Express Potential first! The Novartis complement inhibitor phase 3 trial met the primary endpoint

Novartis recently announced that its new drug iptacopan has achieved positive results in a phase 3 clinical trial for the treatment of paroxysmal nocturnal hemoglobinuria (PNH), and the hemoglobin level of patients has continued to increase
significantly after treatment.
Novartis expects to submit an application to regulators in 2023, and if approved, it will be the first oral monotherapy
in the field of PNH treatment.

PNH is a rare complement-mediated blood disorder that is estimated to be newly diagnosed with PNH
in about 1-2 people per million people worldwide each year.
The complement system is part of the innate immune system and improves the ability of antibodies and phagocytes to
attack and remove pathogens from the body.
Some hematopoietic stem cells of PNH patients are mutated, making red blood cells prone to premature destruction by the complement system, which in turn causes intravascular and extravascular hemolysis, anemia, thrombosis, fatigue and a series of other symptoms
.
At present, some anti-C5 therapy drugs have been approved for the treatment of PNH worldwide, but a considerable proportion of PNH patients still suffer from anemia and fatigue after receiving anti-C5 therapy and rely on blood
transfusions.

Ipatapan is an inhibitor drug that specifically targets complement factor B, a key protein
that replaces the complement pathway.
Ipatapan acts upstream of the C5 complement pathway, preventing both intravascular and extravascular hemolysis of PNH
.
From the mechanism of action, iptacopan may have a therapeutic advantage over anti-C5 therapy, which targets a key link in the biological mechanism that leads to the development of PNH, providing patients with an oral monotherapy option
.

Image source: 123RF

The trial met two primary endpoints, one of which was to assess the percentage of patients whose haemoglobin levels improved by 2 g/dL or more from baseline after 24 weeks of treatment without transfusion; Another primary endpoint was to assess the percentage of
participants whose haemoglobin levels were stable at 12 g/dL or more after 24 weeks without blood transfusion.
Secondary endpoints included percentage of participants who remained non-transfusion, mean change in hemoglobin levels, change in fatigue, mean change in absolute reticulocyte values, mean percentage change in lactate dehydrogenase (LDH) levels, rate of breakthrough hemolysis, and rate of
major adverse vascular events.

According to the top-line results released this time, compared with patients receiving anti-C5 therapy, the proportion of patients who received iptacopan (200 mg twice daily) over 24 weeks had hemoglobin levels increase by more than 2 g/dl from baseline and did not require blood transfusion
.
In addition, compared with anti-C5 therapy, there was a statistically significant increase
in the proportion of patients in the iptacopan group who did not require blood transfusions at 24 weeks.
Ipatacopan is well tolerated and its safety profile is consistent
with previously reported data.

Image source: 123RF

Dr.
Shreeram Aradhye, president and chief medical officer of Novartis Global Drug Development, said in a press release: "These positive Phase 3 top-line results highlight the therapeutic innovation potential
of iptacopan for patients suffering from debilitating anemia and lifelong transfusion burden due to PNH.
We look forward to discussing this data with regulators to bring this alternative complement pathway inhibitor to PNH patients
as the first 'first-in-class' oral therapy.
" ”

It is reported that iptacopan is also being tested in PNH patients who have not received complement inhibitor therapy, and Novartis expects to announce the results
in the next few months.
In addition, Novartis is exploring other indications for iptacopan – including PNH, IgA nephropathy (IgAN), C3 glomerulopathy (C3G), atypical hemolytic uremic syndrome (aHUS) and immune complex-mediated membranoproliferative glomerulonephritis (IC-MPGN) – where there are also significant unmet medical needs
.

Recently, the field of PNH treatment has made frequent progress, and a variety of drugs are "at the same end" against their common enemies according to different mechanisms of action, which is expected to bring patients more diversified treatment options, which is of great significance
to meet the huge medical needs in the field of PNH treatment.