EHA Monthly Dosing of Anti-C5 Antibody Showing Promise in PNH Patients

James Radke, PhD

Alexion announced data from their Phase 1/2 study testing monthly dosing of the anti-C5 antibody, ALXN1210, in patient with paroxysmal nocturnal hemoglobinuria (PNH) yielded highly significant results.
In the study, all 13 patients with PNH receiving ALXN1210 showed rapid and sustained reduction in lactate dehydrogenase (LDH), a marker of hemodialysis.

What is PNH

Paroxysmal nocturnal hemoglobinuria (PNH) is an acquired rare disorder characterized the complement system destroying red blood cells to early. Red blood cells are missing the PIG-A gene that allows glycosyl-phosphatidylinositol (GPI) to help certain proteins stick to cells. PNH is the only hemolytic anemia caused by an acquired (rather than inherited) intrinsic defect in the cell membrane.

The only orphan drug currently approved for PNH is Alexion’s Soliris (Eculizumab) which is an anti-C5 antibody administered biweekly.  The treatment of PNH is directed at the specific symptoms that are present in each individual and includes a variety of different therapeutic options.

Soliris halts the breakdown of red blood cells and can reduce the risk of thrombosis and improve overall quality of life. It is administered biweekly.
Other treatment options for PNH patients are symptomatic and the only cure for the condition is a bone marrow transplant but that is generally not recommended.

Data Presented at the Congress of the European Hematology Association (EHA)

In a poster session, interim results were presented from a Phase 1/2, open-label, 24-week dose-escalating study of ALXN1210 in patients with PNH. Patients with PNH (aged 18 and older; n=13) with mean LDH levels ≥3 times the upper limit of normal and who were complement inhibitor-naïve were separated into two study cohorts. Patients in Cohort 1 (n=6) received either 400 mg or 600 mg induction doses of ALXN1210, followed by a 900 mg maintenance dose once-monthly. Patients in Cohort 2 (n=7) received 600 mg and 900 mg induction doses of ALXN1210, followed by an 1,800 mg maintenance dose once-monthly.

The primary efficacy endpoint was the percent change in LDH levels from baseline.
All patients showed rapid reductions in mean LDH levels at at the first test point (Day 8) and that reduction was sustained for the 5 month interim evaluation period. Patients in Cohort 1 had a reduction in LDH of 85.4% and those in Cohort 2 had a reduction of 86%.

Of the 5 patients with 1 or more transfusions in the year prior to the study, only 1 patient required a transfusion during treatment with ALXN1210. This patient received 2 units of packed red blood cells (RBC) while receiving ALXN1210, compared to 12 units of RBC in the six months prior to ALXN1210.

To date, no serious adverse events, infusion site reactions, drug discontinuations, or adverse events leading to withdrawals have been observed. The most common treatment-emergent adverse events was headache (n=2).
“In a press release, Martin Mackay, PhD, Executive Vice President and Global Head of R&D at Alexion said,  “Interim results from the Phase 1/2 study of ALXN1210 in patients with PNH showed rapid, complete, and sustained complement inhibition, as measured by reductions in LDH levels, with a once-monthly dosing regimen in all treated patients. A Phase 2 study is ongoing to evaluate the safety and efficacy of ALXN1210 in additional dosing cohorts evaluating longer dosing intervals.”
Lead author Jong-Wook Lee, M.D., of The Catholic University of Korea, Seoul St. Mary’s Hospital, Seoul, Korea stated,  “PNH is a devastating, ultra-rare blood disorder caused by uncontrolled activation of complement, putting patients at risk for severe and life-threatening consequences. ”
 Dr Lee added, “The interim data presented at EHA suggest that treatment with ALXN1210 results in effective blockade of complement-mediated hemolysis and reduces transfusion requirements in patients with PNH. All patients achieved rapid decreases in LDH levels that were sustained through extended, once-monthly dosing intervals, consistent with the longer half-life of ALXN1210.”


Lee JW, Bachman E, Aguzzi R, et al. ALXN1210, a long-acting C5 inhibitor, results in rapid and sustained reduction of LDH with a monthly dosing interval in patients with PNH: preliminary data from a dose-escalation study (Abstract 4126). Poster presented at 21st Congress of the European Hematology Association (EHA), Copenhagen, Denmark, June 9-12, 2016. Abstract 4126.
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