AppyScore™
Overview
AppyScore™ is a novel, rapid, blood-based diagnostic test to assist physicians in the difficult challenge of evaluating acute appendicitis in the Emergency Department or Urgent Care setting when a patient presents complaining of abdominal pain which could be due to acute appendicitis. AppyScore detects a marker in the blood, MRP 8/14, associated with the inflammation and local infection related to acute appendicitis. AppyScore has the potential to increase the speed and accuracy of identifying patients at low risk for having acute appendicitis, eliminating unnecessary CT scans and reducing radiation exposure risk for patients while also saving the U.S. health care system many millions of dollars annually.
In March of 2010, AspenBio Pharma announced that the Company had completed patient enrollment in its AppyScore pivotal clinical trial designed to evaluate 800 patients suspected of having acute appendicitis. The study has now advanced to the data analysis phase. Results from the study will support a potential 510(k) submission.
The Challenges of Diagnosing Appendicitis
Suspected acute appendicitis is the most common reason for abdominal surgery and each year more than 320,000 appendectomies are performed in the United States.1 Despite this, 25 to 30% of patients are not diagnosed in time—resulting in perforated appendix and emergency surgery. In addition:
- Up to 18% of patients are misdiagnosed and sent home with appendicitis;2
- 8 - 10% of surgeries remove a normal appendix;3
- Women are more difficult to diagnose than men and the negative appendectomy rate can be 50-100% higher in women;3 and
- An estimated 1 million patients present annually with a low risk for acute appendicitis and are exposed to unnecessary CT scan radiation—a potentially significant health risk
When a patient enters the emergency department with abdominal pain, many factors are evaluated. The emergency department (ED) physician will obtain the patient’s history and perform a complete physical exam. Most physicians will also order several laboratory tests including full blood chemistry, complete white blood cell count and a urinalysis. To gain an initial clinical impression the ED physician will factor in the physical findings with the results of the specific blood and urinalysis lab tests. At this point, if concerned about appendicitis they will order a CT scan and/or in some situations an ultrasound will be ordered. Unfortunately, even with the addition of imaging it can be difficult to make an accurate diagnosis of acute appendicitis. Frequently, if the physician is unsure of the diagnosis and other possibilities have been ruled out, the patient will then be sent to surgery for an appendectomy. The current reality for diagnosing acute appendicitis in the US, which is heavily dependent on abdominal CT scanning either results in around 1 in 10 patients having a normal appendix removed , or around 1 in 6 being sent home with appendicitis, due to inaccurate diagnosis,
Market Opportunity: Better Test for Appendicitis
In the U.S. alone, an estimated 6 million people annually enter hospital emergency departments with abdominal pain with appendicitis being a major cause for concern. About 5.6 million of these patients receive lab tests in addition to a physical exam. Additionally, Computed Tomography ("CT") is often used for diagnosing appendicitis because of the lack of other definitive diagnostic tools.
While considered the best diagnostic method currently available, the cost, time and safety concerns associated with CT make it undesirable for use in patients who are at low risk of having acute appendicitis. Recent published studies have raised health concerns about the possible harmful effects of radiation levels in CT scans which increases with multiple scans.
One abdominal CT scan exposes a patient to a radiation dose equivalent to more than 500 chest X-rays. A CT scan can also be difficult to read in children and women, and they often are not conclusive. Diagnosis in women with abdominal pain is also particularly difficult due to common gynecological conditions having symptoms similar to appendicitis. A recent paper released by the FDA "Initiative to Reduce Unnecessary Radiation Exposure from Medical Imaging" February 2010 Center for Devices and Radiological Health U.S. has implications for AppyScore.
Out of these 6 million U.S. annual abdominal pain patients, approximately 320,000 have their appendix removed. Due to limited effectiveness of current diagnostic tools, an estimated 8%-14% of these appendectomy patients were determined to have a normal appendix. This misdiagnosis is estimated to result in more than $400 million a year in unnecessary surgical costs. An independent study also indicates that a significant number of the patients who have appendicitis were initially misdiagnosed and sent home only to return later to the hospital with a more advanced appendicitis or perforation.
Once an appendix is perforated, it may become life threatening and the surgery is more complicated, costly and recuperation time is significantly longer. An estimated 25%-30% of appendicitis cases presenting to the hospital have a perforated appendix. Due to the removal of healthy appendices and misdiagnosis, many appendicitis cases result in litigation.
The AppyScore Solution
To address the need for an objective, quantitative, rapid and safe test to aid in the evaluation of patients suspected of having acute appendicitis is clearly needed. AspenBio has developed a unique blood-based test system called AppyScore to be used in hospital emergency departments. The test incorporates a patented assay that detects a marker in the blood associated with the inflammation seen in appendicitis. AppyScore is anticipated to be the first and only such test available in the world.
Clinical studies show AppyScore's clinical value when used in conjunction with other modalities typically used in evaluating acute appendicitis. This test has the potential to change the standard of care for appendicitis diagnosis if physicians adopt AppyScore as part of the regular blood work they order for people who enter the emergency department complaining of abdominal pain and are suspected of having appendicitis.
Use of AppyScore also has the potential to reduce the number of costly abdominal CT scans and associated exposure to harmful radiation. A physician will typically receive the results of lab work and AppyScore far more rapidly than results from a CT. These factors could enable more effective management of the hospital emergency departments and increase throughput due to the improved ability to distinguish at-risk patients versus those with low probability of appendicitis. Additionally CT scans often take 4-6 hours before results are available.
The company is advancing the FDA 510(k) clearance process of AppyScore with an ELISA-based test while simultaneously completing development and testing of a new rapid assay cassette with reader instrument. The cassette and reader format has many benefits over the ELISA, including:
- Rapid results as compared to the ELISA test format
- A simplified format that significantly reduces operator dependence
- Integratable with a hospital’s Laboratory Information System
Automated reader/cassette
While the ELISA-based AppyScore™ trial has been completed and the company has been advancing toward filing its 510(K) application with the FDA it has also been developing a stand-alone cassette and reader instrument platform. This platform will provide AppyScore results more rapidly and efficiently than the ELISA format and offers many benefits over an ELISA-based test. It can produce results in approximately 15-20 minutes, which in turn can be rapidly and accurately uploaded to a hospital's Laboratory Information System (LIS) via a built-in electronic interface. As a fully integrated, stand alone assay system, it can significantly reduce an operator's processing steps and the corresponding potential for errors.
Clinical trials of cassette and reader instrument platform are planned for 2010 and will be designed to support a 510(k) submission for this rapid assay platform using the ELISA test as a predicate, assuming the ELISA test is cleared by the FDA. In addition, these trials will provide AspenBio and physicians with additional information on the product's clinical utility. In January of 2010, AspenBio announced that the Company entered into a strategic relationship with LRE Medical GmbH (LRE) to complete commercial development and manufacture of the reader instrument to be used with the AppyScore cassette system. LRE is a leader in the development and manufacture of medical devices with a special focus in instruments for point-of-care and near patient testing. LRE is ISO 13485 certified, experienced in manufacturing for in vitro diagnostic and MDD devices requiring the CE mark in the E.U., and is registered with the FDA as a contract manufacturer for medical device products. Additionally AspenBio has recently entered into an agreement with BBInternational for the manufacturer of the cassette which will be used in conjunction with its reader. BBI is a leading OEM provider of lateral flow tests and provides reagents, development services, and contract manufacturing for rapid diagnostic tests for the point-of-care markets.
1CDC 2006 data
2Source: Graff, et al, study
3Wagner, et al Surgery, Ann Surg 2008 Oct;248 (4):557-63
