18 June 2019 - - US-based Alexion Pharmaceuticals, Inc. (NASDAQ: ALXN) has presented new data demonstrating that Ultomiris (ravulizumab), the first and only long-acting C5 complement inhibitor administered every eight weeks, provided consistent efficacy and safety through 52 weeks in the extension1 of the Phase 3 study of Ultomiris and Soliris (eculizumab) in complement inhibitor-naïve, adult patients with paroxysmal nocturnal hemoglobinuria, the company said.
Sustained efficacy of Ultomiris was observed on the co-primary endpoints of transfusion avoidance and normalization of lactate dehydrogenase levels and the secondary endpoints of LDH level reduction and breakthrough hemolysis.
In an additional sub-study, nearly all patients preferred Ultomiris over Soliris.
The data will be presented at the Annual Congress of the European Hematology Association, taking place June 13-19, 2019 in Amsterdam, Netherlands.
LDH level normalisation and reduction are direct markers for reduced hemolysis in PNH, a severe, ultra-rare disease characterized by complement-mediated intravascular hemolysis.
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.
Incomplete inhibition of the C5 complement protein can increase the risk of BTH and related serious complications.
All patients in the initial Ultomiris group of the extension study maintained complete C5 inhibition through 52 weeks, and no patient experienced BTH associated with incomplete C5 inhibition.
All patients who had experienced incomplete C5 inhibition while receiving Soliris in the first 26 weeks achieved complete C5 inhibition after the switch to Ultomiris in the extension phase.
No patient experienced BTH associated with incomplete C5 inhibition between weeks 27 and 52 after switching to Ultomiris compared to 6% while receiving Soliris in the first 26 weeks.
The most common adverse events occurred less frequently in the extension phase than during the initial treatment phase where the safety profile of Ultomiris was consistent with that of Soliris.
The most common treatment-emergent adverse events in the extension phase were upper respiratory tract infection (in the initial Ultomiris arm) and nasopharyngitis (in the initial SOLIRIS arm).
The most frequently observed serious adverse event was pyrexia. One patient in the initial Soliris arm died from lung cancer (unrelated to Soliris treatment).
There was no case of meningococcal infection observed.
Ultomiris was studied in the largest-ever Phase 3 program in PNH. The entire clinical development programme for Ultomiris in PNH to date represents more than 800 patient years of experience.
Additional data to be presented at the EHA congress indicate a very strong patient preference for ULTOMIRIS over SOLIRIS.
According to results from a sub-study in the Ultomiris Phase 3 extension in patients who had been stable on Soliris before, nearly all patients preferred Ultomiris due to reduced infusion frequency, ability to plan activities, overall quality of life, convenience of treatment, and effectiveness of medication until the next infusion compared to Soliris.
New results from the International PNH Registry will also be presented at the EHA congress.
These data suggest that a change in clone size does not change the increased risk of major adverse vascular events in PNH, and that complement inhibition with Soliris does not change the effectiveness of concomitant immunosuppressive therapy in patients with PNH and aplastic anemia.
The US Food and Drug Administration approved Ultomiris for adult patients with PNH on December 21, 2018.
The European Commission is reviewing the recommendation by the European Medicines Agency's Committee for Medicinal Products for Human Use from April 26, 2019 to approve Ultomiris as a treatment for adult patients with PNH and typically delivers its final decision within two months.
The Japanese Ministry of Health, Labour and Welfare is reviewing the recommendation by the Pharmaceuticals and Medical Devices Agency's Drug Committee (BUKAI) to approve Ultomiris as a treatment for patients with PNH and is anticipated to deliver a decision in late June.
One-Year Efficacy of Ravulizumab (ALXN1210) in Adult Patients with Paroxysmal Nocturnal Hemoglobinuria Naive to Complement Inhibitors, EHA Congress, June 13-16, 2019 Amsterdam, Netherlands, oral presentation, June 15, 2019, 12:00 p.m., abstract S863.
Patient Preferences for the Treatment of Paroxysmal Nocturnal Hemoglobinuria: Results of a Patient Survey of Ravulizumab (ALXN1210) and Eculizumab, EHA Congress, June 13-16, 2019 Amsterdam, Netherlands, poster presentation, June 14, 2019, 5:30 p.m., abstract PF734.
Change in Clone Size Does Not Predict Risk of Major Adverse Vascular Events: Results from the International PNH Registry, EHA Congress, June 13-16, 2019 Amsterdam, Netherlands, oral presentation, June 15, 2019, 12:30 p.m., abstract S865.
No Change in the Effectiveness of Immunosuppressive Therapy in Patients with PNH and AA Receiving concomitant Eculizumab, EHA Congress, June 13-16, 2019 Amsterdam, Netherlands, poster presentation, June 15, 2019, 5:30 p.m., abstract PS1117.
At the end of the 26-week Phase 3 study,2 all patients (246; 125 on ULTOMIRIS, 121 on Soliris) had the option to receive Ultomiris every eight weeks for up to two years.
The aim of this extension study is to monitor the durability of efficacy in the initial ULTOMIRIS group, the efficacy of Ultomiris in the initial Soliris group after the switch to Ultomiris and the safety of Ultomiris in all patients.
A total of 243 patients (124 from the initial Ultomiris group, 119 from the initial Soliris group) were followed.
Results for the co-primary endpoints of transfusion avoidance and LDH level normalization and the secondary endpoints of percentage change from baseline in LDH levels and proportion of patients with BTH are provided descriptively.
Complete C5 inhibition was defined as plasma levels of free C5 ≤0.5 μg/ml.