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Study Demonstrates OPKO’s 4Kscore Test Reduces Unnecessary Prostate Biopsies While Improving Risk Prediction for Aggressive Prostate Cancer

On February 9, 2016 OPKO Health, Inc. (NYSE: OPK) reported the results of a study for the 4Kscore Test’s clinical utility in reducing the number of prostate biopsies performed, while increasing the probability of detecting aggressive prostate cancer in men with abnormal prostate-specific antigen (PSA) levels and or digital rectal examination (DRE) results (Press release, Opko Health, FEB 9, 2016, View Source [SID:1234509014]). The peer-reviewed study, "The 4Kscore Test Reduces Prostate Biopsy Rates in Community and Academic Urology Practices", written by Badrinath Konety, MD, et al. and published in the January 2016 edition of Reviews in Urology, a MedReviews, LLC. Publication, which included 611 patients seen by 35 academic and community urologists across the United States, indicated that consideration of results from the 4Kscore tests led to 64.6% fewer prostate biopsies being performed among participating patients.

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"The 4Kscore test is a useful tool in identifying men with a significant risk of having an aggressive form of prostate cancer, who are most likely to benefit from a prostate biopsy and selective treatment or intensive intervention, while avoiding biopsies in men who are at low risk for developing aggressive disease," commented lead researcher Badrinath Konety, M.D., Dougherty Family Chair in Uro-Oncology and director of the Institute for Prostate and Urologic Cancers at the University of Minnesota. "Our findings suggest that PSA screening, when coupled with the 4Kscore test, can be made more specific, reduce biopsy complications and overtreatment, and be a more cost-effective solution for managing a patient’s prostate health."

Dr. Konety and colleagues evaluated the influence of the 4Kscore test on urologist-patient decisions about whether to perform a biopsy in men who had an abnormal PSA and or DRE result. Test results for patients were stratified into low risk ( < 7.5%), intermediate risk (7.5%-19.9%) and high risk (≥20%) for developing aggressive prostate cancer. Nearly half (49.3%) of the men were categorized as low risk; 25.7% and 25.0% fell into the intermediate-risk and high-risk categories, respectively. Notably, the 4Kscore test results influenced biopsy decisions in 88.7% of the men. In the three risk groups, a biopsy was avoided in 94.0%, 52.9%, and 19.0% of men in the low, intermediate, and high-risk categories, respectively.

A higher 4Kscore test result was significantly associated with a greater likelihood of having a prostate biopsy (P < 0.001). Among the 171 men who had a biopsy, 45 of the 104 cases (43.3%) with a high-risk 4Kscore test result (≥20% risk) were found to have aggressive prostate cancer upon prostate biopsy.

About the 4Kscore Test

The 4Kscore is the only blood test that accurately identifies an individual patient’s risk for aggressive prostate cancer, the lethal form of prostate cancer. The 4Kscore test uses a proprietary algorithm that incorporates the blood levels of four different prostate-derived kallikrein proteins: Total PSA, Free PSA, Intact PSA and Human Kallikrein-2 (hK2), plus the patient’s age, and other clinical information to calculate the percentage risk (probability) of finding a Gleason Score 7 or higher grade of prostate cancer. The four kallikrein panel of biomarkers utilized in the 4Kscore Test is based on over a decade of research conducted by scientists at Memorial Sloan-Kettering Cancer Center and leading European institutions and is included as a standard of care in the 2015 NCCN Prostate Cancer Early Detection Guidelines. The 4Kscore test provides individualized risk for the presence of aggressive prostate cancer and adds new information to the shared decision making discussion between the Urologist and the patient.

American Society of Clinical Oncology (ASCO) Clinical Practice Guideline Recommends Use of Prosigna (PAM50) for Guiding Treatment Decisions in Early Stage Breast Cancer Patients

On February 09, 2016 NanoString Technologies, Inc. (NASDAQ:NSTG), a provider of life science tools for translational research and molecular diagnostic products, reported that the updated American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Clinical Practice Guideline on the appropriate use of breast tumor biomarker assay results recommends the use of the Prosigna Breast Cancer Prognostic Gene Signature Assay (PAM50) to guide decisions on adjuvant systemic therapy for women with early-stage invasive breast cancer with known hormone receptor and HER2 status (Press release, NanoString Technologies, FEB 9, 2016, View Source [SID:1234509010]). The Prosigna assay was one of only two such assays to receive a "high" rating of evidence quality together with a "strong" recommendation.
"Prosigna’s inclusion in the ASCO (Free ASCO Whitepaper) Clinical Practice Guideline, specifically for use in guiding decisions on adjuvant systemic therapy for women with early stage breast cancer, places Prosigna on equal footing with the Oncotype DX test," said Brad Gray, President and Chief Executive Officer of NanoString Technologies. "This is the sixth major breast cancer treatment guideline to include Prosigna in the past twelve months, and it further strengthens our case for reimbursement and market adoption."

The ASCO (Free ASCO Whitepaper) Clinical Practice Guideline provides evidence-based recommendations based on a comprehensive review and analyses of the relevant literature for each recommendation. The Guideline states that if a patient has hormone receptor-positive, HER2-negative (node-negative) breast cancer, the clinician may use the PAM50 (Prosigna) risk of recurrence (ROR) score, known as the Prosigna Score in the United States, in conjunction with other clinicopathologic variables, to guide decisions on adjuvant systemic therapy.

"We applaud the rigorous scientific methodology and transparency that the ASCO (Free ASCO Whitepaper) multidisciplinary expert breast cancer panel applied in reviewing and weighing the available scientific evidence," said Alessandra Cesano, M.D., Ph.D., Chief Medical Officer of NanoString. "By focusing on the clinical utility of sparing women unnecessary chemotherapy, the Committee has helped future breast cancer patients avoid the risk of fatal, life-threatening, or permanently changing toxicities."

The Guideline, together with additional information including details of the methodology and review of the scientific literature, is available at: View Source

About the Prosigna Breast Cancer Prognostic Gene Signature Assay and nCounter Dx Analysis System
The Prosigna Assay provides a risk category and numerical score for assessment of the risk of distant recurrence of disease at 10 years in postmenopausal women with node-negative (Stage I or II) or node-positive (Stage II), hormone receptor-positive (HR+) breast cancer. Based on the PAM50 gene signature initially discovered by Charles Perou, Ph.D. and colleagues, the Prosigna Assay is an in vitro diagnostic tool that utilizes gene expression data weighted together with clinical variables to generate a risk category and numerical score to assess a patient’s risk of distant recurrence of disease. The Prosigna Assay measures gene expression levels of RNA extracted from formalin-fixed paraffin embedded (FFPE) breast tumor tissue previously diagnosed as invasive breast carcinoma.

The Prosigna Assay requires minimal hands-on time and runs on NanoString’s proprietary nCounter Dx Analysis System, which offers a reproducible and cost-effective way to profile many genes simultaneously with high sensitivity and precision.

The nCounter Dx Analysis System is a highly automated and easy-to-use platform that utilizes a novel digital barcoding chemistry to deliver high precision multiplexed assays. The system is available in the multi-mode FLEX configuration, which is designed to meet the needs of high-complexity clinical laboratories seeking a single platform with the flexibility to run the Prosigna Breast Cancer Assay and, when operated in the "Life Sciences" mode, process translational research experiments and multiplexed assays developed by the laboratory.

In the United States, the Prosigna Assay is available for diagnostic use when ordered by a physician. The Prosigna Assay has been CE-marked and is available for use by healthcare professionals in the European Union and other countries that recognize the CE Mark, as well as Canada, Israel, Australia, New Zealand and Hong Kong.

In the U.S., the Prosigna Assay is indicated in female breast cancer patients who have undergone surgery in conjunction with locoregional treatment consistent with standard of care, either as:
(1) a prognostic indicator for distant recurrence-free survival at 10 years in postmenopausal women with Hormone Receptor-Positive (HR+), lymph node-negative, Stage I or II breast cancer to be treated with adjuvant endocrine therapy alone, when used in conjunction with other clinicopathological factors or (2) a prognostic indicator for distant recurrence-free survival at 10 years in postmenopausal women with Hormone Receptor-Positive (HR+), lymph node-positive (1-3 nodes), Stage II breast cancer to be treated with adjuvant endocrine therapy alone, when used in conjunction with other clinicopathological factors. The device is not intended for patients with four or more positive nodes.

For more information, please visit www.prosigna.com.

U.S. Food and Drug Administration Grants Breakthrough Therapy Designation for Adaptimmune’s Affinity Enhanced T-cell Therapy Targeting NY-ESO in Synovial Sarcoma

On February 09, 2016 Adaptimmune Therapeutics plc (Nasdaq:ADAP), a leader in the use of TCR engineered T-cell therapy to treat cancer, reported that the U.S. Food and Drug Administration (FDA) has granted Breakthrough Therapy designation for the company’s affinity enhanced T-cell therapy targeting NY-ESO in synovial sarcoma for HLA-A*201, HLA-A*205 or HLA-A*206 allele-positive patients with inoperable or metastatic synovial sarcoma who have received prior chemotherapy and whose tumor expresses the NY-ESO-1 tumor antigen (Press release, Adaptimmune, FEB 9, 2016, View Source [SID:1234509349]).

"We are committed to investigating the potential of our NY-ESO-1-T cell therapy across a variety of cancers. We are pleased that the FDA has granted Breakthrough Therapy designation for our T-cell therapy in synovial sarcoma, recognizing both the unmet need for patients suffering from this disease as well as the promise of these early data," said Dr. Rafael Amado, Adaptimmune’s Chief Medical Officer. "We look forward to working closely with the FDA to expedite the clinical development of this therapeutic candidate."

The Breakthrough Therapy designation was based on the results of a phase I/II trial in patients with unresectable, metastatic or recurrent synovial sarcoma who have received prior chemotherapy. Patients were treated with lymphodepleting chemotherapy followed by immunotherapy with T-cells engineered to recognize an HLA-A2 restricted NY-ESO-1 peptide.

Data from this study were most recently presented at the 2015 Annual Meeting of the Society of Immunotherapy for Cancer (SITC) (Free SITC Whitepaper) in November 2015. In the primary efficacy analysis, 60 percent of the 10 patients receiving the target dose of cells responded, and there was a 50 percent overall response rate in the 12 patients receiving any dose of cells. 90 percent (9/10) of those patients who received the target dose and 75 percent (9/12) of all patients were alive and on long term follow-up. The most common adverse events included nausea, anemia, pyrexia, lymphopenia and neutropenia. Cytokine release syndrome (CRS) was seen in four of twelve subjects, with grade 3 CRS observed in two subjects; no grade 4 CRS events were observed.

Adaptimmune recently announced that it will aim to initiate pivotal studies with its affinity enhanced T-cell therapy targeting NY-ESO in synovial sarcoma around year end 2016, and that it will also explore development in myxoid round cell liposarcoma. Studies with this therapy are also under way in myeloma, melanoma, ovarian cancer and non-small cell lung cancer.

About Breakthrough Therapy Designation
The breakthrough therapy designation was enacted as part of the Food and Drug Administration Safety and Innovation Act of 2012 and is intended to expedite the development and review of drugs for serious or life-threatening conditions. The criteria for breakthrough therapy designation require preliminary clinical evidence that demonstrates the drug may have substantial improvement on at least one clinically significant endpoint over available therapy. According to the FDA, breakthrough therapy designation conveys all of the fast track program features, more intensive FDA guidance on an efficient drug development program, an organizational commitment involving senior managers, and eligibility for rolling review and priority review of the company’s Biologic License Application when submitted.

About Soft Tissue Sarcoma
Soft tissue sarcomas can develop from soft tissues like fat, muscle, nerves, fibrous tissues, blood vessels, or deep skin tissues. There are approximately 50 types of soft tissue sarcomas, including synovial sarcoma, a cancer of the connective tissue around joints. Soft tissue sarcomas can develop at almost any anatomic site, such as the extremities, trunk or thorax, abdomen and retroperitoneum, pelvis and the head and neck region. The more common soft tissue sarcomas originate from muscle, nerve tissue, fat or deep skin tissue. For a number of sarcomas, such as synovial sarcoma, the tissue origin is not well characterized. Surgical resection is the standard therapy for localized disease and radiation therapy (preoperative or postoperative) is added in selected cases. The American Cancer Society estimates 11,930 new soft tissue sarcoma diagnoses (6,610 cases in males and 5,320 cases in females) in the United States in 2015, representing approximately 2 percent of all cancers, and approximately 4,870 Americans (2,600 males and 2,270 females) are expected to die of soft tissue sarcomas.

CTI BioPharma Provides Update On Clinical Hold Of Investigational Agent Pacritinib And New Drug Application In U.S.

On February 9, 2016 CTI BioPharma Corp. (CTI BioPharma) (NASDAQ and MTA: CTIC) reported an update regarding the clinical studies being conducted under the Company’s Investigational New Drug ("IND") application for pacritinib (Press release, CTI BioPharma, FEB 9, 2016, View Source;p=RssLanding&cat=news&id=2137027 [SID:1234509021]).

Following the issuance of the Company’s February 8, 2016, press release describing the partial clinical hold issued by the U.S. Food and Drug Administration (FDA) regarding those clinical studies, the Company received an oral communication from the FDA followed by a letter notifying the Company that the Company’s IND for pacritinib has been placed on full clinical hold. The Company has withdrawn its New Drug Application (NDA) until the Company has had a chance to review the safety and efficacy data from the PERSIST-2 Phase 3 clinical trial and decide next steps.

The FDA’s February 8, 2016, letter notes the interim overall survival results from PERSIST-2 show a detrimental effect on survival consistent with the results from PERSIST-1. The deaths in PERSIST-2 in pacritinib-treated patients include intracranial hemorrhage, cardiac failure and cardiac arrest. The FDA made recommendations that supersede the recommendations made by the FDA in connection with the partial clinical hold imposed by the FDA on February 4, 2016. The current recommendations include conducting dose exploration studies for pacritinib in patients with myelofibrosis, submitting final study reports and datasets for PERSIST-1 and PERSIST-2, providing certain notifications, revising relevant statements in the related Investigator’s Brochure and informed consent documents and making certain modifications to protocols. In addition, the FDA recommended that the Company request a meeting prior to submitting a response to full clinical hold.

Under the full clinical hold, all patients currently on pacritinib must discontinue pacritinib immediately and no patients can be enrolled or start pacritinib as initial or crossover treatment.

All clinical investigators worldwide have been delivered a notice of the full clinical hold.

Nymox Announces Prostate Cancer Clinical Trial Results From Completed 18 Month Endpoint Study

On February 09, 2016 Nymox Pharmaceutical Corporation (NASDAQ:NYMX) reported results from the completion of the Company’s U.S. 40 month (18 month outcomes) localized prostate cancer Phase 2 NX03-0040 clinical trial of fexapotide triflutate (NX-1207) (Press release, Nymox, FEB 9, 2016, View Source [SID:1234509016]). The study successfully met its pre-determined endpoints. Cancer progression clinical outcomes were significantly improved in the fexapotide treated patient groups.

The clinical trial commenced in February 2012 at 28 U.S. investigational clinical trial sites and enrolled 147 patients with low grade localized (T1c) prostate cancer. The study lasted 40 months overall from the first patient randomized to the last patient 18 month endpoints.

Results from the completed 18 month outcome study after a single injection of fexapotide included the following:

Absence of tumors (Primary Endpoint) controlled for size in baseline area: fexapotide 15 mg superior to control (p=.035); crossover fexapotide 15 mg superior to control (p=.002); crossover fexapotide overall superior to control (p=.014).

75.5% reduction in biopsy proven prostate cancer Gleason upgrades (pathological progression) after 18 months in fexapotide 15 mg treated patients compared to control (p=.0055). 71.7% reduction in prostate cancer Gleason upgrades in fexapotide treated patients overall (p=.0045 vs controls).

84.8% reduction after 18 months in surgery or radiotherapy instituted for prostate cancer Gleason upgrade (biopsy worsening) in fexapotide treated patients overall compared to control group (p=.014).

54.8% reduction after 18 months in surgery or radiotherapy instituted for all causes with or without prostate cancer Gleason upgrade in fexapotide 15 mg treated patients compared to control (p=.026).

Significant improvement for fexapotide patients compared to controls in 4 out of 4 Secondary Endpoints. Tumor volume reduction in the treated area, combined dosages (p=.04); tumor volume change in prostate overall, fexapotide patients overall (p=.014); median tumor grade outcome in the treated area, all dosages (fexapotide median benign, vs control median Gleason 3+3), and superior median tumor grade in prostate overall, fexapotide 15 mg vs controls.

Consistent safety results with no significant drug-related adverse events and no significant related sexual adverse events.

Overall superior results for the fexapotide 15 mg dose compared to the 2.5 mg dose (dose-response).

Other statistically significant improvement outcomes in fexapotide patients compared to controls, to be presented comprehensively at medical meetings.
"These results demonstrate that a single targeted office injection of fexapotide has led to statistically significant improvement in outcomes with much less surgery or radiotherapy required after 18 months. This means a reduction in patient discomfort, and a reduction in permanent side effects and life changes when the more invasive treatments are required," said Paul Averback, CEO of Nymox.

Dr. Averback added, "Based on these outcomes, we believe there are exciting potential patient benefits from one or more painless fexapotide office injections for this common and distressing condition."

The Company will report at a later date concerning its plans for moving the compound forward toward the market for this important medical problem.