FDA expands label for Alexion's Ultomiris to include atypical haemolytic uraemic syndrome 

Alexion Pharmaceuticals announced that the FDA approved its filing for Ultomiris (ravulizumab-cwvz) for the treatment of atypical haemolytic uraemic syndrome (aHUS) to inhibit complement-mediated thrombotic microangiopathy (TMA) in adults and paediatric patients aged one month and older. The company noted that this marks the first paediatric approval for the long-acting C5 complement inhibitor, which is already cleared in the US, EU and Japan for adults with paroxysmal nocturnal haemoglobinuria (PNH).

The latest decision was supported by data from two single-arm clinical trials, one involving adults, as well as an ongoing paediatric study that included 14 out of 16 children in the interim analysis. Complete TMA responses were assessed by looking at improvements in haematologic and renal parameters, including platelet count, lactate dehydrogenase and serum creatinine levels.

Alexion previously reported findings from the Phase III ULTOMIRIS aHUS-311 trial of 56 adults showing that in the initial 26-week treatment period, 53.6% of patients achieved a complete TMA response, while interim data from the paediatric study demonstrated a complete TMA response of 71%. Alexion said treatment with Ultomiris led to reduced thrombocytopaenia in 84% of adults and 93% of children, and reduced haemolysis in 77% of adults and 86% of children. The therapy also improved kidney function in 59% and 79% of adults and children, respectively.

"The consequences of uncontrolled complement activation, like organ failure and potentially death, create significant challenges and uncertainty for people and families facing aHUS," commented John Orloff, head of R&D at Alexion. He added that "based on the Phase III data...we believe Ultomiris has the potential to become the new standard of care for this devastating disease." Marketing submissions for Ultomiris to treat aHUS are currently under review with regulators in Europe and Japan.

Alexion is pushing to expand Ultomiris' label as US market exclusivity for Soliris (eculizumab), the company's older drug used to treat aHUS and PNH, is being threatened. According to analysts, Ultomiris is a more convenient option as it needs to be infused only every eight weeks, compared to every two weeks for Soliris. Cowen analyst Phil Nadeau suggested that Ultomiris, which he predicts will generate sales of about $1.5 billion from the aHUS indication by 2024, is also slightly more potent than Soliris.

Ultomiris has a list price of $6404 per vial, versus $6543 for Soliris, which accounts for over 80% of Alexion's total revenues. The yearly cost for Ultomiris maintenance doses is roughly $458,000 on average, a discount of around 33% to the labeled maintenance dose of Soliris in aHUS, Alexion noted. Meanwhile, the therapy is also being tested for use in patients with neuromyelitis optica spectrum disorder and generalised myasthenia gravis.

Alexion recently agreed to acquire Achillion Pharmaceuticals in a deal potentially worth more than $1 billion, gaining the latter's clinical-stage portfolio of oral small-molecule Factor D inhibitors, which are being developed for patients with complement alternative pathway-mediated rare diseases, such as PNH and C3 glomerulopathy. For related analysis, see ViewPoints: Alexion dealmaking could prove a little too complementary.

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