The FDA accepts Alexion Pharmaceutical Inc.’s BLA for review for approval of ALXN1210 for the treatment of patients with paroxysmal nocturnal hemoglobinuria.
The US Food and Drug Administration (FDA) has accepted Alexion Pharmaceuticals, Inc.’s Biologics License Application (BLA) for review for approval of ALXN1210 for the treatment of patients with paroxysmal nocturnal hemoglobinuria (PNH), a rare, acquired, life-threatening disease of the blood.
As part of an expedited 8-month review instead of the standard 12-month review following Alexion’s use of a rare disease priority review voucher, the FDA has set a Prescription Drug User Fee Act (PDUFA) date of February 18, 2019.
A long-acting C5 inhibitor, ALXN1210 works by hindering the C5 protein in the terminal complement cascade; this portion of the body’s immune system plays a central role in several rare disorders when activated in an uncontrolled manner. If approved, ALXN1210 will be the first and only long-acting complement inhibitor for patients with this chronic, progressive, ultra-rare disease.
The application is supported by data yielded from 2 pivotal phase 3 trials which were a part of the largest-ever phase 3 program associated with PNH. In one of the trials, investigators sought to compare the safety and effectiveness of ALXN1210 compared with Soliris. To do this, 246 adult patients with PNH who had not received previous treatment with a complement inhibitor and presented with lactate dehydrogenase (LDH) levels ≥ 1.5 times the upper limit of normal (ULN) at time of screening were enrolled in the trial; all participants had at least 1 of the following symptoms within 3 months of screening: fatigue, hemoglobinuria, abdominal pain, dyspnea, anemia, history of a major adverse vascular event, dysphagia, erectile dysfunction, or a history of packed red blood cell (pBRC) transfusion associated with PNH.
Patients were randomized into 2 treatment arms: those who would receive a single loading dose of ALXN1210 followed by regular maintenance dosing every 8 weeks and those who would receive 4 weekly induction doses of Soliris, followed up with regular maintenance dosing bi-weekly. Both arms of the trial received treatment for the duration of 26 weeks.
The investigational treatment was found to be noninferior to Soliris, thus meeting co-primary endpoints of transfusion avoidance and normalization of LDH levels as well as secondary endpoints, percentage change from baseline in LDH levels, change from baseline in quality of life as assessed by the Functional Assessment of Chronic Illness Therapy-Fatigue scale, proportion of patients with breakthrough hemolysis, and proportion of patients with stabilized hemoglobin levels. Investigators noted that the safety profiles for both drugs were similar.
For the ALXN1210 PNH Switch Study, investigators again sought to evaluate the safety and effectiveness of ALXN1210 compared with Soliris in 195 adult patients with PNH ≥ 18 years of age; all patients had LDH levels ≤ 1.5 times the ULN and had been treated with Soliris for at least the past 6 months before the trial. Again, the investigational therapy was administered intravenously every 8 weeks, while Soliris was given every 2 weeks for the duration of 26 weeks. The investigators followed up the treatment period with an extension period in which all patients received the investigational therapy every 8 weeks for up to 2 years.
The trial showed that patients with PNH can safely and effectively switch over from treatment with Soliris to treatment with ALXN1210, going from having to receive treatment every 2 weeks to receiving treatment every 8 weeks. Additionally, again the trial demonstrated that ALXN1210 was noninferior to Soliris in patients with the disease who had been stable on Soliris.
“We are working with the FDA to facilitate a smooth review,” John Orloff, MD, executive vice president and head of research and development at Alexion, said in a recent statement. “Building on comprehensive results from the largest-ever phase 3 development program in PNH, 11 years of proven efficacy and safety with Soliris, and 25 years of leadership in complement biology, we are on track with our efforts to establish ALXN1210 as the new standard of care for patients with PNH.”
Alexion has already submitted a New Drug Application (NDA) in the United States and in the European Union (EU), and now, they are in the process of submitting one in Japan. The European Medicines Agency has already accepted the NDA and is reviewing the submission for the EU. The therapy has already received an orphan drug designation in both the United States and EU for the treatment of PNH.