By Mary Welch
Data from a Phase III trial of LeukoScan (sulesomab) for patients with acute atypical appendicitis were released for the first time and showed the diagnostic imaging agent developed by Immunomedics Inc. correctly predicted in 97 percent of the patients that surgery would be unnecessary.
The Phase III trial involved patients with suspected acute, atypical appendicitis and presented a diagnostic problem to the emergency department physician or managing surgeon.
According to the company, appendicitis is the most commonly missed diagnosis in patients with abdominal pain who are seen in emergency rooms. In addition, it is among the top malpractice claims against ER physicians in the U.S. The problem is that classic signs, such as pain in the right lower quadrant with rebound tenderness, may be absent in some patients ¿ or difficult to confirm, such as with children.
Therefore, some patients are needlessly operated on while others are mistakenly sent home or admitted into the hospital for observation.
¿The opportunity to reduce unnecessary surgeries and decrease hospitalization is important in today¿s age of managed care,¿ said Cynthia Sullivan, Immunomedics¿ executive vice president. ¿But that must be balanced by the unacceptable risk of premature discharge. The challenge is for a rapid, accurate, diagnostic test with a very low rate of false-negative studies.¿
LeukoScan is prepared by adding a common isotope, technetium-99m, to a small amount of the antibody drug targeting the white blood cells associated with an acute infection. The formula can be prepared and injected into a patient in about five minutes. Nuclear imaging scans may be obtained as early as 30 minutes after injection.
¿This potentially makes it perfect for emergency rooms,¿ she added.
In December 1996, Immunomedics, of Morris Plains, N.J., submitted its Biologics License Application for LeukoScan for three indications: acute atypical appendicitis, osteomyelitis (bone infection) and osteomyelitis in the setting of diabetic foot ulcers.
The Phase III study showed that among the 141 children and adults enrolled from February 1995 through June 1997, a true-positive rate of 91 percent and a negative predictive rate of 97 percent for acute appendicitis were achieved. Of those patients, 84 percent were enrolled with a clinical suspicion of appendicitis, whereas 73 percent had anorexia, nausea or vomiting, 46 percent had leukocytosis and 41 percent had a low-grade fever.
Thus, LeukoScan could correctly predict in 97 percent of the patients that surgery would be unnecessary. It was also reported that LeukoScan would have changed clinical management or reduced additional diagnostic studies in 64 percent of the patients.
Prior to the patients receiving LeukoScan, the treating physicians recommended close hospital observation in 84.4 percent of the cases; after LeukoScan, that number was 55.6 percent. Prior to LeukoScan, doctors recommended that 11.1 percent of the patients be sent home; after treatment, that number was 32.6 percent. Those sent to surgery were 28.2 percent of the patients prior to LeukoScan imaging vs. 30.4 following imaging.
In addition, LeukoScan was able to detect other abdominal diseases that later were confirmed by surgery. Among those diseases were carcinoid, pericecal phlegmon, salpingitis, an appendiceal abscess, a nonvisualized gall bladder and inflammation.
¿LeukoScan had a tolerable safety profile,¿ Sullivan said. ¿It is also difficult to assess whether some of the side effects were due to LeukoScan or to the patient¿s problem. Abdominal discomfort was a reported side effect, which is also very similar to what you would experience if you were suspected of having an appendicitis.¿
Nine patients reported a total of 10 non-serious side effects including diarrhea, post-surgical dysuria, itching and agitation as well as transient eosinophilia and monocytosis. However, no immune response was found in any of the patients.
¿These side effects were without clinical significance and, again, it¿s hard to say that one thing led to these to these side effects,¿ Sullivan added.
The data, published in the March issue of Surgery, contain the results of the Phase III trial conducted by the LeukoScan Appendicitis Clinical Trial Group.
¿This is the first publication of our results,¿ Sullivan said. ¿Our application is still pending and continues under active review with the FDA.¿
Immunomedics¿ stock (NASDAQ:IMMU) closed Tuesday at $2.562, up 18.75 cents.