Appendicitis Product Pipeline
Approximately 5-7% of the world’s population will get appendicitis in their lifetime. Appendicitis is a common acute surgical problem primarily affecting children and young adults under 30 years of age. It typically is an acute event that occurs between 24 and 36 hours from the initiation of symptoms to the point where, if it is not operated on and removed, it will perforate or burst causing a potentially life threatening event for the patient. We estimate that there are approximately 700,000 cases of appendicitis annually in the United States and approximately 6,000,000 patients enter US emergency rooms annually complaining of abdominal pain. An accurate diagnosis at a sufficiently early stage is a significant factor in achieving a successful patient outcome; however this is difficult to achieve using the current standard of care. Additionally, conventional methods are expensive, subjective and difficult because there is considerable overlap of genuine appendicitis symptoms with other clinical conditions. Misdiagnosis of appendicitis can lead not only to unnecessary surgery but also to delay of proper therapy for the actual underlying condition thereby increasing the chances of life threatening perforation. Today in the United States, despite the extensive use of use of CT scans to help diagnose the condition prior to surgery, 1 in 7 appendectomies remove a normal appendix due primarily to incorrect diagnosis. In addition, approximately 100,000 patients suffer a perforated (or burst) appendix because they are not diagnosed in time. A dilemma for surgeons is minimizing the negative appendectomy surgery rate without increasing the incidence of a life threatening perforation among patients referred for suspected appendicitis. To date, (prior to the development of AppyScore™) there is no individual sign, symptom, test, or procedure capable of providing a reliable diagnosis of appendicitis.
Recent published research indicates that the removal of a perfectly normal appendix may have negative implications for the patient and that previous beliefs that the appendix did not have a functional use for the body may be erroneous. A dilemma for surgeons is minimizing the negative appendectomy surgery rate without increasing the incidence of perforation among patients referred for suspected appendicitis. Techniques currently used by emergency room doctors to diagnose millions of patients complaining of abdominal pain are expensive, time consuming, and can have high error rates. After performing basic ER tests and a physical health examination, a CT scan is the most commonly used emergency room diagnostic method for ruling out appendicitis for patients with abdominal pain which often results in long delays due to scheduling and reading of the scans. Currently the total estimated cost of a CT scan plus associated fees, range from $1,500 to 3,000 and get as high as $5,000, per procedure resulting in an estimated total of $6.0 to $9+ billion being spent annually in the US on CT scans to diagnose appendicitis. The scans can take more than four hours to complete (including typical processing time) and expose many patients unnecessarily to high levels of ionizing radiation. While CT scans are still the current medical standard for diagnosing appendicitis, CT diagnostic error rates are estimated to range between 15% and 40%, and a high percentage of CT scans are simply inconclusive or non-diagnostic. The present approach contributes to a significantly large number of unnecessary (negative) appendicitis surgeries and or false-negative diagnosis due to diagnostic errors.
In addition to involving other risks, hospital charges for unnecessary (negative) appendectomies are estimated to cost approximately $1.5 to $2.0 billion annually in the US alone. Additionally up to 30% of patients are not diagnosed correctly in time and suffer a potentially life-threatening perforation of the appendix requiring immediate and more complex emergency surgery. Due to a very high risk of serious internal infection, perforated appendix cases require a more lengthy hospital stay, longer recovery or treatment period, substantially increased cost and tremendous discomfort for the patient. Appendicitis is also one of the leading causes of litigation and claims of medical malpractice due to many factors including high diagnostic error rates, negative appendectomies, and increased cost and complications in cases where appendix perforates (bursts).
Appendicitis most frequently occurs in patients aged 10 to 30, but can affect all ages. The appendicitis condition usually involves abdominal pain. Appendicitis is especially difficult to diagnose in children and young adults using a CT scan because many patients in this age group have low body fat resulting in very poor tissue differentiation / contrast on the CT scan. We believe our appendicitis triage/screen blood tests could be particularly helpful in ruling out the disease in the highest-risk appendicitis population of children and young adults. Our new blood-based appendicitis triage/screen tests also have the potential to enhance overall safety by reducing the amount of radiation exposure from unnecessary CT scans.
Based upon a potential annual emergency room/urgent care usage of 6 million tests and management’s estimates of a sales price of a few hundred dollars per test with modest adoption, the annual U.S. market potential for AppyScore and AppyScreen systems could exceed several hundred million dollars. We believe the market potential for our appendicitis screen test systems worldwide will be a multiple of that of the U.S.
The Company continues to make progress in the development and testing of its two first-generation blood-based human diagnostic tests designed to rapidly help diagnose or rule out appendicitis in patients complaining of abdominal pain. Specifically, we have created and optimized a specialized test to detect a marker in the blood associated with appendicitis and have tested this assay in several on-going clinical research trials involving hundreds of human patients.
Preliminary results indicate that our first-generation ELISA triage/screen test is highly effective in identifying patients with acute appendicitis. This marker demonstrates a linear (or direct) correlation with the severity of appendicitis. The test is especially accurate in patients 30 years of age and under, which is also the age group most commonly afflicted with appendicitis.
A large independent research report (Graff et al., 2000 Acad Emerg Med Vol 7 n 11 pp 1244-55) of approximately 1,026 appendicitis patients from 12 hospitals across the northeastern United States reported that an average of 18.6% of patients (ranging from 10.6% to 27.8% per hospital) were incorrectly diagnosed as not having appendicitis and were sent home, only to return to the emergency room with acute appendicitis in an advanced or perforated (burst) condition. If the Graff report is representative of the state-of-the-art diagnostics for appendicitis, then the 98% sensitivity level of AppyScore demonstrates the substantial impact this screening test could have for life threatening misdiagnoses. The false negative diagnosis of appendicitis could become much less frequent using AppyScore, resulting in fewer patients with appendicitis being erroneously sent home.
AppyScore™ and AppyScreen™ (Blood Testing Systems)
Our primary test, the AppyScore system, which is based on a blood test result scoring system, is designed to be used as an initial appendicitis triage/screen test for patients entering an emergency room /urgent care facility complaining of abdominal pain. We anticipate that our new appendicitis triage/screen test will be easily incorporated in routine blood testing as a patient’s blood sample is taken in the ordinary course of an initial health exam of any patient entering the emergency room. Our appendicitis blood test scoring system is designed to numerically measure the blood marker level, which guides the physician in determining not only the presence but also the potential stage or severity of appendicitis being experienced by the patient. Determining the severity of appendicitis could help the physician assess the level of possible danger and the potential for the appendix to burst or perforate, causing life-threatening complications.
The FDA’s Center for Devices and Radiological Health (CDRH) is responsible for regulating firms who manufacture, repackage, re-label and or import medical devices sold in the US. Medical devices are classified into Class I, II and III. Currently our two new appendicitis tests are classified as non-invasive Class II medical devices by the FDA which will require Premarket Notification 510(k) clearance by FDA. Typically an FDA 510(k) clearance does not require lengthy approval requirements or processes. Therefore we anticipate being able to obtain an FDA 510(k) approval of our first appendicitis blood test AppyScore prior to the end of 2008 or within the first months of 2009. Generally FDA product approvals are granted after specific clinical trials, GMP validations and quality control requirements have been achieved to the agencies satisfaction. Any product approvals that are granted remain subject to continual FDA review, and newly discovered or developed safety or efficacy data may result in withdrawal of products from marketing. Moreover, if and when such approval is obtained, the manufacture and marketing of such products remain subject to extensive regulatory requirements administered by the FDA and other regulatory bodies, including compliance with current GMP, adverse event reporting requirements and the FDA’s general prohibitions against promoting products for unapproved or “off-label” uses. Manufacturers are subject to inspection and market surveillance by the FDA for compliance with these regulatory requirements. Failure to comply with the requirements can, among other things, result in warning letters, product seizures, recalls, fines, injunctions, suspensions or withdrawals of regulatory approvals, operating restrictions and criminal prosecutions. Any such enforcement action could have a material adverse effect on our business. Unanticipated changes in existing regulatory requirements or the adoption of new requirements could also have a material adverse effect on our business.
