Source: European Medicines Agency (EU) Revision Year: 2018 Publisher: Immunomedics GmbH, Otto-Röhm-Straße 69, D-64293 Darmstadt, Germany
Pharmacotherapeutic group: Diagnostic Radiopharmaceuticals
ATC code: VO4D
At the concentrations and activities used for diagnostic procedures, LeukoScan does not appear to exert any pharmacodynamic effects.
The antibody (IMMU-MN3) recognizes an antigenic structure shared by a surface glycoprotein (NCA-90) of granulocytes and the tumour marker, carcinoembryonic antigen (CEA).
In a single-group, open-label, uncontrolled study of 53 patients with acute or chronic infections of unknown origin or extent, doses of LeukoScan from 0.1 mg to 1.0 mg were studied. There was no doseresponse effect for imaging efficacy (sensitivity or specificity) over antibody doses ranging from 0.1 mg to 1.0 mg.
In vitro studies have demonstrated that LeukoScan has no effect on either up-regulation or downregulation of granulocytes, but LeukoScan does appear to bind more avidly to activated rather than resting granulocytes.
On the basis of two controlled clinical trials of LeukoScan to demonstrate the safety and effectiveness of this product for defining the presence and location of osteomyelitis, in a total of 175 evaluable patients, LeukoScan had a sensitivity of 88.2%, a specificity of 65.6%, an accuracy of 76.6%, a positive predictive value of 70.8%, and a negative predictive value of 85.5%.
In a subgroup of patients in whom LeukoScan was compared directly to the currently available 111In-labelled (occasionally 99mTc-labelled) autologous white blood cell (WBC) scanning test, LeukoScan showed a statistically significant increase in sensitivity over that achieved by WBC scanning (87.7% vs. 72.6%, p=0.003 by McNemar’s Test), with no discernible decrease in specificity as compared to WBC imaging (67.1% vs. 69.4%).
The clinical results indicate that among different presentations of osteomyelitis, LeukoScan can show different results. The product is more sensitive (93.9% vs. 80.6%), but less specific (51.6% vs. 72.9%), in diagnosing osteomyelitis in patients with diabetic foot ulcers than in patients with other sites of long bone osteomyelitis. However, there is an equivalent diagnostic accuracy between these two presentations (77.5% vs. 75.8%, respectively). This difference is perhaps explained by the anatomically and pathophysiology more complicated clinical setting of osteomyelitis in the diabetic foot, making differentiation of soft tissue and bone infection more difficult than in other presentations of long bone osteomyelitis.
An evaluation of potential clinical impact of LeukoScan demonstrated that LeukoScan could change clinical management in 50.2% or improve clinical outcome in 43.4% of the 175 evaluable patients with suspected osteomyelitis. In 49.7% of the patients, LeukoScan was presumed to provide clinical benefit not achievable by other available diagnostic imaging methods, with the potential that the diagnosis could have been made by LeukoScan alone in 70.3% of the patients. These benefits were also accompanied by a substantial reduction (85.4%) in the number of patients who would require other diagnostic imaging procedures.
Since LeukoScan cross-reacts with CEA, it should be borne in mind that it may interact with CEA producing tumours.
Pharmacokinetic studies were performed after the intravenous administration of the product. At one hour after infusion, the blood level was 34% of baseline, 17% at four hours and 7% of baseline at 24 hours. The distribution half-life was approximately 1.5 hours; the route of excretion is essentially renal with 41% of the radiolabel excreted in urine over the first 24 hours after administration.
Only very limited nonclinical studies have been performed with either the labeled or unlabeled agent. These revealed no remarkable findings. It should be noted, however, that these studies did not assess genotoxicity, carcinogenic potential, or toxicity to reproduction.
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