Rare Disease Report

Journal Watch - Soliris' RCTs for Treating aHUS Published

JUNE 07, 2013

The two clinical trials that were instrumental in getting Sorilis’ orphan drug approval for atypical hemolytic uremic syndrome (aHUS) in 2011 were published this week in the New England Journal of Medicine. The publication confirms the data available in Soliris’ PI and reconfirms the positive impact this drug can have on patients with aHUS.

aHUS is a chronic and life-threatening condition that is caused by uncontrolled activation of the complement system and leads to the formation of blood clots in small blood vessels throughout the body known as thrombotic microangiopathy (TMA).   If left untreated, patient often have multiple complications leading to stroke, heart attack, kidney failure, and death. Until Soliris was approved, treatment was limited to plasma exchange/infusion with limited long term effectiveness.

The publication, authored by Dr Legendre et al detailed two prospective, multicenter Phase 2 trials in which aHUS received Soliris for 26 weeks (followed by long term extensions). The first study (Trial 1) enrolled 17 fairly newly diagnosed (mean duration 9.7 months) aHUS patients with low platelet counts and substantial kidney damage with clinical evidence of progressing TMA. Trial 2 enrolled 20 patients with chronic renal insufficiency, prolonged use of plasma exchange or infusion, and long-term aHUS (median 48 months). The primary end points included a change in the platelet count (in trial 1) and thrombotic microangiopathy event–free status (no decrease in the platelet count of >25%, no plasma exchange or infusion, and no initiation of dialysis) (in trial 2).

The results of the study showed that primary endpoints were met in both trials. In trial 1 , the mean increase in the count from baseline to week 26 was 73×109 per liter (P<0.001) and the 5 of 5 patients in that group were able to discontinue dialysis.. And at the end of trial 2, 80% of the patients had thrombotic microangiopathy event–free status.  The study also found that Soliris was associated with significant improvement in all secondary end points. In addition, no cumulative toxicity of therapy or serious infection-related adverse events, including meningococcal infections, were observed through the extension period.

The authors of the study concluded that Soliris “inhibited complement-mediated thrombotic microangiopathy and was associated with significant time-dependent improvement in renal function in patients with atypical hemolytic–uremic syndrome.”

In a press release by Alexion, lead author Dr. Christophe Legendre of the University of Paris Descartes and Hôpital Necker in Paris, France stated, “Soliris represents a substantial advance in the treatment of patients who suffer from aHUS, because it directly targets chronic, uncontrolled complement activation, the underlying cause of the progressive organ failure and shortened life span of patients with aHUS,”  

The press release also noted that Alexion is work diligently to get Soliris to as many patients as possible. "We are working with a sense of urgency to bring Soliris to more patients suffering from this life-threatening disease worldwide,” said study co-author Camille Bedrosian, M.D., senior vice president and chief medical officer of Alexion Pharmaceuticals, Inc. “In these clinical trials, earlier intervention with Soliris, in order to achieve the complete and chronic inhibition of terminal complement activity, substantially improved the health of a broad population of patients with aHUS.”

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