Trial Shows Iptacopan Lowers Need for Blood Transfusion in Almost All Patients With Paroxysmal Nocturnal Hemoglobinuria


The APPOINT-PNH study showed that twice-daily LNP023 (Iptacopan) helped patients with paroxysmal nocturnal hemoglobinuria control intravascular hemolysis.

Administration of twice-daily LNP023 (Iptacopan; Novartis) produced a 2 g/dL or more hemoglobin-level increase from baseline in patients withparoxysmal nocturnal hemoglobinuria (PNH) without the need for red blood cell transfusions after a 24-week treatment period(RBC), according to a study presented at the 49th Annual Meeting of the European Society for Blood and Marrow Transplantation (EBMT).

Credit: Svetlana -

Credit: Svetlana -

The results showed that an estimated 97.6% (95%CI: 92.5, 100) of patients achieved red blood cell transfusion independence at 24 weeks compared with 70% who received blood transfusions in the 6 months prior to treatment.

“In addition to improvement of hemolysis and fatigue seen on currently available treatments, hemolytic PNH patients treated with iptacopan achieve improvement of anemia never seen before with anti-C5s; these data underscore the potential of iptacopan to be a practice-changing oral medicine for this devastating disease,” trial principal co-investigator Antonio Risitano, MD, PhD, president of the International PNH Interest Group and head of the Hematology and Hematopoietic Transplant Unit, Reference Center for Aplastic Anemia and Paroxysmal Nocturnal Hemoglobinuria at the AORN San Giuseppe Moscati, Avellino, Italy, said in a press release.

PNH may affect up to 20 people per million worldwide. The rare and serious complement-mediated blood disorder causes patients to produce RBCs, which are prematurely destroyed within blood vessels (intravascular hemolysis), resulting in anemia, fatigue, and other debilitating symptoms that lower quality of life.

Often treated with anti-C5 therapies, many of these patients continue to depend on RBC transfusions. LNP023 is an investigational orally administered targeted factor B inhibitor that acts upstream of the C5 pathway to prevent hemolysis and decrease the need for transfusions.

The phase 3, multinational, multicenter, open-label, single-arm APPOINT-PNH (NCT04820530) trial evaluated the safety and efficacy of 200 mg twice-daily oral LNP023 treatment in 40 adults with PNH who were not previously treated with a complement inhibitor therapy (anti-C5).

The primary endpoint was proportion of patients with a 2 g/dL or more increase in hemoglobin levels from baseline without the need for blood transfusion at 24 weeks. Secondary endpoints were sustained hemoglobin levels of 12 g/dL or more without need for transfusion, transfusion independence, reduction of lactate dehydrogenase (LDH) levels, rate of breakthrough hemolysis, and change in fatigue.

The study met its primary endpoint with 92.2% of complement-inhibitor-naïve patients achieving a 2 g/dL increase in hemoglobin levels from baseline without the need for transfusion. LDH levels also decreased by 83.5% from baseline to 24 weeks, which suggests there is less RBC destruction, according to the investigators.

The investigational therapy also improved fatigue from baseline, according to scores based on scores from the Functional Assessment of Chronic Illness Therapy, and at least 62.8% of patients achieved 12 g/dL hemoglobin levels without the need of RBC transfusion. Results from the encore APPLY-PNH (NCT04558918) trial suggest superiority of LNP023 to anti-C5 in patients with residual anemia who had already been treated with an anti-C5.

LNP023 treatment matched previously defined tolerability and safety profiles, and investigators anticipate a target action date of sometime during the first half of 2023.

“We continue to be impressed by the totality of evidence from APPLY-PNH and APPOINT-PNH, which confirm the practice-changing potential of iptacopan in the treatment of PNH,” said David Soergel, MD, global head, Cardiovascular, Renal and Metabolism Development Unit, Novartis, in the press release.


Novartis. Novartis Phase III APPOINT-PNH trial shows investigational oral monotherapy iptacopan improves hemoglobin to near-normal levels, leading to transfusion independence in all treatment-naïve PNH patients. News Release. April 26, 2023. Accessed on April 27, 2023.

Related Videos
pharmacy oncology, Image Credit: © Konstantin Yuganov -
Pharmacist holding medicine box in pharmacy drugstore. | Image Credit: I Viewfinder -
Pharmacy Drugstore Checkout Cashier Counter | Image Credit: Gorodenkoff -
Mayo Clinic oncology pharmacy
Testicular cancer and prostate cancer concept. | Image Credit: kenchiro168 -
Medicine tablets on counting tray with counting spatula at pharmacy | Image Credit: sutlafk -
Capsules medicine and white medicine bottles on table | Image Credit: Satawat -
Human cell or Embryonic stem cell microscope background | Image Credit: Anusorn -
Concept of health care, pharmaceutical business, drug prices, pharmacy, medicine and economics | Image Credit: Oleg -
© 2024 MJH Life Sciences

All rights reserved.