Novartis targets Alexion's fiefdom after showing PNH patients can safely switch from Soliris

Novartis has presented midphase data showing paroxysmal nocturnal hemoglobinuria (PNH) patients can safely transition from Alexion’s Soliris to its experimental oral candidate LNP023.

The open-label phase 2 evaluated the effect of adding LNP023, Novartis’ small-molecule inhibitor of the alternative complement pathway, to the standard of care in PNH patients. The trial was mainly designed to assess whether daily dosing of LNP023 on top of PNH standard of care, namely Alexion’s blockbuster intravenous infusion Soliris, reduces chronic hemolysis over the first 13 weeks.

Novartis emerged from the trial with data to support the use of LNP023 as an add-on therapy in PNH patients who have active hemolysis despite treatment with Soliris. Lactate dehydrogenase (LDH), the biomarker used to assess chronic hemolysis, fell significantly upon treatment with LNP023. The range of LDH declines after 13 weeks of treatment spanned from 34% to 81% across the 10-patient study. LDH at baseline was 539 U/L.

The researchers also tracked changes in hemoglobin levels, which rose by 2.87 g/dL from baseline. Eighty percent of the participants experienced transfusion-free hemoglobin normalization by week 13. Red blood cell populations increased. All the subjects required transfusions at baseline.

After completing the 13-day study, all participants enrolled into an extension period that had tracked the participants for between 92 and 392 days as of the cutoff. No patients have required red blood cell transfusions. 

The improvements led seven patients who had taken LNP023 for at least six months as an add-on therapy to discontinue Soliris. None of the patients who switched to taking LNP023 as a single agent suffered falls in hemoglobin, changes in biomarkers of disease activity or symptoms of breakthrough hemolysis.

No participants suffered treatment-related serious adverse events or thromboembolic events prior to the cutoff date for the analysis. However, one participant has since stopped taking LNP023 after experiencing lymphoproliferative disorder. The serious adverse event happened in a patient who had severe lymphopenia when they enrolled in the clinical trial.

Buoyed by the data, Novartis Chief Medical Officer John Tsai, M.D., discussed plans for further evaluations of LNP023 with a view to establishing the oral drug as a monotherapy and new standard of care in PNH.

Novartis will face competition as it tries to muscle in on the PNH market. Alexion is building on the dominant position it established with Soliris by promoting its long-acting C5 inhibitor Ultomiris and developing oral factor D inhibitors ALXN2040 and ALXN2050 as an add-on therapy and single agent, respectively. 

Apellis Pharmaceuticals is going after the market, too, with subcutaneous prospect pegcetacoplan, which outperformed Soliris in a phase 3 trial earlier this year. All of the contenders will likely need to compete with biosimilars in the coming years. After reaching a deal with Alexion, Amgen is clear to introduce a Soliris biosimilar in 2025.