AppyScore™
AppyScore™ is a one-of-a-kind appendicitis triage blood screening test for patients entering an Emergency Room/Urgent Care facility complaining of abdominal pain. This new rapid blood testing system has the potential to greatly increase speed and accuracy of diagnosis, reduce the high levels of radiation exposure associated with CT scanning, improve both the standard of care and patient outcomes, while saving the U.S. health care system billions of dollars annually. In November of 2007 we received our Pre-IDE response from the FDA and, throughout 2008 we have been working to complete the required clinical and non-clinical studies to secure a 510(k) (Pre-Market Notification) regulatory clearance which we believe we will submit to the FDA before the end of 2008. We anticipate entering into an agreement with a worldwide marketing partner prior to product launch.
The AppyScore test is a blood-based specialized assay test designed to detect a marker in the blood associated with appendicitis. The marker demonstrates a linear (or direct) correlation to the histopathologic severity of appendicitis. When a patient enters the emergency room with abdominal pain, many factors are evaluated. Most physicians will order routine laboratory work including full blood chemistry, complete white blood cell count and a urine analysis. While waiting for these results the ER physician will typically obtain the patient’s history and perform a complete physical exam. To gain an initial clinical impression the ER physician will then typically combine these physical findings with the results of the specific blood and urine analysis lab tests. At this point, if concerned about appendicitis they will typically then order a CT scan and/or in more rare situations an ultrasound. Unfortunately, it is often hard to visualize the appendix using either such imaging methodology, and some studies report it is impossible to make an accurate diagnosis based upon imaging up to 40% of the time. Frequently, if the physician is unsure of the diagnosis and the patient is male, the patient will be sent to surgery for an appendectomy. If the patient is female and passes a gynecological exam, she will then be sent to surgery for an appendectomy. The current standard of care for appendicitis in the US, which is heavily dependent on abdominal CT scanning typically results in 1 in 7 patients having a normal appendix removed due to inaccurate diagnosis. We expect our AppyScore test will take under 45 minutes and should easily be incorporated within initial routine laboratory work in the emergency room. Our test will provide the only non-subjective, numerical value approach to assist physicians in their diagnostic workup or rule-out of appendicitis and provide important new information as doctors form their initial clinical impression in a given patient with abdominal pain. By way of comparison, using a CT scan as the primary screen test typically takes 3-5 hours or longer to obtain results in a hospital setting and is a subjective evaluation as compared to AppyScore.
In late December 2007, we outlined plans for submitting our final data package to the FDA for market approval of AppyScore. This followed the official pre-IDE response from the FDA in November 2007, and we plan to file our submission to receive FDA 510(k) clearance, which will involve a large clinical study estimated at 800 patients in multiple hospital sites, prior to the end of 2008. (Subject to levels of patient recruitment.) Typically a 510(k) review is completed within 90 days of submission, however this process can be extended in the event the FDA has questions or requires additional information. We are currently proceeding under supervision of the Company’s FDA consultants to complete work in the following primary areas for our AppyScore™ ELISA test:
- Completion of the FDA 510(k) Clinical section via our clinical trial, which is currently underway.
- Completion of the FDA 510(k) Non-clinical section, which is in the final stages of completion.
- Preparation of FDA 510(k) Final-submission package for clearance by FDA.
In order to receive FDA 510(k) clearance, we must successfully demonstrate the performance characteristics of the final GMP-validated device. This includes non-clinical laboratory performance testing, like assay precision and analytical sensitivity, as well as clinical testing in the field. We have selected a manufacturer for the AppyScore screen test with extensive experience in manufacturing in-vitro diagnostic devices according to Code of Federal Regulations 21 CFR 820, and which has been registered with the FDA to manufacture these types of devices.
In September 2007, we announced the results of a 471 patient study conducted at multiple hospital sites under appropriate Institutional Review Board Approvals and patient consent. Out of 471 patients, 100 were normal presumably healthy control donors. The 100 normal AppyScore control individuals were used to characterize and confirm the blood level of the proprietary biomarker used in AppyScore in normal healthy individuals. The remaining 371 were patients who entered to the emergency rooms with abdominal pain, with appendicitis as a possible diagnosis. A total of 97 of 311 or 31% of patients had pathology-confirmed appendicitis in the study. AppyScore was able to correctly identify 95 of 97 patients with pathology-confirmed appendicitis. This exceptionally high sensitivity level of 98% for detecting the actual disease condition is considered statistically significant (95% CI = 93% to 99.9%). In addition, the combination of using the data from AppyScore in conjunction with a CT scan resulted in a specificity of 99% (95% CI = 97% to 99.9%).
In June 2008, we announced commencement of our 800 patient Clinical Trial for the AppyScore human appendicitis blood-based diagnostic test. This trial is being conducted to support the FDA 510(k) clearance of the AppyScore test product and is expected to be completed in the fall of 2008. As soon as this data is collected, validated, analyzed, and providing the final results reach there target outcomes, we anticipate an immediate filing of our final 510(k) application. Pilot cGMP manufacturing of the AppyScore test kits for use in the trials has been completed. These test kits, representing the final commercial version, are currently in use in the multi-site clinical trial current underway. Clinical study sites have been selected and Institutional Review Board study approvals are in place at the lead hospital sites. The remaining final study approvals are planned to be in place for all sites within the coming weeks. The clinical sites are large hospitals, including a major children’s hospital and clinical trials at all hospital locations may not commence at the same time. Clinical teams have also been assembled and include principal investigators, co-investigators, monitors, technicians, statisticians and coordinators. To help insure a successful trial, AspenBio engaged a highly qualified and experienced Contract Research Organization to plan and direct the trials.
Preliminary data gathered during pre-clinical research trials continues to show the high sensitivity of the AppyScore test in addition to specificity improvements over the previously reported September 2007 research trial data. Results of the pre-clinical pilot studies, using the anticipated final commercial device format manufactured under cGMP, although preliminary, indicate a high sensitivity, consistent with the data from the 2007 research trial. In addition, the specificity trends from these pre-clinical studies are significantly higher (p = 0.007) than specificity shown in the previous 2007 research trial. The company attributes this to improved study design, such as more appropriate patient inclusion criteria, tighter requirements on sample handling and testing, along with controlled manufacturing and quality control of the cGMP device. If this higher specificity is maintained during the official 510(k) trials, we believe it will translate into increased utility, economic benefit, and wider adoption of this blood-based diagnostic since potentially even fewer patients would be subjected to Computed Tomography (CT Scans) once AppyScore is utilized in the clinical decision matrix.
