Meeting with Dr. Loirat while at ASN

[Joy Lewis O'Brien]

Dear all,

I had the opportunity Saturday morning to talk with Dr. Chantal Loirat, a pediatric nephrologist and researcher based in France. She told me about a recent study using Soliris (eculizumab) in adult and adolescentpatients with aHUS who are resistant to plasma therapy.

This particular study consisted of 17 patients who had unsuccessfully tried a plasma therapy but had not been able to restore kidney function or platelet counts. Of the seven patients who were on dialysis at the start of the study, five patients were able to stop dialysis completely while receiving Soliris during the study, which lasted 26 weeks. There is an extension to the study, so patients can continue to be treated and researchers can continue to collect data. Dr. Loirat shared three important outcomes from the trial:

1. A "spectacular" increase in platelets after the first treatment with Soliris. Platelet counts remained stable or continued to improve during the study.
2. Improved renal function (2/3 of patients gained at least one stage on the CKD scale within 1-2 months with continued smaller increases in the time period after that)
3. Significant improvement to their quality of life – five times the level that researchers consider to be a meaningful improvement. Dr. Loirat said she believes this is because
   patients avoided the burden of dialysis, and because uncontrolled complement activation can cause extreme fatigue, loss of
   appetite, etc.

This particular study is important as the patient population who are plasma resistant often have poorer responses to therapy than those who are not. They also have fewer treatment options because they do not respond or don’t tolerate plasma therapy. This is an important study because it is a prospective controlled trial, rather than reports on individual patients. Dr. Loirat explained that researchers were hoping and expecting to see positive results, and they were not disappointed.

Dr. Loirat noted that it is critical that patients with aHUS are treated
as soon as possible after an acute episode to minimize further damage to the kidneys, as the best effects were seen in patients who were treated less than a month after their initial episode. She emphasized that this research is very important, but the treatment is not yet approved. Also, every patient is different and families should consult with their physicians before proceeding with any kind of treatment.

I asked for her opinion on whether patients who had been on dialysis for a long
time due to little to no renal function would now be better candidates for transplant using Soliris, since transplant has been off the table for many due to the high rate of recurrence. She told me that in her opinion, yes, patients could be better candidates for the kidney transplant (rather than the dual transplant) but that Soliris should definitely be used at the time of the graft rather than waiting for an acute episode following the transplant surgery. Dr. Loirat said we still have much to learn about this use of complement inhibition, and she reminded me that different genetic mutations/hybrid/polymorphisms have different rates of recurrence so it is critical before a patient considers a transplant that they be thoroughly genetically tested in order to minimize those risks and tailor the transplant protocol.

I also asked her if she thought that if patients who had some kidney function remaining could ever expect to regain that kidney function using Soliris, enough to avoid transplant. Dr. Loirat feels that there is a good possibility that kidney function can be stabilized using Soliris, so that patients won't continue to lose function, and there may be some slight gains over time. For patients that had a sudden decrease in renal function, the gains look better than those who have slowly been losing function over time, since the latter patients may have scar tissue in the kidneys that cannot be rescued. Of course at this time we don't know the long term results of Soliris as a treatment, so it's impossible to say that patients could avoid transplant forever, but from the small window of time that we've seen, it looks as if transplant could at least be postponed for a while given the stabilizing effect of Soliris. Dr. Loirat mentioned that we need more experience and more clinical data to see if this true.

Finally, we talked a little bit about the pediatric trial that just opened. The
guidelines for the trial are posted on the Alexion website and at www.clinicaltrials.gov, identifier number NCT01193348. This new trial will enroll patients as young as one month and as old as 18 years. Patients may be
newly diagnosed, previously diagnosed, or previously diagnosed with a kidney transplant. In order to make it a study that can be scientifically valid, the trial has to have patients who are similar in their disease presentation. There is no obligation for patients to currently be on plasma therapy. However, the patient needs to be thrombocytopenic, meaning they are experiencing an acute episode at the time of the trial. For children who are not eligible for the trial, physicians can contact Alexion, the company sponsoring the study, to see if the drug could be made available. Regulations are different in each country. Saturday afternoon I went to some sessions on transplants followed by a presentation about eculizumab and the plasma resistant patients. I'll keep you posted!

Thank you,

Joy

[Bill Biermann]

I would encourage all parents to email this to their Pediateic Nephrologist.   they are propably aware of this, but it will reinforce what they may have already discovered.  Thanks Joy

[Cheryl Biermann]

Thank you for sharing this information with us, Joy. It was nice to hear the comments from Nicolas about her as well as Maria's comments...it is really a very small community of wonderful people, isn't it?

[Nicolas]

Hello,

Professor LOIRAT is THE specialist in France of the AHUS. She is following group of patients throughout the country. It is fantastic. It gives the impression that every child is hers (like a grandmother to her grandchildren).

I await his comeback to France to get a return on the ASN.
Thank you for your explanations.

Nicolas

[maria vicenta carratala rios]

dear Joy:
sometimes I have contact with Dr a Cantal Loirat by e mail and she had been very kind to answer me about any question. I knew Veronique Fremeaux in ahus last conference in Innsbruck, and anothers doctors ahus team. I think that ina a short time spanish nephrologist will speak about the Jose case and the use of soliris in a kidney trasplant. Of course I Will send a copy to the ahus foundation.