Ladies and gentlemen,

Please find below the new Absorber Newsletter regarding the meeting in Chicago which was held to discuss AbSorber’s endothelial crossmatch test, XM-ONE, November 6, 2010.

Thank you for your attention and best regards

Julia Hirtle
Sales and Marketing Manager Distribution

 
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Clinical Use Of XM-ONE® Discussed At Olerup, Inc. Advisory Board Meeting In Chicago, IL.

Improving outcomes in kidney transplantation: Non-HLA antibodies and Enhanced Clinical Risk Assessmen

On Nov 6, 2010 a meeting was held in Chicago to discuss AbSorber’s endothelial crossmatch test, XM-ONE®, which is distributed in the Americas by Olerup, Inc. In attendance were 15 invited transplant surgeons and nephrologists from leading programs across the United States. The meeting was co-chaired by Professor’s Ron Shapiro of the University of Pittsburgh Medical Center, and Joseph Leventhal from the Northwestern University Feinberg School of Medicine.

“This was a very interesting meeting that provided updated data on the use of the anti-endothelial antibody test. More information will need to be gathered to establish with better precision the role of this test in clinical practice,” Professor Shapiro stated when closing the meeting

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The Development Of XM-ONE®, The Only FDA Approved Crossmatch Available For Non-HLA Testin

Professor Jan Holgersson from Sahlgrenska University Hospital, Gothenburg, Sweden, started by presenting the background facts and rationale for the development of the assay. In the early 90’s a girl receiving a kidney transplant at Karolinska Hospital, Stockholm, Sweden developed a hyper acute rejection and lost the graftwithin hours after transplantation.
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This was subsequently repeated and in parallel this also occurred in another child transplanted at the same center. Both these patients were negative in the standard tests and were shown to have non-HLA anti-endothelial cell antibodies. The researchers found that these cells expressed Tie-2 receptors on the cell surface and that Tie-2 positive antibodies could be used to isolate the cells. These findings have thereafter been explored and developed by AbSorber, and FDA approval was granted in 2008.

Clinical Data Indicates That XM-ONE® Detects Risk For Acute Rejections

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Dr Håkan Hall, Head of Research and Development at AbSorber continued by presenting clinical data and focused on a multicenter study published in Transplantation (Breimer et al, Transplantation, Feb 2009). In the study it was clearly demonstrated that patients being XM-ONE® positive pre-transplant had an increased risk of having acute rejections, compared to patients being XM-ONE® negative (46% vs 11%, p<0.005, fig.1). Furthermore, in the XM-ONE® positive patients all rejections occurred within the first three weeks post transplantation

Dr Hall also presented data from Sweden comparing PRA levels to XM-ONE® positivity/negativity in patients awaiting kidney transplantation. These results indicated that there was a correlation between XM-ONE® positivity and PRA levels. In patients with >10% PRA, they were XM-ONE® positive in 48% of the cases, compared to 24% if PRA levels were <10%. However, in actual numbers there were more patients being XM-ONE® positive among patients with low sensitization (PRA <10%), compared to highly sensitized patients (PRA>10%).

In the multicenter study (Breimer et al) patients that were PRA positive (PRA >10%) before transplantation did not have an increased risk of acute rejections. In the study PRA levels did not significantly impact the rejection frequency (Table 1) but rather the XM-ONE® result. Also in this study the “low risk patients”, i.e. patients having a PRA<10%, were the largest group of patients at risk of having a rejection.

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Ongoing Single Center Study At Northwestern, Interim Report

Dr Joseph Leventhal, Northwestern University, Chicago, IL, presented two datasets, one from a pilot study of 53 patients, and the second from an ongoing prospective ongoing that has thus far recruited 130 patients. In their first study they found that approximately 20% of their patients were tested positive using the XM-ONE® assay, despite being negative for HLA-DSA and MICA-DSA The prospective study, which is currently ongoing, has so far enrolled 130 patients, with clinical data being available for 93 patients having reached at least one month of follow-up.
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In these patients elevated Serum Creatinine above 2mg/dl was found in 42% of the XM-ONE® positive patients (5/12) compared to 15% of the negative patients (12/81, Fig.3). Data on Acute Rejection Episodes are yet to be evaluated.

Data from Johns Hopkins Support Findings From Published Multicenter Study

Dr Annette Jackson from Johns Hopkins presented long term data on 60 kidney transplant patients. Thirty of these patients were part of the large multicenter study of XM-ONE® (Breimer et al) and 30 patients were included recently. Data from the most recent 30 patients was comparable with the Multicenter Study patients, and in total Dr Jackson presented a rejection frequency of 36% among the XM-ONE® positive patients compared to 17% in the negative group. As in the multicenter study, there was also a significant difference in Serum Creatinine with the XM-ONE® positive group having a higher SCr <100 days post transplant. All rejections in the XM-ONE® positive group were classified as cellular rejection based on the Banff ’97 criteria. These criteria were chosen since they were previously used in evaluating patients in the Multicenter Study.

IgG Subclass Determination Of Non-HLA Antibodie

It has previously been described that there is a rank of order for the four different IgG subclass molecules to fix complement, with the affinity for C1q being in the order IgG1>IgG3>IgG2. IgG4 does not bind C1q and, therefore, does not fix complement.

A total of 7 XM-ONE® positive patients had sufficient pre-transplant serum for IgG subclass analysis. Serum was depleted of IgM via hypotonic dialysis. Interestingly, it was found that the sub classes expressed among the XM-ONE® positive sera’s tested were enriched for IgG2 and IgG4. These subclasses very poorly (or not at all) have the ability to activate complement which may elicit rejection and graft dysfunction through mechanisms that are distinct from HLA-specific antibodies.

The study from Johns Hopkins has been submitted for publication and therefore data communicated is limited.

Long Term Data On XM-ONE®

Dr Markus Gäbel, Sahlgrenska University Hospital, Gothenburg, Sweden, presented a four year data follow up on their patients included in the multicenter study. In the data set, which included a total of 53 patients, almost half of the group had received a kidney from a deceased donor, showing that deceased donors can be XM-ONE® tested in a secure way.
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In the Gothenburg data 13% of the patients were positive in XM-ONE® and among those 71% had a rejection during the first three weeks post transplantation. In the XM-ONE® negative group, the rejection rate was 11%. When evaluating the long term data in patients being XM-ONE® positive pre transplant, there was a significantly increased serum creatinine one year after transplantation. However this difference, when compared to XM-ONE® negative patients disappeared greater that one year post transplantation. The Board speculated that this was due to the rejections aggressively being identified and treated at an early stage, thereby avoiding delay in diagnosis and treatment. The Board also encouraged the presenter to look further into the data.

Furthermore Dr Gäbel informed the Board on how the Gothenburg Transplant Team has responded to the need of peripheral blood in deceased donors, thus enabling XM-ONE® testing with patients receiving deceased donor organs. In Gothenburg they have started, during organ procurement, to fill a blood bag (450 ml) by inserting an IVC into the aorta before cold flush. When performing the XM-ONE® assay with blood from these donors the outcome is very much in line with assays run on with living donor organs.

AbSorber are excited about the very positive interest that XM-ONE® has received in the transplant community around the world. The data presented at this symposium further supports the clinical role of XM-ONE® in organ transplantation, according to Anders Karlsson, CEO of AbSorber.

XM-ONE® is a standardized, cell based, crossmatch test for clinical use. The use of XM-ONE® allows you to identify patients at risk for developing acute rejections and post-transplant complications. XM-ONE® provides additional information compared to the currently used lymphocyte crossmatch tests and therefore improves the basis for risk assessment prior to transplantation. For further information please do not hesitate to contact us.

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