Alexion's Second C5 Complement Inhibitor Requires Less Frequent Dosing, Carries New Patents

Late last month, Alexion Pharmaceuticals received early FDA approval for ravulizumab-cwvz (Ultomiris), for the treatment of adult patients with paroxysmal nocturnal hemoglobinuria (PNH), a debilitating and ultra-rare blood disorder characterized by complement-mediated destruction of the red blood cells (hemolysis).

It’s Alexion’s second C5 complement inhibitor. The first, eculizumab (Soliris), is currently used to treat patients with PNH. However, the existing biologic must be administered every 2 weeks, versus every 8 weeks for ravulizumab.

Another possible advantage is that the newer drug also has the benefit of new patent exclusivities that could help Alexion stave off the impact of competition from oncoming eculizumab biosimilars. Ravulizumab is also being proposed as a once-weekly subcutaneous dosing option that will be the subject of an upcoming phase 3 study.

In a published report, Credit Suisse analyst Martin Auster said that Soliris is protected by US patents until 2027. European patents end earlier, in 2024.

PNH can cause a wide range of debilitating symptoms and complications, including thrombosis, which can occur throughout the body, and result in organ damage and premature death. The FDA decision had been slated for an FDA meeting next month.

In a statement, Alexion said the approval was based on positive phase 3 data from 2 phase 3 studies that included 441 patients who had either never been treated with a complement inhibitor before, or who had been stable on eculizumab. The company said the efficacy of ravulizumab administered every 8 weeks was noninferior to the efficacy of eculizumab administered every 2 weeks on all 11 endpoints. Safety profiles were similar.

Regulatory authorities in the European Union and Japan have accepted and are reviewing applications for the approval of for ravulizumab as a treatment for adults with PNH.

At a list price of approximately $500,000 per patient per year, eculizumab, which is also approved to treat atypical hemolytic uremic syndrome and generalized myasthenia gravis, is one of the most expensive therapies in the world. It sells for $6543 per vial; the wholesale acquisition cost of ravulizumab is slightly lower at $6404 per vial, the company said in a recent filing, according to Reuters. Reuters also noted that the newer drug has an FDA black box warning for the risk of life-threatening meningococcal infections and sepsis, the same as eculizumab.

Eculizumab competition could come from Amgen, which is currently engaged in a phase 3 study in Spain that evaluates the efficacy and safety of its proposed biosimilar, ABP 959, versus the reference eculizumab in patients with PNH. Also developing a biosimilar is Samsung Bioepis, with its SB12.