Uncategorized – Page 17959 – 1stOncology™: Cancer Intelligence Service

The Human Autoantibody Response to Apolipoprotein A-I Is Focused on the C-Terminal Helix: A New Rationale for Diagnosis and Treatment of Cardiovascular Disease?

Cardiovascular disease (CVD) is the leading cause of death worldwide and new approaches for both diagnosis and treatment are required. Autoantibodies directed against apolipoprotein A-I (ApoA-I) represent promising biomarkers for use in risk stratification of CVD and may also play a direct role in pathogenesis.
To characterize the anti-ApoA-I autoantibody response, we measured the immunoreactivity to engineered peptides corresponding to the different alpha-helical regions of ApoA-I, using plasma from acute chest pain cohort patients known to be positive for anti-ApoA-I autoantibodies.
Our results indicate that the anti-ApoA-I autoantibody response is strongly biased towards the C-terminal alpha-helix of the protein, with an optimized mimetic peptide corresponding to this part of the protein recapitulating the diagnostic accuracy for an acute ischemic coronary etiology (non-ST segment elevation myocardial infarction and unstable angina) obtainable using intact endogenous ApoA-I in immunoassay. Furthermore, the optimized mimetic peptide strongly inhibits the pathology-associated capacity of anti-ApoA-I antibodies to elicit proinflammatory cytokine release from cultured human macrophages.
In addition to providing a rationale for the development of new approaches for the diagnosis and therapy of CVD, our observations may contribute to the elucidation of how anti-ApoA-I autoantibodies are elicited in individuals without autoimmune disease.

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!

JNJ-63709178

JNJ-63709178, a bispecific antibody that targets CD3 and CD123, was created under a collaboration between Genmab and Janssen using Genmab’s DuoBody technology (Company Pipeline, Genmab, APR 26, 2016, View Source [SID:1234511406]). JNJ-63709178 is being investigated in a Phase I clinical study to treat relapsed or refractory acute myeloid leukemia and is the second bispecific antibody created with the DuoBody technology to be added to Genmab’s pipeline.

A multicenter, randomized, double-blind, placebo-controlled study to evaluate the efficacy and safety of treatment with sirukumab (CNTO 136) in patients with active lupus nephritis.

To assess sirukumab, an anti-interleukin-6 monoclonal antibody, for treatment of active lupus nephritis (LN).
Patients with Class III or IV LN (renal biopsy within 14 months of randomization), persistent proteinuria (≥0.5 g/d) despite immunosuppression, and stable renin-angiotensin system blockade were randomized (5:1) to receive intravenous sirukumab 10 mg/kg (n=21) or placebo (n=4) every 4 weeks through week 24. The primary endpoint was percent reduction of proteinuria (measured as the protein/creatinine ratio in a 12-hour urine collection) from baseline to week 24.
Twenty-five patients were enrolled; 19 (76.0%) completed treatment through week 24, and 6 (24.0%) discontinued the study agent early, 5 due to adverse events. At week 24, the median percent change in proteinuria from baseline in sirukumab-treated patients was 0.0% (95% CI: -61.8, 39.6). In contrast, the 4 placebo patients showed a median percent increase in proteinuria of 43.3% at week 24. Of note, a subset of 5 sirukumab-treated patients had ≥50% improvement in their protein/creatinine ratio through week 28. In the sirukumab group, 47.6% of patients had ≥1 serious adverse event; most were infection-related. No deaths or malignancies occurred. No serious adverse events were observed in the four placebo-treated patients.
This proof-of-concept study did not demonstrate the anticipated efficacy or an acceptable safety profile following sirukumab treatment in this population of patients with active LN receiving concomitant immunosuppressive treatment. This article is protected by copyright. All rights reserved.
© 2016, American College of Rheumatology.

Tokai Announces Oral Presentation on Galeterone at the 2016 AUA Annual Meeting

On April 26, 2016 Tokai Pharmaceuticals Inc. (NASDAQ: TKAI), a biopharmaceutical company focused on developing and commercializing innovative therapies for prostate cancer and other hormonally driven diseases, reported an oral presentation on galeterone at the 2016 American Urological Association (AUA) Annual Meeting in San Diego (Press release, Tokai Pharmaceuticals, APR 26, 2016, View Source;p=RssLanding&cat=news&id=2161338 [SID:1234511407]). Galeterone, Tokai’s lead product candidate, is being developed for the treatment of men with metastatic castration-resistant prostate cancer.

The presentation, titled "Galeterone shows anti-tumor activity in multiple pre-clinical models that express androgen receptor splice variants, supporting correlative patient data seen in ARMOR2" (abstract number PD32-07), will be presented on Sunday, May 8, from 4:30 – 4:40 p.m. PDT in room 30DE, as part of the session, "Prostate Cancer: Advanced (including Drug Therapy) III." The presenting author is Vincent C.O. Njar, Ph.D., Professor of Medicinal Chemistry and Pharmacology, Department of Pharmacology; Head of the Medicinal Chemistry Section, Center for Biomolecular Therapeutics; and Member of the Marlene and Stewart Greenebaum Cancer Center at the University of Maryland School of Medicine, Baltimore. Dr. Njar is a co-inventor of galeterone.

Additional information, including the presentation schedule and full abstracts, may be found at www.aua2016.org. A copy of the presentation will be available on the "Publications & Presentations" page of Tokai’s website, www.tokaipharmaceuticals.com.

About Galeterone
Galeterone is an oral small molecule that utilizes the established pathways, including CYP17 enzyme and androgen receptor inhibition, of the current second-generation hormonal therapies abiraterone and enzalutamide. Galeterone also introduces a distinct third mechanism – androgen receptor degradation – that decreases the sensitivity of androgen receptors to androgen activity, thus leading to reductions in tumor growth. Tokai is developing galeterone for the treatment of patients with metastatic castration-resistant prostate cancer (mCRPC). ARMOR3-SV, the company’s pivotal Phase 3 study of galeterone in treatment-naive mCRPC patients whose prostate tumors express the AR-V7 splice variant, is evaluating whether administration of galeterone results in a statistically significant increase in radiographic progression-free survival as compared to enzalutamide. Tokai is also evaluating galeterone in mCRPC patients who have shown resistance following treatment with second-generation hormonal agents. Tokai has worldwide development and commercialization rights to galeterone.

Defibrotide for Treatment of Severe Veno-Occlusive Disease in Pediatrics and Adults: An Exploratory Analysis Using Data from the CIBMTR.

Veno-occlusive disease (VOD) is an early and serious complication of hematopoietic cell transplantation (HCT) that is associated with inferior survival, particularly when it is complicated by multi-organ failure (severe VOD). We evaluated the efficacy of defibrotide in the treatment of severe VOD using observational data from the Center for International Blood and Marrow Transplant Research (CIBMTR). Eight thousand three hundred forty-one patients treated by HCT between 2008 and 2011 were identified from the CIBMTR clinical database; 3.2% met criteria for VOD and 1.2% met criteria for severe VOD. Patients with a diagnosis of VOD as reported to the CIBMTR by their transplanting centers, who had no prior history of cirrhosis, and who had a maximum total bilirubin &gt;2.0mg/dl by day +100 post-HCT were selected for study. Severe VOD was defined as VOD occurring in the setting of renal impairment requiring dialysis or any non-infectious pulmonary abnormality. Patients with severe VOD were divided into two groups for analysis: those treated with defibrotide (n=41) and those not treated with defibrotide (n=55). Patients in the non-defibrotide group were older, were more likely to be male, were more likely to have a history of previous fungal infection, and had a higher proportion of clinically significant pre-existing disease or organ impairment. Survival at day +100 was 39% (95% CI: 24.8-54.3%) in patients receiving defibrotide and 30.9% (95% CI: 19.5% – 43.6%) in those not receiving defibrotide. Resolution of VOD at day +100 was 51% in the defibrotide group, and 29% in the non-defibrotide group (difference 22.1%, 95% CI: 2.6% – 42%). The results of our study are consistent with previously reported experiences with defibrotide, confirm the poor outcome of this syndrome, and suggest defibrotide is effective in the treatment of severe VOD.
Copyright © 2016 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

1stOncology is recognized as a
Top 10 Global Pharma Analytic Provider

Continue your journey with 1stOncology by accessing our Free Leading Cancer Conference Whitepapers, signing up for our Free Weekly Newsletter and requesting a Free Demo to see how we can help you be 1st in Oncology!

Category: Uncategorized

The Human Autoantibody Response to Apolipoprotein A-I Is Focused on the C-Terminal Helix: A New Rationale for Diagnosis and Treatment of Cardiovascular Disease?

JNJ-63709178

A multicenter, randomized, double-blind, placebo-controlled study to evaluate the efficacy and safety of treatment with sirukumab (CNTO 136) in patients with active lupus nephritis.

Tokai Announces Oral Presentation on Galeterone at the 2016 AUA Annual Meeting

Defibrotide for Treatment of Severe Veno-Occlusive Disease in Pediatrics and Adults: An Exploratory Analysis Using Data from the CIBMTR.