Drug for aHUS effective but expensive


Attendees at the 17th Annual
Congress of the EHA
Photo courtesy of EHA

AMSTERDAM—Eculizumab elicits “phenomenal” results in atypical hemolytic uremic syndrome (aHUS), according to two presentations given at the 17th Annual Congress of the European Hematology Association.

But, as one speaker pointed out, the drug may prove too expensive for a lot of patients.

“It’s the most expensive drug I’ve ever come across in my entire life,” said Adrian Newland, MD, of Barts and The London School of Medicine and Dentistry in the UK.

He noted that the drug costs about £400,000 per year in the UK. And reports have listed the US cost at around $400,000 per year.

Expense aside, the drug elicits “dramatic” improvements in aHUS patients, according to Dr Newland. And he presented data to support that statement during an EHA-JSH joint symposium on platelet disorders.

Ramon Vilalta, MD, of Hospital Vall d’Hebron in Barcelona, Spain, also presented favorable results with eculizumab at the meeting, as abstract 1155.

Dr Vilalta began his presentation by pointing out that aHUS is a life-threatening disease that results in multi-organ damage caused by thrombotic microangiopathy (TMA). And plasma exchange/plasma infusion (PE/PI) therapy does little to alter the poor prognosis in this patient population.

“Our patients—pediatric patients mainly—develop end-stage renal failure and even die, despite treatment [with PE/PI],” he said. “[E]culizumab is an anti-C5 terminal complement blocker that could give some hope in the treatment of these patients.”

In an attempt to prove this theory, Dr Vilalta and his colleagues retrospectively analyzed 19 patients with aHUS. Patients—who ranged in age from 2 months to 17 years—received eculizumab for a median of 6 months (range, less than 1 month to 16 months).

All 19 patients had renal complications prior to receiving eculizumab, and 10 had renal and extra-renal complications. Eight patients had baseline platelet counts less than 150 x 109/L. Eight patients were on dialysis at the start of therapy, and 6 patients had undergone kidney transplant.

The first thing the researchers noticed was that eculizumab increased patients’ platelet counts within a week of administration. And this effect was maintained throughout the study period.

Seven of the 8 patients (88%) with abnormal platelet counts at baseline achieved normalized platelet counts. And 89% of all the patients (17/19) had platelet counts of 150 x 109/L or greater at the data cutoff point.

Eculizumab also reduced the burden of disease, Dr Vilalta said. He and his colleagues observed a significant reduction in the TMA intervention rate, which included the number of PE/PIs and new dialysis events. There were a median of 2 interventions per patient per week before treatment initiation, and a median of 0 interventions during treatment (P<0.0001).

None of the patients required new dialysis, and eculizumab eliminated the need for dialysis in 50% of patients (4/8).

Dr Vilalta also pointed out that eculizumab demonstrated similar efficacy regardless of patients’ mutation status or age. He added that the drug appeared to be well-tolerated, although the retrospective nature of the study did not allow for the full collection of drug-specific adverse events.

Of the side effects the researchers did observe, most were mild or moderate. Nine patients experienced pyrexia, 6 had diarrhea, 6 developed an upper respiratory tract infection, 5 developed a cough, 4 experienced vomiting, 4 had nasal congestion, 4 had tachycardia, and 1 patient developed a meningococcal infection during follow-up.

Dr Newland presented similar results from another study of eculizumab in aHUS. He discussed the results during an EHA-JSH joint symposium on platelet disorders, but the study was also presented at ASH last year as abstract 193.

The study included 17 aHUS patients who received eculizumab for a mean of 58 weeks. All of the patients achieved event-free status, which was defined as 12 weeks or more of stable platelet count, no PE/PI, and no new dialysis. Additionally, 4 of 5 patients were able to discontinue dialysis as a result of treatment with eculizumab.

As in Dr Vilalta’s study, treatment was similarly effective in patients with or without complement regulatory factor mutations. And the drug was generally well-tolerated. Twelve patients experienced adverse events, 1 of which was severe.

“[Eculizumab] showed phenomenal results here,” Dr Newland said. “Patients, particularly those treated earlier in their disease, were able to normalize their renal function.”

He said such an improvement is “dramatic” for this patient population, as 25% of aHUS patients die with the first attack, and 50% go into end-stage renal disease. Therefore, eculizumab can be considered the standard of care for aHUS patients—“if [they] can afford it.”

Next Article: