According to the www.pharnexcloud.com monitoring of Yaorongyun data, in April 2024, Novartis China announced that the innovative drug ® Iptacopan (Iptacopan hydrochloride capsule) was approved by the National Medical Products Administration (NMPA) of China for the treatment of adult patients with paroxysmal nocturnal hemoglobinuria (PNH) who have not received previous complement inhibitor therapy. Just four months after the approval of the U.S. Food and Drug Administration (FDA), Ipicopam Hydrochloride Capsule was successfully approved in China, which is another example of Novartis' "China speed" to accelerate the entry of global innovative drugs into China, and also a manifestation of Novartis' commitment to focusing on the needs of Chinese patients and supporting the construction of a healthy China.
Yaorong Cloud Data www.pharnexcloud.com
The approval in China is based on the results of a pivotal Phase III global and Chinese subgroup clinical study of APPOINT-PNH (50% of patients enrolled in China).
In the Phase III APPOINT-PNH study of Iptacopan in patients with PNH, the primary endpoint was 92.2% of patients with a baseline increase in hemoglobin of more than 2 g/dL, and the secondary endpoint was 62.8% of patients with hemoglobin levels greater than 12 g/dL and 97.6% of patients avoided transfusions. Another pivotal phase III APPLY-PNH study showed that iptacopan was significantly superior to continued anti-C5 therapy in adult patients with PNH who still had residual anemia despite C5 therapy. The proportion of patients with haemoglobin levels greater than 2 g/dL from baseline was higher in the Iptacopan group (82.3% vs. 2.0%) and the proportion of patients with haemoglobin levels greater than 12 g/dL (68.8% vs. 1.8%) compared with eculizumab/ravulizumab. There is also a slight gap between the two in terms of side effects, ipracopam has a higher chance of headache (16.1% vs. 2.9%), diarrhea (14.5% vs. 5.7%), and infection (38.7% vs. 48.6%).
Iptacopan is a new oral drug, a world-class first-in-class specific Complement Factor B inhibitor (Complement Factor B inhibitor), which acts on the proximal pathway of the complement bypass pathway of the immune system, which can fully control intravascular hemolysis and extravascular hemolysis, make up for the shortcomings of anti-C5 antibody therapy, and create a new era of PNH targeted therapy. It is worth noting that another large indication, IgA nephropathy (IgA nephropathy), has submitted new drug applications in multiple places.
In clinical studies, ipracepam monotherapy 200mg/time twice daily was used, which is more convenient for patients to take than C5 inhibitors that require injection.
About the disease, paroxysmal nocturnal hemoglobinuria (PNH)
PNH is a rare, chronic, and severe complement-mediated blood disorder. Patients with PNH develop acquired mutations in hematopoietic stem cells (located in the bone marrow that can grow and develop into red blood cells, white blood cells, and platelets) that produce red blood cells that are susceptible to premature destruction by the complement system, leading to intravascular hemolysis (red blood cells being destroyed in blood vessels) and extravascular hemolysis (red blood cells being destroyed in the spleen and liver), which manifests as anemia (low levels of circulating red blood cells), thrombosis (formation of blood clots), and other debilitating symptoms.
It is estimated that about 10-20 people per million people worldwide have PNH. Although PNH can occur at any age, it is common in people between the ages of 30 and 40. There is a huge unmet need for PNH that cannot be fully addressed by anti-C5 therapy (eculizumab or ravulizumab). That is, after anti-C5 therapy, a large proportion of PNH patients still have residual anemia and transfusion dependence.
Reference:
NMPA/CDE;
Yaorong Cloud Data www.pharnexcloud.com;
FDA/EMA/PMDA;
public disclosure by the relevant company;
Novartis; www.novartis.com；
https://mp.weixin.qq.com/s/SzzsQvgjdb9aSAPf3de2gg；
Novartis' blockbuster drug Fabhalta® (iptacopan) was approved by the FDA, the first oral monotherapy for PNH in adults, which can improve hemoglobin levels without blood transfusion;
A.M. Risitano, et al. Oral complement factor B inhibitor iptacopan monotherapy improves hemoglobin to normal/near-normal levels in paroxysmal nocturnal hemoglobinuria patients naÏve to complement inhibitors: Phase III APPOINT-PNH trial. OS12-06; 2023 EBMT；
Cançado RD, Araújo A da S, Sandes AF, et al. Consensus statement for diagnosis and treatment of paroxysmal nocturnal haemoglobinuria. Hematol Transfus Cell Ther. 2021; 43(3):341-348. doi:10.1016/j.htct.2020.06.006；等等。