and no serious adverse events were reported. VGX-3100 utilizes the patient’s own immune system to clear HPV-16 and HPV-18 infection and pre-cancerous lesions without the increased risks associated with surgery, such as loss of reproductive health and negative psychosocial impacts.