Sickle cell disease treatment entered a new era! Adakveo, a P-selectin inhibitor of Novartis, was approved by the US FDA to reduce the frequency of pain crisis

November 18, 2019 / BIOON / - Novartis, a Swiss pharmaceutical giant, recently announced that the US Food and Drug Administration (FDA) has approved adakveo (crizanlizumab, formerly known as seg101) to reduce the frequency of vascular obstructive crisis (VOC) or pain crisis in sickle cell disease (SCD) adults and pediatric patients aged 16 and over It is worth mentioning that adakveo is the first and only targeted biological agent approved by FDA to play a therapeutic role by combining P-selectin Previously, the FDA has granted adakveo breakthrough drug qualification and priority review P-selectin is a kind of cell adhesion protein, which plays a central role in the multicellular interaction leading to vascular occlusion Adakveo's approval marks a new era in SCD treatment, and Novartis expects the drug to be available in the coming weeks The dosage of adakveo was 5mg / kg, intravenous infusion for 30 minutes, once in the first and second weeks, and once every four weeks Sickle cell disease (SCD) refers to a group of inherited red blood cell diseases, named after the "C" or "sickle" shape of red blood cells Patients with SCD are prone to develop vascular occlusive crisis (VOC), especially vascular occlusive pain crisis, which is also the main reason for patients with SCD to seek medical services, but currently there are very limited programs to prevent VOC VOC is triggered by cell clusters that are adherent or blocked by blood cells, and is associated with increased incidence rate and mortality Adakveo can effectively reduce multicellular adhesion by targeting P-selectin This approval is based on positive data from the phase II sustain clinical study This is a multicenter, multinational, randomized, placebo-controlled, double-blind, 12-month study designed to assess the efficacy and safety of adakveo combined with or without hydroxyurea therapy in the prevention of VOC in patients with SCD The results showed that Adakveo (5mg/kg) significantly reduced the median incidence rate of VOC in 45.3% (1.63 vs 2.98, p=0.010) compared with placebo in combination or without hydroxyurea therapy No matter the SCD genotype or the use of hydroxyurea, the VOC frequency was significantly reduced in clinic In addition, the study also showed that the proportion of patients in adakveo (5 mg / kg) group who did not experience any VOC during the treatment period was more than twice that of placebo group (36% vs 17%, P = 0.010), the median time to receive the first VOC treatment was three times that of placebo group (4.07 months vs 1.38 months, P < 0.001), and the median annual hospital stay decreased by 42% (4.00 vs 6.87, P = 0.45) In terms of safety, the most common adverse reactions (incidence ≥ 10%) in patients receiving 5 mg / kg adakveo (n = 111) included back pain, nausea, fever and joint pain Most of the adverse reactions were mild to moderate (grade 1 or 2) Severe (grade 3) arthralgia and fever were 0.9% (1 case) According to the analysis, no patient stopped treatment due to adverse reactions In the sustain study, there was no significant increase in overall infection (53.0% vs 53.2%) or neutropenia (3.1% vs 6.5%) adverse events reported in the adakveo group compared to the placebo group VOC, also known as sickle cell pain crisis (SCPC), is a kind of unpredictable and extremely painful event, which can lead to serious acute and chronic life-threatening complications and death VOC can also lead to large use of health care It is the most common reason for emergency room visits and hospitalization of SCD patients The average lifetime medical cost of each patient is about $1 million, and the total annual medical cost in the United States is more than $1.1 billion In patients with SCD, when multiple blood cells stick together and adhere to blood vessels, VOC will occur, leading to obstruction Reducing blood cell and vascular viscosity may help reduce the number of days a patient experiences VOC The active component of adakveo is crizanlizumab, which is an anti-P-selectin monoclonal antibody It can selectively bind P-selectin on the surface of endothelial cells and platelets in blood vessels, leading to the blocking of P-selectin and inhibiting the interaction among endothelial cells, platelets, red cells, diseased red cells and white cells P-selectin is one of the main drivers of vascular occlusive crisis (VOC), which is a pain complication of SCD Adakveo is currently being developed for VOC prevention in patients with SCD Sustain is a part of sentry clinical research project, which includes a number of clinical studies, aiming to obtain comprehensive data of crizanlizumab for clinical management of SCD The original source: new Novartis medicine adakveo ® (crizanlizumab) approved by FDA to reduce frequency of pain judgments in individuals living with sick cell disease