Smarting from a patent defeat for cash cow Soliris in Europe, Alexion has dulled the pain with a phase 3 readout that sets up new filings for follow-up Ultomiris.
The top-line data comes from a study of the complement C5 inhibitor in patients with atypical hemolytic uremic syndrome (aHUS), an indication which made up a chunk of Soliris’ (eculizumab) predicted sales of almost $3.5 billion last year.
In the trial, Ultomiris (ravulizumab) met its targets of improving blood profile and kidney function, with more than half (53.6%) of patients with the ultrarare disease having a complete thrombotic microangiopathy (TMA) response within 26 weeks, says Alexion. The data means it can file for approval in the first half of the year.
aHUS causes progressive damage to vital organs, predominantly the kidneys, leading to kidney failure and premature death, and complement mediated-TMA—inflammation and blood clotting in small blood vessels—drives the disease pathology.
Ultomiris is billed as an improved version of Soliris that is more effective, more convenient to administer and cheaper—having been launched at a 10% discount to Soliris’ $500,000-plus annual price tag after it was approved for paroxysmal nocturnal hemoglobinuria in December.
Approval in aHUS will give Ultomiris two of Soliris’ current stable of three approved indications, which also includes anti-acetylcholine receptor antibody-positive generalized myasthenia gravis (gMG). Alexion’s phase 3 trial of the new drug in gMG is due to start early this year.
In the aHUS trial, an infusion of Ultomiris was given every eight weeks, which compares to the infusions needed every two weeks with Soliris. The new drug was able to bring platelet levels back to normal in 84% of patients and restore red blood cells to normal ranges in 77%. Kidney function measured using serum creatine levels was improved by at least 25% in just under 59% of subjects in the trial. To meet the TMA complete response threshold, a patient had to achieve all three criteria at the same time at least once in the six-month study period.
“The results met the high bar of complete TMA response, defined by hematologic normalization and improved kidney function,” said Alexion R&D head John Orloff, M.D., who reckons the drug can become the “new standard of care for patients with aHUS.”
“We are preparing regulatory submissions for Ultomiris in aHUS in the U.S., European Union and Japan as quickly as possible,” he added.
Alexion needs to switch patients on Soliris to the new drug quickly, after suffering a setback last week when the European Patent Office voted down patents on the drug, raising the risk of biosimilar competition from the likes of Amgen as early as 2022. Soliris accounts for around 90% of all Alexion’s revenues.
Alexion is also hoping to defend its complement inhibitor franchise with a subcutaneous formulation of ravulizumab that could allow once-weekly dosing by subcutaneous injection rather than infusion. It has also been signing bolt-on deals to swell its pipeline, buying rare disease biotechs Syntimmune and Wilson Therapeutics and licensing RNA interference candidates from Dicerna last year.