2023-05-08 20:21:00
Treatment with iptacopan as oral monotherapy in adult patients with paroxysmal nocturnal hemoglobinuria (PNH) naïve to complement inhibitors (including anti-C5 therapies) resulted in an increase in hemoglobin level equal to or greater than 2 g/dL from baseline without the need for red blood cell transfusions after the main 24-week treatment period (primary endpoint). The figure was estimated in 92.2% of patients based on statistical models and taking into account missing data.
These are summarized results from the Appoint-Pnh Phase 3 study of investigational oral monotherapy with iptacopan that met its primary endpoint and demonstrated clinically meaningful benefits across all secondary endpoints. The data – informs in a note released today by the pharmaceutical company Novartis – were presented for the first time at the recent 49th annual meeting of the European society for blood and marrow transplantation (Ebmt).
“These data underscore the potential of iptacopan as an oral drug to change the clinical management of this devastating disease. In addition to the improvement in hemolysis and fatigue observed with currently available treatments, patients with hemolytic PNH treated with iptacopan also achieve an improvement in anemia not achievable with anti-C5 monoclonal antibodies,” said Antonio Risitano, Md, PhD. investigator co-lead of the study, president of the International Pnh Interest Group and Director of the Hematology and Hematopoietic Transplant Operational Unit of the Reference Center for aplastic anemia and paroxysmal nocturnal hemoglobinuria at the Aorn San Giuseppe Moscati in Avellino. “The results of Appoint-Pnh – adds the other investigator co-lead of the study, the French Régis Peffault de Latour, Md, PhD, of Saint-Louis Hospital, Greater Paris University Hospital – are consistent with the tolerability and safety profiles observed in the Apply-Pnh study and highlighting the possibility of controlling hemolysis with oral iptacopan, with an almost complete elimination of the need for blood transfusions”.
EPN – explains the company – is a rare, chronic and serious haematological disease mediated by complement. Despite treatment with anti-C5 monoclonal antibodies (a component of complement involved in the immune response, ed), it is characterized by significant unmet needs because a large percentage of people with PNH remain anemic, fatigued and dependent on blood transfusions. It is estimated that around 10-20 people per million worldwide suffer from this disease.
The Appoint-Pnh study also showed clinically meaningful benefits in relation to secondary endpoints. An estimated 62.8% of patients achieved hemoglobin levels of 12 g/dL or greater without the need for red blood cell transfusions. “The results of the Apply-Phn and Appoint-Pnh clinical trials – comments Paola Coco, Cso & Medical Affairs Head IM of Novartis Italy – confirm the potential of iptacopan in the treatment of Epn, a disease that heavily impacts people’s lives, which often they find themselves facing difficulties for which an effective response has not yet been identified.While we confidently await the results of the first submissions to the regulatory authorities in the EPN – he adds – we continue to research iptacopan in other complement-mediated diseases with phase III results in other pathologies”.
It is important to underline that an estimated percentage of 97.6% of patients achieved independence from red blood cell transfusions at 24 weeks. No breakthrough hemolysis (Bth) clinical events or major adverse vascular events (Mave) were observed during the 24-week trial period. Lactate dehydrogenase (Ldh) levels decreased by 83.55% from baseline at 24 weeks. Patients also reported clinically meaningful improvements in fatigue with an adjusted mean increase from baseline of 10.75 in the ‘Functional assessment of chronic illness therapy – Fatigue’ score, reaching absolute levels similar to those reported in the general population.
Iptacopan – concludes the note – has demonstrated a profile of tolerability and safety consistent with the data previously reported. The most commonly reported adverse events were infections (in 40.0% of patients, mainly Covid-19 [15,0%] and upper respiratory tract infections [12,5%]), headache (27.5%) and diarrhea (7.5%), with four serious adverse events.
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