On July 7, 2022, biotechnology company Akari Therapeutics, Plc (“Akari”) shared via news release that the first patient in its clinical trial has completed their course of treatment. Within the trial, researchers are evaluating nomacopan for pediatric patients with hematopoietic stem cell transplant (HSCT)-related thrombotic microangiopathy (HSCT-TMA). Currently, no FDA-approved treatment options exist for those with HSCT-TMA. Therefore, if nomacopan shows promise, it could fill a huge unmet need within this patient community.
Nomacopan: An Overview
On its website, Akari explains that nomacopan is:
a second-generation complement inhibitor which acts on complement compound-C5, preventing release of C5a and formation of C5b-9, and independently also inhibits leukotriene B4, or LTB4, activity, both elements that are co-located as part of the immune/inflammatory response.
Nomacopan is a recombinant small protein (16,740 Da) derived from a protein originally discovered in the saliva of the Ornithodoros moubata tick, where it modulates the host immune system to allow the parasite to feed without alerting the host to its presence or provoking an immune response.
Due to the way nomacopan was developed, it can also be administered to patients in a variety of different ways. For example, nomacopan can be administered subcutaneously, topically, intravenously, or via inhalation.
In the United States, nomacopan has received both Fast Track and Orphan Drug designations.
A Nomacopan Clinical Trial
So far, three patients have enrolled within the Phase 3 clinical trial evaluating nomacopan for HSCT-TMA. Altogether, researchers hope to enroll a total of seven patients aged 6 months+. These patients all developed HSCT-TMA within the year following either allogeneic or autologous HSCT. In regards to the three enrolled patients so far, one has completed treatment, one is being dosed, and another died from multi-organ failure with no relationship to treatment.
About HSCT-TMA
In an article by Joseph Rosenthal published in the Journal of Blood Medicine, he explains that HSCT-TMA, or transplant-associated thrombotic microangiopathy, is:
a multifactorial disorder caused by systemic vascular endothelial injury that can be triggered by several mechanisms during the transplant process. A subgroup of patients with thrombotic microangiopathy…may develop other thrombotic microangiopathic disorders such as thrombotic thrombocytopenic purpura.
Rosenthal estimates that HSCT-TMA, a rare multisystem complicationm, affects around 30% of those undergoing HSCT. Unfortunately, in those who develop severe HSCT-TMA, the complication is fatal in around 80% of cases. Patients may experience activation of the compelement system, blood clots, systemic inflammation, hemolytic anemia, oxygen-starved tissues, renal failure, and organ damage and loss of function.
