Alexion Announces Positive Phase 3 Data for Long-Acting C5 Complement Inhibitor

Drug manufacturer Alexion has announced positive topline results of a phase 3 study that determined that ALXN1210, a long-acting C5 complement inhibitor, can be safely and effectively switched among patients with paroxysmal nocturnal hemoglobinuria (PNH) currently being treated with the shorter-acting eculizumab (Soliris).

PNH is a rare blood disorder that causes uncontrolled activation of the complement system and results in hemolysis, or the destruction of red blood cells. ALXN1210, like the earlier eculizumab counterpart, works to stop the destruction of red blood cells and prevent PNH from causing clots and organ damage. Significantly, the difference between the 2 drugs is that ALXN1210 is a long-acting inhibitor that only needs to be administered once every 8 weeks. Conversely, patients receiving eculizumab undergo intravenous infusions every 2 weeks.

The study, conducted among 195 adults with PNH in a randomized open-label trial, demonstrated non-inferiority of ALXN1210 to eculizumab in patients with PNH who are stable on eculizumab based on the primary endpoint of change in lactate dehydrogenase (LDH) levels.

Notably, the study also found non-inferiority on all 4 key secondary endpoints: proportion of patients with breakthrough hemolysis, change from baseline in quality of life as determined via the Functional Assessment of Chronic Illness Therapy Fatigue Scale, proportion of patients avoiding transfusion, and the proportion of patients with stable hemoglobin levels. LDH levels fell just shy of statistical superiority to eculizumab.

“The way I look at it, we don’t need the superiority claim to be successful for a fast conversion. We have a strong, differentiated clinical profile, a robust data package,” said Alexion’s CEO, Ludwig Hantson on an investor call, as reported by FierceBiotech.

In addition, the success of this phase 3 trial has positioned Alexion to seek regulatory approval, and potentially stave off market competition from a biosimilar version of eculizumab; currently, drug maker Amgen is developing a biosimilar candidate for the high-cost biologic that is also approved to treat myasthenia gravis.

However, analysts have found that despite this new innovation, payers are still looking to keep the price of eculizumab down, and the availability of new drugs that could equal eculizumab in safety and efficacy could still disrupt its market share.