“Unprecedented Sensitivity and Specificity” in Ovarian Cancer
News Jan 29, 2015
ANGLE plc has announced that the Medical University of Vienna, one of its key opinion leaders, has reported highly convincing patient data in support of the use of ANGLE’s Parsortix system in the detection of ovarian cancer.
The Medical University of Vienna will now lead, in collaboration with ANGLE, a clinical study of the use of the Parsortix system as a clinical application in the routine detection and treatment of ovarian cancer patients.
The multi-centre clinical study will be in collaboration with other members of the European Network for Translational Research in Ovarian Cancer (EUTROC) and the Tumour bank Ovarian Cancer Network (TOC) from Austria, Belgium, Germany and UK. It is expected to take 18 months to complete.
Assuming the clinical study confirms the recent patient study results then ANGLE will be able to make clinical sales of the Parsortix system to help inform detection of ovarian cancer and clinical decision-making in its treatment.
The patient study was undertaken under ANGLE’s collaboration agreement with the Ludwig Boltzmann Cluster ‘Translational Oncology’ led by the head of the interdisciplinary Molecular Oncology Group at the Medical University of Vienna, Professor Robert Zeillinger. The study utilized RNA markers developed in Vienna to analyze the cells harvested by ANGLE’s Parsortix system.
The Vienna team has worked for many years with a wide range of CTC systems, both those commercially available from ANGLE’s competitors and new technologies under development including commercial and academic systems. Due to lack of suitable cell surface markers, antibody-based systems are ineffective for ovarian cancer.
The best result that has been obtained to date with other non-antibody based systems is a CTC detection sensitivity level of 24.5% (i.e. capturing CTCs from only one quarter of ovarian cancer patients).
Against this context, Dr Eva Obermayr, Principal Investigator at the Medical University of Vienna describes the results with ANGLE’s Parsortix system as “sensational” and offering “unprecedented sensitivity and specificity”. The results indicated a sensitivity of 90% for primary epithelial ovarian cancer at a specificity of 100%. Epithelial ovarian cancer (also known as ovarian carcinoma) is the most common ovarian cancer and accounts for some 90% of cases.
If these results are repeated in a prospective clinical study, Professor Zeillinger believes that ANGLE’s Parsortix system together with the proprietary RNA marker panel could be adopted in clinical practice to help inform clinical decision-making for ovarian cancer patients in:
• Detection of cancer in high risk or genetically pre-disposed patients (detection)
• Monitoring therapy and selection of therapies in treatment of ovarian cancer patients (therapy monitoring)
• Monitoring of ovarian cancer patients in remission for early detection of relapse (remission monitoring)
ANGLE estimates that the ovarian cancer sales potential available for the Parsortix system in the European and United States markets would be in excess of £300 million per annum.
Annually 239,000 women are diagnosed with ovarian cancer worldwide. There is a high mortality rate and 152,000 die from it each year. Ovarian cancer is commonly known as the silent killer due to its lack of symptoms in its earlier stages. It is frequently diagnosed late in which case the UK five year survival rate is only 3.5% for Stage IV and 18.6% for Stage III at diagnosis (Source: Cancer Research UK Ovarian Cancer survival statistics). In contrast where it is diagnosed at Stage I, the UK five year survival rates are much higher at 90%. As a result there is an acute medical need for improved ovarian cancer detection.
Ovarian cancer surgery is highly complex and maximal tumour removal has a very strong impact on survival. Women with the diagnosis or a strong indication of ovarian cancer can be referred for surgery to specialists in gynaecologic oncology. The consequence is a significantly better outcome compared to the situation when surgery is performed by a general gynaecologist and cancer is diagnosed at this point. There would therefore be great clinical benefit if it were possible to know in advance of surgery if an abnormal pelvic mass is malignant.
A common approach is to use a blood test for the biomarker CA-125 for detection of epithelial ovarian cancer, either alone or in combination with another marker HE4. However the quoted sensitivity for CA-125 is only 63% (i.e. 37% of cancers are missed as false negatives) and as a result it is not considered effective.
Vermillion, a US Nasdaq listed company, has developed OVA1, an alternative epithelial ovarian cancer test that integrates biomarker measurement in blood and a software algorithm, which is FDA authorized and the company is now beginning to commercialize. The Medicare reimbursement level for OVA1 is $516. The company estimate that, in the United States alone, there are some 200,000 patients with abnormal pelvic masses where surgery is undertaken, which may be investigated with OVA1 (of which 22,000 will have ovarian cancer) suggesting a United States market for a specific segment of the larger detection market of in excess of $100m per annum. There is a substantially larger patient population in the United States of some 750,000 per annum if all abnormal pelvic masses are investigated. Vermillion quotes a sensitivity of 93% and specificity of 43% for OVA1 and indicates that this is a considerable improvement over CA-125.
If the clinical study confirms the patient data then ANGLE’s Parsortix system has the potential to substantially out-perform the current standard of care in ovarian cancer, particularly in relation to specificity (i.e. if a person does not have the disease how often will the test be negative).
The group at the Medical University of Vienna believes that the exceptionally good results with the Parsortix system are explained by the high purity of the Parsortix harvest (very low numbers of leukocytes) combined with the sensitivity of their RNA markers.
Professor Robert Zeillinger, Head of the Molecular Oncology Group at the Medical University of Vienna, commented: “Using ANGLE’s Parsortix system with a panel of ovarian carcinoma-specific RNA markers, we were able to detect and analyze CTCs in 90% of patient samples at a specificity of 100%. This is an unprecedented test performance and we will be immediately moving to a clinical study to validate the use of this system in the detection and treatment of ovarian cancer patients. We will also be preparing a high impact publication on these results for discussion with our colleagues in ovarian cancer worldwide.”
ANGLE Founder and Chief Executive, Andrew Newland, commented: “These are highly encouraging results for the use of the Parsortix system. There is a very strong medical need in ovarian cancer for earlier detection and monitoring of patients and we hope our Parsortix system will be able to really make a difference. Commercially ovarian cancer is a substantial but tightly defined market where there is little competition. It is an ideal first clinical market for ANGLE to progress. We will be focusing our resources to deliver this opportunity as quickly as possible. Today’s announcement marks the start of ANGLE moving into the clinical phase.”