Rare Disease Report

Kidney Week 2015: Long-Term Data with Soliris (eculizumab) is Impressive

NOVEMBER 08, 2015
James Radke, PhD
Long-term data for the use Soliris (eculizumab) in patients with atypical hemolytic uremic syndrome (aHUS) show that the orphan approved drug is safe and effective for several years.
 
At the 2015 American Society of Nephrology (ASN) Annual Meeting (aka Kidney Week) in San Diego, Jan Menne, MD, of Hannover Medical School, Hannover, Germany reported long term treatment with Soliris in adult patients with aHUS had significantly lower rate of TMA events rate with Soliris compared with discontinuation of Soliris therapy.1
 
In the study, a total of 87 patients with aHUS were monitored. Seventy-six patients had on-treatment periods (median 45.9 months) and 39 patients had off-treatment periods (median 20.1 months) during the observational trial. 
 
For the primary endpoint, researchers reported that the thrombotic microangiopathy (TMA) event rate was 63% lower during periods of Soliris treatment compared to periods of treatment discontinuation. The rate of TMA events during periods of on-label dosing of Soliris was 74% lower than during periods of treatment discontinuation and 57% lower compared with periods when patients were on treatment but receiving non-labeled dosing.
 
The study also observed that off-treatment periods were more frequently associated with serious adverse events and hospitalizations related to TMA events compared with on-treatment periods. The researchers noted that the TMA event rate was 3.5 times higher after Soliris discontinuation versus the rate for patients taking Soliris.
 
Regarding safety, 1 patient died during the observational study due to intensive care complications and multi-organ failure determined to be caused by coexisting disease and unrelated to Soliris. Two patients reported meningococcal infections during the observational study; both were determined to be probably related to Soliris. Both patients recovered and no changes to Soliris dosing were made.
 
In a press release, Dr Menne stated, “Reducing the severity and overall occurrence of TMA events and related complications is a primary objective in the management of patients with aHUS. Findings from this study, which demonstrated a significantly lower TMA event rate with Soliris treatment—particularly when on-label dosing was followed—compared with treatment discontinuation, reinforce the recommendation for long-term Soliris treatment reflected in the prescribing information to reduce the ongoing risk of TMA complications in patients with aHUS.”

Soliris in Children with aHUS 

Gema Ariceta, MD, P.D, of the Hospital Universitario Materno-Infantil Vall d'Hebron, Barcelona, presented a post-hoc analysis of safety data from 3 prospective clinical trials in 28 pediatric (<12 years of age) and adolescent (12-17 years of age) patients with aHUS treated with Soliris. 
 
The most common treatment-related adverse events reported by 1 year of Soliris treatment were skin/subcutaneous tissue disorders including alopecia, dermatitis, eczema, erythema and rash, and infections/infestations including ear infection, fungal infection, nasopharyngitis, and oral fungal infection.
 
Six serious treatment-related adverse events by end of the study (mean 67 weeks) were reported in 4 patients viral upper respiratory tract infection (n=2), influenza peritonitis, respiratory syncytial virus infection, and pyelonephritis (n=1 each)].
 
Researchers concluded that treatment with Soliris is well tolerated in pediatric patients with aHUS, with a safety profile consistent with the broader patient population of the clinical trial program.

About aHUS and Soliris

aHUS is a chronic, ultra-rare, and life-threatening disease that can lead to progressive renal  problems. A common problem in these patients is formation of complement-mediated thrombotic microangiopathy (TMA) – or blood clots in small blood vessels throughout the body. According to Alexion, 65% of all patients with aHUS die, require kidney dialysis, or have permanent kidney damage within the first year after diagnosis despite plasma exchange or plasma infusion (PE/PI). 

Soliris is a recombinant humanized monoclonal IgG2/4 antibody that targets the terminal portion of the complement cascade and has been found to inhibit TMA in patients with aHUS. Soliris is approved in the United States, Europe, Japan, and elsewhere to treat patients with paroxysmal nocturnal hemoglobinuria (PNH) and atypical hemolytic uremic syndrome (aHUS). Soliris is also being invested for other indications, including antibody-mediated rejection3 which was also presented at the ANS meeting.

 References

  1. Menne J, Delmas Y, Rondeau E, et al. Eculizumab Prevents Thrombotic Microangiopathy in Atypical Hemolytic Uremic Syndrome Patients: Long-Term Follow-up. Poster presented at the American Society of Nephrology Annual Meeting, San Diego, November 6. Abstract TH-PO446.
  2. Ariceta G, Greenbaum L, Wang J, et.al. Safety of Eculizumab in Pediatric Patients with Atypical Hemolytic Uremic Syndrome. Poster presented at the American Society of Nephrology Annual Meeting, November 5. Abstract TH-PO460.
  3. Glotz D, Russ G, Rostaing L, et al. Eculizumab in Prevention of Acute Anti-body Mediated Rejection in Sensitized Deceased-Donor Kidney Transplant Recipients: Updated 12-Month Outcomes. Poster presented at the American Society of Nephrology Annual Meeting, San Diego, November 7. Abstract SA-PO1122.
 

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