Genta Incorporated (OTCBB: GETA) announced top-line results from AGENDA, the Company’s Phase 3 trial of Genasense® (oblimersen sodium) Injection in patients with advanced melanoma. AGENDA is a randomized, double-blind, placebo-controlled trial of dacarbazine administered with or without Genasense® in patients who have not previously received chemotherapy. As defined in a prior randomized trial, AGENDA uses a biomarker to define patients who might maximally benefit from treatment.

AGENDA did not show a statistically significant benefit for its co-primary endpoint of progression-free survival. Secondary endpoints of overall response rate and disease control rate (which includes complete and partial responses, plus stable disease ? 3 months duration) also did not show a statistically significant benefit. According to the prespecified analysis plan, the statistical significance of durable response - a secondary endpoint that measures the proportion of patients who achieved a complete or partial response that lasts ? 6 months - is too early to evaluate. The observed differences in progression-free survival, overall response, disease control and durable response all numerically favored the group that received Genasense®.

Overall survival - the other co-primary endpoint in AGENDA - is too early to evaluate, as prospectively specified. An analysis for futility, which was defined as ? 50% conditional power to observe a statistically significant benefit of Genasense under the prospectively assumed hazard ratio of 0.69, has been conducted for the co-primary endpoint of overall survival. AGENDA has passed this futility analysis. The prospectively specified analyses for both overall survival and durable response will be conducted when the data are mature. The safety profile of Genasense in AGENDA was consistent with prior studies.

Quantitative details of the today’s announced results will be presented at the international conference, “Molecular Targets and Cancer Therapeutics”, that will be held November 15-19, 2009 in Boston, MA. The AGENDA results will be featured in an oral session on Monday November 15, 2009 at 5:00 PM ET. The “Targets Meeting” is jointly sponsored by the American Association for Cancer Research (AACR), the U.S. National Cancer Institute (NCI), and the European Organization for Research and Treatment of Cancer (EORTC)

“At this time, we cannot predict whether more mature data will reveal a benefit in either overall survival or durable response,” said Dr. Raymond P. Warrell., Jr., Genta’s Chief Executive Officer. “However, the immediate failure to confirm a significant improvement in progression-free survival will preclude our submission of a regulatory application this year. Management and the Board are currently assessing the impact of these data on the Company’s strategic direction. The Company plans to provide further updates in the near future.

Genta is very grateful for the tireless dedication of our employees and for the contributions of the many physicians, patients, and families who have worked to advance Genasense for the treatment of melanoma.”

About AGENDA

AGENDA is a Phase 3, randomized, double-blind, placebo-controlled trial of dacarbazine administered with or without Genasense® in patients who have not previously received chemotherapy. AGENDA employs a biomarker to define those patients who derived maximum clinical benefit during the preceding study. These patients are characterized by low-normal levels of LDH (lactate dehydrogenase), a tumor-derived enzyme that is readily detected in blood.

Source
Genta

Celldex Therapeutics, Inc. (NASDAQ: CLDX) announced positive results from Phase 1 studies of CDX-1307 in patients with advanced epithelial pancreatic cancer. CDX-1307, the first candidate from the Company’s Precision Targeted Immunotherapy Platform, utilizes monoclonal antibodies to deliver vaccine directly to the patient’s immune system and focuses the immune system against hCG beta (hCG- ), a cancer-associated target believed to play a role in more aggressive forms of the disease. The data, presented at the 24th Annual Meeting of the International Society for Biological Therapy of Cancer (iSBTc) in Washington, D.C., demonstrated enhanced immunological and biological responses and support the planned initiation of Phase 2 clinical trials in hCG- expressing cancers.

The Phase 1 studies investigated the safety and immunogenicity of CDX-1307 alone and in combination with adjuvants, including GM-CSF and Toll-like Receptor (TLR) agonists (poly-ICLC or Hiltonol™ and R848 or resiquimod). The studies enrolled more than 80 patients with heavily pretreated, advanced-stage breast, colon, bladder and pancreatic cancer, with an average of 4.6 prior therapies across the treatment population. All patient cohorts demonstrated a favorable safety profile with no dose limiting toxicity to date. The combination of CDX-1307 with TLR agonists significantly enhanced immune responses against hCG- , providing strong humoral responses in 88% of patients and cellular immune responses in 57% of patients analyzed to date. Immune responses occurred even in the presence of high circulating levels of hCG- , suggesting that the CDX-1307 can overcome antigen tolerance in advanced and heavily pretreated cancers. Nine patients in the studies experienced disease stabilization from 2.3 months to 11.4 months following the initiation of CDX-1307 vaccination. Two of these patients have received multiple courses of CDX-1307 and continue treatment with stable disease at 6.4 and 11.4 months. These data provide the basis for advancing CDX-1307 into a front-line patient population selected for hCG- expressing cancers. Celldex is planning the initiation of a Phase 2 study in patients with newly diagnosed bladder cancer in the first quarter of 2010.

“We have developed a CDX-1307 combination regimen that has shown promising results eliciting immunogenic and biologic responses in patients with advanced, difficult to treat and heavily pretreated cancers,” said Thomas Davis, M.D., Senior Vice President and Chief Medical Officer of Celldex Therapeutics. “Based on these findings, we will focus our efforts on CDX-1307 in earlier stage cancers where hCG- appears to play an important role and where immunotherapy is likely to be even more effective, beginning with the initiation of a Phase 2 study in early-stage bladder cancer. Bladder cancer frequently expresses hCG- and represents a clear unmet medical need-which we believe provides an excellent opportunity for CDX-1307.”

About CDX-1307

CDX-1307 is in early-stage development for the treatment of epithelial cancers that express the beta chain of human chorionic gonadotropin, known as hCG- . hCG- is a tumor associated antigen that is often linked to more aggressive disease and poor patient outcome. CDX-1307 is a fusion protein composed of a mannose receptor-specific human monoclonal antibody genetically fused with the hCG- antigen. This antibody-vaccine is designed to deliver hCG- directly to the patient’s immune system via the antibody which attaches to dendritic cells and induce strong hCG- specific immune responses. This antibody delivery approach contrasts with earlier generation vaccines that required dendritic cells to find and ingest vaccines.

Source
Celldex Therapeutics, Inc.

Heart disease and stroke are the leading causes of death for women worldwide, killing more than 8.6 million, more than the total number who die from malaria combined.

However, the risk for women is largely under-estimated, by both the general population and often by the medical profession itself. This is due to the fact that women usually suffer from CVD 10 years later in their life than men: the risk increases after menopause, partly because of ovarian hormone deficiency that favours hypertension, obesity and the metabolic syndrome.

In the report presented at the conference (2), Professor Stramba Badiale, MD, PhD at the Department of Rehabilitation Medicine, IRCCS Istituto Auxologico Italiano, finds that women are underrepresented in cardiovascular research in Europe. “In the 62 randomized clinical trials published between 2006 and July 2009, only 33.5% of enrolled participants were women,” he says.

This underrepresentation is particularly noticeable in the fields of cholesterol-lowering therapy, ischaemic heart disease and heart failure.

Professor Roberto Ferrari, President of the ESC says: “With regard to cardiovascular health, we do lack data for women simply because the majority of clinical trials are conducted on men. It is important to have special clinical trials conducted only on women because their cardiovascular pathology is, at least at some point during their lives, different from that of men and it is incorrect to apply data derived from studies on men to women.”

Another finding of the report that supports the conference programme is that only 50% of the clinical trials conducted in the last three years which enrolled both men and women reported the analysis of the results by gender.

Susanne Logstrup, director of the EHN, regrets that, as a result, “safety and efficacy of several drugs have been evaluated predominantly in male populations.”

Professor Stramba-Badiale is hopeful that the report and the conference will encourage new practice amongst the research community, with a systematic enrolment of women in clinical trials. “New data should improve the clinical management of CVD and, in the future, develop possible gender specific diagnostic and therapeutic strategies,” he says.

The research is part of the EuroHeart project, which aims at defining areas of policies and public health interventions which can contribute to prevent avoidable deaths and disability across Europe. It is led by the European Society of Cardiology, in partnership with the European Heart Network, and is co-funded by the European Commission Public Health Programme 2003-2008.

The ‘Red alert for women’s hearts’ conference will systematically review the place of women in all aspects of scientific literature, whether clinical trials, guidelines, medical curriculum or regulatory processes.

More than 60 awareness campaigns addressing the particular issue of women and cardiovascular diseases have been organised in the last 20 years in the 19 countries participating in WP 6 of the EuroHeart project. This is evidence that national Heart Foundations and Cardiac Societies have long been aware of the urgent need to promote the issue amongst the female population and health professionals. The results of campaigns showed an increased awareness that cardiovascular diseases are the leading cause of death for women. Despite this, gender-specific training for cardiologists is still lacking in the majority of European countries.

The objective of this conference is to create a series of recommendations for policy makers, research funding agencies and regulatory entities, at both national and EU level.

Red Alert for Women’s Hearts is also the opportunity to look at how countries address the lack of information of the population and of health professionals, by giving an overview of past campaigns and their impact, country by country.

Notes:

1. EuroHeart involves partners in 21 countries in the EU and the EEA receives co-funding from the European Commission Public Health Programme 2003-2008.

2. Research published by the ESC and the EHN in the report: Red Alert for Women’s Hearts, Women and Cardiovascular Research in Europe (November 2009).

References: The European Society of Cardiology (ESC) represents more than 62,000 cardiology professionals across Europe and the Mediterranean. Its mission is to reduce the burden of cardiovascular disease in Europe.

Source: ESC Press Office

European Society of Cardiology