Alexion Pharmaceuticals, Inc. (Nasdaq:ALXN) today announced that the U.S. Food and Drug Administration (FDA) has approved the Company's supplemental Biologics License Application (sBLA) providing regular approval for Soliris® (eculizumab) for the treatment of adult and pediatric patients with atypical hemolytic uremic syndrome (aHUS) to inhibit complement-mediated thrombotic microangiopathy (TMA). This update reflects Alexion's fulfillment of post-marketing requirements, including the submission of confirmatory data from two additional prospective clinical trials, including one in pediatric patients with aHUS. The revised label now specifies important longer-term clinical benefit associated with chronic and sustained Soliris treatment with inclusion of results with two years of ongoing treatment in aHUS patients. The updated label also includes data on the use of Soliris treatment prior to use of supportive care with either plasma exchange or plasma in prospective clinical trials.
aHUS is a genetic, chronic, ultra-rare disease defined by immediate and lifelong risk of thrombotic microangiopathy (TMA) resulting in vital organ failure and premature death. Soliris, a first-in-class terminal complement inhibitor, specifically targets uncontrolled complement activation, and is the first and only approved treatment for pediatric and adult patients with aHUS in the United States, European Union, Japan and other countries. Soliris previously received Accelerated Approval (Subpart E) for this indication from the FDA in September 2011. The FDA grants Accelerated Approval to drugs based on an effect on a surrogate or intermediate clinical endpoint that is reasonably likely to predict a drug's clinical benefit. To achieve regular approval, a drug company must usually submit additional data to verify clinical benefit.
"We are pleased that, since 2011, the FDA's Accelerated Approval process has enabled us to provide Soliris to individuals whose lives have been at risk of the severe clinical manifestations of aHUS and who would otherwise have had no safe or effective treatment options," said Leonard Bell, Chief Executive Officer of Alexion. "The results obtained from the two additional prospective clinical trials further confirm the safety, efficacy and life-transforming benefit of chronic Soliris treatment in both adult and pediatric patients with aHUS. The updated label now includes data that specifically supports the longer-term benefit associated with chronic and sustained Soliris treatment. We continue to work with a sense of urgency to bring Soliris to more patients suffering from this life-threatening disease worldwide."
The Clinical Studies section (Section 14.2) of the revised Soliris prescribing information now includes results from a total of four prospective, single-arm studies in patients with aHUS, three in adult and adolescent patients and one in pediatric patients, as well as one retrospective pediatric study, which evaluated the safety and efficacy of Soliris for the treatment of aHUS. Longer-term data of original registration studies demonstrated that chronic and sustained Soliris treatment inhibited complement-mediated TMA and resulted in significant and continuous time-dependent improvements in renal function, and was well tolerated. Importantly, 5 out of 18 patients in the original registration studies who deviated from the approved Soliris dosing, including discontinuation, experienced severe TMA manifestations whereas patients who stayed on therapy had complete inhibition of complement activity, which was sustained through 2 years. Results from the two additional prospective trials conducted by Alexion - one in adult and the other in pediatric patients with aHUS - showed that Soliris inhibited systemic complement-mediated TMA (the formation of blood clots in small blood vessels throughout the body), improved renal function, decreased or eliminated the need for dialysis and was well-tolerated. Efficacy and safety results from the additional prospective clinical trials were consistent with those observed in the original Soliris registration trials.
Two-Year Treatment Outcome Data Provided in Package Insert (C08-002A/B and C08-003A/B)
The updated U.S. Package Insert includes longer-term data in patients from the two initial prospective, multinational registration trials (referred to as Trial 1 and Trial 2). In both Trial 1 and Trial 2, chronic and sustained Soliris treatment inhibited complement-mediated TMA and resulted in significant and continuous time-dependent improvements in renal function through 2 years. In Trial 1, the proportion of patients that achieved hematologic normalization increased from 76% at 26 weeks to 88% at 2 years and the mean eGFR increase by 32 mL/min/1.73m2 from baseline achieved at 26 weeks was maintained through 2 years. Four of the five patients (80%), who discontinued dialysis by 26 weeks remained off dialysis and no patient required new dialysis through 2 years. In Trial 2, the proportion of patients that achieved TMA event-free status increased from 80% at 26 weeks to 95% at 2 years. Also, in Trial 2, patients that had a median of 48 months from aHUS diagnosis to screening for the trial and had sustained longer-term renal damage were observed to have a time-dependent improvement in renal function as measured by eGFR ≥15 mL/min/1.73 m2, which increased from 5% of patients at 26 weeks to 40% of patients at 2 years. In both Trials, responses to Soliris were similar in patients with and without identified mutations in genes encoding complement regulatory factor proteins or auto-antibodies to factor H. The most common serious adverse events (SAEs) with Soliris treatment were accelerated hypertension, hypertension and influenza. There was no increase in SAEs with ongoing Soliris treatment, as rates of SAEs remained steady or declined from the initial 26-week study period to the subsequent treatment periods. There were no deaths from Trial 1 and 1 patient death from Trial 2 due to gastrointestinal bleed after 1.9 years of Soliris treatment that was deemed unrelated to drug.
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