On March 14, 2016 Janssen-Cilag International NV reported that data from a post-hoc analysis of the Phase 3 COU-AA-302 trial showed that ZYTIGA (abiraterone acetate) plus prednisone provided an 11.8 months overall survival (OS) benefit (53.6 months vs 41.8 months; HR = 0.61 [95% CI, 0.43-0.87]; p = 0.0055), compared to an active control of placebo plus prednisone, in men with early and less aggressive chemotherapy-naïve metastatic castration-resistant prostate cancer (mCRPC) (Press release, Johnson & Johnson, MAR 14, 2016, View Source [SID:1234509557]).1

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Data from the post-hoc analysis, presented today at the European Association of Urology (EAU) 2016 Congress in Munich, Germany, demonstrated almost triple the OS benefit previously shown (4.4 months) in the final analysis of the COU-AA-302 trial (34.7 months ZYTIGA plus prednisone vs 30.3 months placebo plus prednisone; HR = 0.81 [95% CI, 0.70-0.93]; p = 0.0033). The final analysis was originally presented at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) 2014 Congress and included a broader range of men with asymptomatic or mildly symptomatic chemotherapy-naïve mCRPC.2

The post-hoc analysis divided patients into two groups to identify which group experienced a greater treatment benefit. The patients in Group 1 were in an earlier, less advanced and less symptomatic stage of the disease (which was defined as having a Brief Pain Inventory [BPI] Short Form score of 0-1, prostate-specific antigen [PSA] below 80 ng/ml and a Gleason score [GS] of below 8). Those in Group 2 were in a later, more advanced and more symptomatic stage of the disease (defined as a having a BPI of 2 or over and/or PSA of 80 ng/ml or above, and/or a GS of 8 or more). The analysis revealed that patients in both groups experienced an OS benefit when treated with ZYTIGA plus prednisone, compared to placebo plus prednisone (Group 1: 11.8 months; HR = 0.61 [95% CI, 0.43-0.87]; p = 0.0055) (Group 2: 2.8 months; HR = 0.84 [95% CI, 0.72-0.99]; p = 0.0321).1

"Post-hoc analyses such as this are very important in helping us to identify the patients who could benefit most from therapies such as novel hormone agents, and at what stage of a patient’s disease they could be most effective." said Professor Kurt Miller, Department of Urology, Chariteì Berlin, Berlin, Germany. "As men with prostate cancer are living longer, quality of life is an increasingly important factor for them and their families. It is therefore encouraging to see that when used earlier, patients can stay on ZYTIGA for longer and delay the need for additional, more invasive treatments," he continued.

In addition to OS benefit, the post-hoc analysis data also revealed that both groups showed improvement in disease progression, cancer-related pain and treatment duration when treated with ZYTIGA plus prednisone, compared to placebo plus prednisone:

Time to chemotherapy use was increased by 12.7 months in Group 1 and 8.8 months in Group 2
Group 1: 37.0 months vs 24.3 months; HR = 0.64 [95% CI, 0.46-0.89]; p = 0.0073
Group 2: 23.3 months vs 14.5 months; HR = 0.71 [95% CI, 0.60-0.85]; p = 0.0001

There was an improvement in median time to opiate use for cancer-related pain in both groups
Group 1: not reached vs 41.0 months; HR = 0.69 [95% CI, 0.48-0.99]; p = 0.0409
Group 2: 30.5 months vs 19.3 months; HR = 0.70 [95% CI, 0.59-0.84]; p = 0.0001

Median time on treatment almost doubled in both groups
Group 1: 20.4 months vs 11.2 months; HR = 0.41 [95% CI, 0.31-0.54]; p < 0.0001
Group 2: 12.3 months vs 7.2 months; HR = 0.54 [95% CI, 0.46-0.62]; p < 0.0001

Jane Griffiths, Company Group Chairman, Janssen Europe, the Middle East and Africa (EMEA) said: "Janssen is proud that this study continues to deliver valuable insights as to how best to treat different stages of advanced prostate cancer. We hope that this additional analysis will help healthcare professionals to define the most effective treatment pathway for individual patients. We remain committed to continuing our research in this area with the aim of helping to improve outcomes for men affected by this disease now and in the future."

-ENDS-
NOTES TO EDITORS

About the COU-AA-302 study

COU-AA-302 is an international, randomised, double-blind, placebo controlled Phase 3 study that included 1,088 men with mCRPC who had not received prior chemotherapy and were randomised to receive ZYTIGA (abiraterone acetate) 1,000 milligrams (mg) administered orally once-daily plus prednisone 5 mg administered twice-daily or placebo plus prednisone 5 mg administered twice-daily. The co-primary endpoints of the study were rPFS and OS. Key secondary endpoints included time to opiate use, time to initiation of chemotherapy, time to Eastern Cooperative Oncology Group (ECOG) performance status deterioration and time to PSA progression. The final analysis was presented at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) 2014 Congress.

The post-hoc analysis used the final dataset for the intent-to-treat population (n = 1088), to stratify patients into Group 1 (BPI 0-1, PSA < 80 ng/ml and GS < 8) and Group 2 (BPI = 2 and/or PSA = 80 ng/ml and/or GS = 8). OS, radiographic progression-free survival (rPFS), time to CT use, time to opiate use, and time on treatment with ZYTIGA plus prednisone vs placebo plus prednisone were analysed by the Kaplan–Meier method and Cox proportional hazards regression.

About ZYTIGA (abiraterone acetate)

ZYTIGA is the only approved therapy that inhibits production of androgen, which fuels prostate cancer growth, via inhibiting the CYP17 enzyme complex present at three sources: the testes, adrenals and the tumour itself.

ZYTIGA has been approved in more than 90 countries and to date, has been prescribed to more than 269,500 men worldwide.

Indication3

In 2011, ZYTIGA in combination with prednisone/prednisolone was approved by the European Commission (EC) for the treatment of metastatic castration-resistant prostate cancer (mCRPC) in adult men whose disease has progressed on or after a docetaxel-based chemotherapy regimen.

In December 2012, the EC granted an extension of the indication for ZYTIGA permitting its use, in combination with prednisone or prednisolone, for the treatment of mCRPC, in adult men who are asymptomatic or mildly symptomatic after failure of androgen deprivation therapy in whom chemotherapy is not yet clinically indicated.3

Further Information3

For a full list of side effects and for further information on dosage and administration, contraindications and other precautions when using ZYTIGA, please refer to the summary of product characteristics, which is available at: View Source;mid=WC0b01ac058001d124

On March 14, 2016 SRI International reported that it has been awarded a contract worth up to US$19.8m from the National Cancer Institute (NCI) in the US to support the development of potential preventative cancer agents or vaccines (Press release, SRI International, MAR 14, 2016, View Source [SID:1234509560]).

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Under the three-year contract, which is part of the PREVENT Cancer Preclinical Drug Development Programme, the Menlo Park, CA-based firm’s SRI Biosciences will conduct preclinical studies to assess the efficacy of specific compounds or vaccines for preventing invasive-cancer development.

Researchers will also identify biomarkers to help quantify the effectiveness of the experimental compounds and vaccines.

The PREVENT Cancer Drug Development Program is an NCI-supported pipeline to bring new cancer preventing interventions and biomarkers through preclinical development towards clinical trials.

‘The discovery and development of cancer preventative agents is an area that is underserved, primarily because the length of required clinical trials can be resource-prohibitive for many companies. Our work in biomarker discovery may provide validated surrogate endpoints that can help to shorten clinical trials in cancer prevention,’ said Lidia Sambucetti, Senior Director of Cancer Biology, Centre for Discovery Technologies, SRI Biosciences, and principal investigator for the NCI contract. ‘The PREVENT programme is an opportunity to identify and advance novel strategies for cancer prevention.’

Under the PREVENT programme, for efficacy and biomarker testing, two NCI task orders in the area of cancer prevention have already been awarded to SRI Biosciences: the first to develop a mesothelin-based vaccine against ovarian cancer, and another to develop novel models for testing preventative agents against ovarian cancer.

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For the ovarian cancer programme, SRI Biosciences optimised a vaccine strategy designed to mount both antibody-based and cellular immunity against mesothelin tumour antigen. SRI researchers are currently testing whether the vaccine can help prevent ovarian cancer. In addition, SRI generated encouraging data supporting the development of a new model that will be used to test experimental drugs for ovarian cancer prevention.

On March 14, 2016 Celator Pharmaceuticals, Inc. (Nasdaq: CPXX) reported positive results from the Phase 3 trial of VYXEOS (cytarabine: daunorubicin) Liposome for Injection (also known as CPX-351) in patients with high-risk (secondary) acute myeloid leukemia (AML) compared to the standard of care regimen of cytarabine and daunorubicin known as 7+3 (Press release, Celator Pharmaceuticals, MAR 14, 2016, View Source [SID:1234509534]). The trial met its primary endpoint demonstrating a statistically significant improvement in overall survival. Data will be submitted for presentation at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) 2016 Annual Meeting.

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The median overall survival for patients treated with VYXEOS in the study was 9.56 months compared to 5.95 months for patients receiving 7+3, representing a 3.61 month improvement in favor of VYXEOS. The hazard ratio (HR) was 0.69 (p=0.005) which represents a 31 percent reduction in the risk of death versus 7+3. The percentage of patients alive 12 months after randomization was 41.5% on the VYXEOS arm compared to 27.6% on the 7+3 arm. The percentage of patients alive 24 months after randomization was 31.1% on the VYXEOS arm compared to 12.3% on the 7+3 arm.

"The overall survival advantage seen with CPX-351 compared to 7+3, along with a superior response rate and no increase in serious toxicity indicates that we’ll likely have a new standard of care for treating older patients with secondary AML," said Jeffrey E. Lancet, M.D., senior member and chief of the Leukemia/Myelodysplasia Program at Moffitt Cancer Center and the principal investigator for the study. "This represents a major step forward for a very difficult-to-treat patient population."

VYXEOS also demonstrated a statistically significant improvement in induction response rate (CR+CRi of 47.7% versus 33.3%; p=0.016) and this significance was maintained for the analysis of CR alone (CR of 37.3% versus 25.6%, p=0.040).

Sixty-day all-cause mortality was 13.7% versus 21.2%, in favor of patients treated with VYXEOS.

No substantial difference in Grade 3 or higher adverse events was observed between VYXEOS and 7+3. In the intent-to-treat population, Grade 3 or higher, hematologic adverse events were similar for overall infections, febrile neutropenia, and bleeding events. In the intent-to-treat population, Grade 3 or higher, non-hematologic adverse events were similar across all organ systems, including cardiac, gastrointestinal, general systems, metabolic disorders, musculoskeletal, nervous system, respiratory, skin and renal.

"These findings confirm that VYXEOS provides the first opportunity we’ve had in decades to extend survival for patients with high-risk AML," added Gail Roboz, M.D., Professor of Medicine and Director of the Leukemia Program at the Weill Medical College of Cornell University and the New York-Presbyterian Hospital in New York. "Also, more patients in remission means more who are eligible for potentially curative therapy."

Based on these results the company expects to submit a New Drug Application (NDA) for VYXEOS with the U.S. Food and Drug Administration (FDA) later this year and submit a Marketing Authorization Application (MAA) with the European Medicines Agency (EMA) in the first quarter of 2017.

"The successful outcome of this Phase 3 trial represents an important advance for AML patients, their families and clinicians," said Scott Jackson, Chief Executive Officer of Celator Pharmaceuticals. "It also marks a major milestone for Celator, for VYXEOS, and for our CombiPlex platform. We offer our sincere thanks to the patients and investigators who participated in this study and we will work closely with regulatory authorities to make this new treatment available to the AML community as soon as possible."

The clinical trial was conducted in partnership with The Leukemia & Lymphoma Society (LLS) through its Therapy Acceleration Program (TAP), which has supported the clinical development of VYXEOS beginning in Phase 2.

About VYXEOS

VYXEOS (cytarabine:daunorubicin) Liposome for Injection, also known as CPX-351, is a nano-scale co-formulation of cytarabine and daunorubicin at a synergistic 5:1 molar ration. VYXEOS represents a novel approach to developing combinations of drugs in which molar ratios of two drugs with synergistic anti-tumor activity are encapsulated in a nano-scale liposome in order to maintain the desired ratio following administration. VYXEOS was granted orphan drug status by the FDA and the European Commission for the treatment of acute myeloid leukemia (AML). VYXEOS was also granted Fast Track designation for the treatment of elderly patients with secondary AML. In addition to the Phase 3 trial, Celator published results from two randomized, controlled, Phase 2 trials with VYXEOS. The first trial was conducted in newly diagnosed elderly AML patients and the second trial was conducted in patients with AML in first relapse.

Phase 3 Trial Design

The randomized, controlled, Phase 3 trial (Protocol NCT01696084), enrolled 309 patients at 39 sites in the United States and Canada, and compared VYXEOS to the conventional cytarabine and daunorubicin treatment regimen (commonly referred to as 7+3) as first-line therapy in older (60-75 years of age) patients with high-risk (secondary) AML. Patients were stratified for age (60 to 69 and 70 to 75 years of age) and AML type; treatment-related AML, AML with documented history of MDS with prior treatment with hypomethylating agent therapy, AML with documented history of MDS without prior hypomethlyating agent therapy, AML with a documented history of chronic myelomonocytic leukemia (CMMoL), and de novo AML with a karyotype characteristic of myelodysplastic syndrome (MDS).

Patients were randomized 1:1 to receive either VYXEOS or 7+3. Patients could receive one or two inductions, and responding patients could receive one or two consolidations. First induction for VYXEOS was 100u/m2; days 1, 3, and 5 by 90-minute infusion and for the control arm was cytarabine 100mg/m2/day by continuous infusion for 7 days and daunorubicin 60mg/m2 on days 1, 2, and 3 (7+3). Second induction for VYXEOS-treated patients was 100u/m2 on days 1 and 3 and the control arm was cytarabine 100mg/m2/day by continuous infusion for 5 days and daunorubicin 60mg/m2 on days 1 and 2 (5+2).

Only patients with documented CR or CRi were eligible to receive chemotherapy consolidation. Consolidation for VYXEOS-treated patients was 65u/m2 on days 1 and 3 and the control arm was cytarabine 100mg/m2/day by continuous infusion for 5 days and daunorubicin 60mg/m2 on days 1 and 2 (5+2).

About AML

Acute myeloid leukemia (AML) is a rapidly progressing cancer of the blood characterized by the uncontrolled proliferation of immature blast cells in the bone marrow. AML is generally a disease of older adults, and the median age of a patient diagnosed with AML is about 67 years. The American Cancer Society estimates that there will be 19,950 new cases of AML and 10,430 deaths from AML in the U.S. in 2016. In Europe the number of new cases is estimated to be 18,000 and in Japan the number is 5,500. The Company estimates that nearly 70 percent of AML patients are over the age of 60, and approximately 75 percent are intermediate or high risk. Furthermore, approximately half of those patients are considered suitable for intensive treatment.

Even with current treatment, overall survival for AML is poor. In patients over 60 years of age, the 5 year survival rate is less than 10%. In high-risk (secondary) AML, overall survival is lower, resulting in an acute need for new treatment options for these patients.

On March 14, 2016 WEST LAFAYETTE, Ind. A company from the Purdue Startup Class of 2014 whose innovation could help researchers and oncologists see faster than ever which drug therapies will benefit cancer patients and to what extent, reported that it has received funding from the National Institutes of Health (Press release, Purdue Research Foundation, MAR 14, 2016, View Source [SID:1234509561]).

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KinaSense has received a one-year SBIR Phase l grant from the National Cancer Institute worth $203,120, with $50,000 in matching funds from the Indiana Economic Development Corporation and Elevate Ventures. The company’s technology is based on Purdue University intellectual property.

KinaSense’s technology measures the effects of cancer drugs that inhibit growth signals from a kinase, an enzyme in a cancer cell that causes the cell to grow. The technology takes information about what a particular kinase looks for in a substrate, or the protein it acts upon. It narrows the information to a shortlist of traits, which are used to design a molecular probe that reports whether or not the drug is blocking the target kinase’s action inside of the cell.

Steve Ouellette, co-founder and chief technology officer at KinaSense, said the grant will help the company begin laboratory operations.

"The SBIR funds allow us to begin working toward developing prototype tests that can be used in pre-clinical drug discovery to identify new treatments for cancer patients. Specifically, the tests we develop will be used to characterize inhibitors for a class of drug targets called receptor tyrosine kinases," he said. "The grant will also allow us benefits like having access to special programs offered by the NIH/NCI, such as I-Corps, which will help KinaSense mature as a company through specialized business development training."

Ouellette said the award is a major validation of the company’s vision and its technology.

"A lot of uncertainty was endured over the past year and a half developing research strategy, gathering support for the project from potential partners and performing due diligence on our business model," he said. "This grant is a rewarding culmination of that effort, and one of many major milestones toward realizing KinaSense’s mission to help save lives in the battle against cancer.

"I am infinitely grateful to all those who have assisted, especially the Purdue Foundry, our scientific advisers, Laurie Parker and Andrew Lipchik, and our early supporters, Horizon BioAdvance and the Elevate Purdue Foundry Fund."

Ouellette worked on the technology as a doctoral student when it was developed by Andrew Lipchik in the laboratory of Laurie L. Parker, then an assistant professor in Purdue’s College of Pharmacy. Parker and Lipchik co-founded KinaSense with Ouellette, and serve on its scientific advisory board.

About KinaSense

KinaSense is an early-stage biotechnology company based in West Lafayette, Indiana. Our mission is to help save lives in the battle against cancer. We develop novel tests for identifying new therapies and directing their use in the clinic. In doing so, we strive to be on the forefront of precision medicine for personalized cancer care.

On March 14, 2016 ProNAi Therapeutics, Inc. (NASDAQ: DNAI), a clinical-stage oncology company advancing novel therapeutics for patients with cancer and hematological diseases, reported that its oncology drug candidate PNT2258 has been granted Orphan Drug Designation by the U.S. Food and Drug Administration (FDA) for the treatment of diffuse large B-cell lymphoma (DLBCL) (Press release, ProNAi Therapeutics, MAR 14, 2016, View Source [SID:1234509844]). This is the second orphan drug designation obtained by ProNAi for PNT2258 for the treatment of DLBCL, following a similar grant by the European Commission in August 2015.

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"Achieving this regulatory milestone for PNT2258 is an important advancement in our registration-oriented development plan for this cancer drug in DLBCL, a disease for which there are limited treatment options, particularly in patients who relapse or do not respond to front-line therapies." said Dr. Nick Glover, President and CEO of ProNAi.

Orphan drug designation is typically granted for novel drugs or biologics that are intended to treat rare medical diseases or conditions that affect less than 200,000 people in the United States. The designation qualifies the sponsor for certain incentives including seven years of market exclusivity after a drug’s approval, tax credits for clinical research costs, and certain application fee waivers.

ProNAi has also previously received European Commission Orphan Drug Designation for PNT2258 for the treatment of patients with DLBCL. In addition to a 10-year period of market exclusivity in the EU following marketing authorization, receiving orphan drug designation provides other incentives for companies, including scientific advice and protocol assistance during the product’s development phase.

About PNT2258 and DLBCL
ProNAi is actively enrolling patients in "Wolverine", a Phase 2 trial evaluating PNT2258 for the treatment of relapsed or refractory DLBCL and in "Brighton", a Phase 2 trial evaluating PNT2258 for the treatment of Richter’s transformation.

PNT2258 is designed to target cancers that overexpress BCL2, an important and validated oncogene known to be dysregulated in many types of cancer. BCL2 overexpression is thought to be a key driver of DLBCL, an aggressive form of cancer that is the most prevalent form of Non-Hodgkin lymphoma (NHL), comprising approximately 30% of the annual NHL diagnoses in the United States according to the Leukemia & Lymphoma Society (2013).

DLBCL affects mostly middle aged and older adults and is aggressive but potentially curable. First-line treatment of intensive combination chemotherapy involving rituximab may cure approximately 67% of patients. If this fails, second-line treatment is typically platinum-based chemotherapy along with continued rituximab. In the event that a response is achieved with second-line treatment, patients may be given a hematopoietic stem cell transplant. If second-line treatment or the transplant fails, patients are left with few options and little hope of a curative therapy. The median survival for third-line DLBCL patients is less than a year.