Alexion clinches aHUS approval for Ultomiris as the clock ticks on Soliris conversion
Alexion has racked up a second approval for Ultomiris, the successor therapy to Soliris, as its mainstay blockbuster therapy faces a patent review process that could drastically shorten its patent exclusivity.
The FDA OK for atypical hemolytic uremic syndrome (aHUS) on Friday was widely expected after Alexion posted a full slate of positive Phase III data in January. But regulators also flagged concerns about serious meningococcal infections, slapping a black box warning on the label and mandating a REMS.
The late-stage results, which included only adults, were “broadly comparable to existing Soliris data in similar patient populations, but with added convenience of every 8 week dosing,” SVB Leerink analysts Geoffrey Porges noted at the time.
Among 56 enrolled, 53.6% demonstrated a complete response after 26 weeks, measuring up to a 56% historic response rate for Soliris.
While another Phase III in pediatric and adolescent patients is still ongoing, the company disclosed that in the initial treatment period 71% of children demonstrated a complete response. Out of 16 patients, 14 were evaluated for that interim analysis. The FDA went ahead and cleared it for use by infants as young as one month old, marking the first pediatric approval for the drug.
Drugs for aHUS — a chronic, progressive ultra-rare disease that can have devastating effects on the kidneys — are measured by their abilities to clear blood clots in small blood vessels throughout the body, or thrombotic microangiopathy (TMA).
Ultomiris works by inhibiting uncontrolled complement activation, specifically blocking the C5 pathway. It’s also approved in the US and Europe as a therapy for paroxysmal nocturnal hemoglobinuria.
“The consequences of uncontrolled complement activation, like organ failure and potentially death, create significant challenges and uncertainty for people and families facing aHUS,” said John Orloff, head of R&D, in a statement. “Based on the Phase 3 data, which demonstrated clinically meaningful benefits in people with aHUS, we believe ULTOMIRIS has the potential to become the new standard of care for this devastating disease.”
Convincing physicians and patients would be crucial. In August, the US Patent Trials Appeal Board (PTAB) agreed to conduct an inter partes review on Soliris after Amgen, which is pushing a biosimilar to the complement inhibitor, launched an effort to overturn patents on the active ingredient.
If Amgen prevails, Soliris’ exclusivity could expire as early as 2022. Credit Suisse’s Martin Auster has previously modeled a roughly 80% conversion to Ultomiris in three to four years across the PNH and aHUS franchises.
The baton is now in the commercial team’s hands.
Porges expects US conversion efforts for Ultomiris to begin immediately, with the EU and Japan to follow next year. From his note out late Friday:
We estimate 2020 US Ultomiris aHUS revenues of ~$140mm, increasing to ~$640mm in 2025, representing ~72% of combined US Soliris/Ultomiris aHUS sales. We continue to remain optimistic about the prospects for Alexion’s complement franchise and believe further indications of rapid conversion across indications and geographies, as well as further life-cycle management opportunities from the Achillion (ACHN, MP) acquisition (assuming FTC clearance), could increase Alexion’s growth outlook over both the near- and longer-term; and potentially draw investors back into the stock over the next 6-12 months.