Jak1 inhibitor! The first-line treatment of acute graft-versus-host disease (aGVHD) with incite itacitinib, a partner of Cinda biology, failed in critical phase III!

January 6, 2020 / BIOON / - Cinda biological partner Incyte company recently announced the results of the critical phase III gravitas-301 study (nct03139604) on the first-line treatment of acute graft-versus-host disease (aGVHD) with JAK inhibitor itacitinib and corticosteroids This is a randomized, double-blind, placebo-controlled study that evaluated itacitinib or placebo combined with corticosteroids as the first-line therapy for patients with aGVHD The primary end point was the overall remission rate (ORR) on day 28 of treatment, defined as the proportion of patients who showed complete remission, very good partial remission, and partial remission The key secondary end point was non recurrent mortality (NRM) at month 6, defined as the proportion of patients who died from causes other than cancer recurrence Other secondary endpoints included duration of remission (DOR) The results showed that the study did not reach the primary end point: on the 28th day of treatment, the first-line treatment of aGVHD with itacitinib + corticosteroid regimen improved the overall response rate (ORR), but the data did not reach a statistically significant difference (74.0% vs 66.4%, P = 0.08) In addition, there was no difference between the treatment group and the placebo group in the study's key secondary endpoint, non recurrent mortality (NRM) at month 6 The safety profile observed in this study is consistent with the previously reported results of itacitinib combined with corticosteroids The most common adverse reactions were thrombocytopenia (34.9% in the itacitinib group, 34.7% in the placebo group) and anemia (29.8% in the itacitinib group, 25.0% in the placebo group) Incyte will inform the investigator of the results and work with them to close the study appropriately in the best interests of each patient Data from the study will be presented to the forthcoming scientific conference "The results of this study are disappointing," said Steven Stein, chief medical officer of Incyte However, we are still committed to building on the success of jakafi's reach project, which shows positive results in steroid refractory aGVHD In addition, we will continue to study the role of JAK inhibition in chronic graft-versus-host disease (cGVHD) and preventive therapy, with the aim of developing new therapies for patients with this debilitating and often fatal disease " GVHD is an immune disease caused by the anti host reaction of allogeneic hematopoietic stem cell transplantation In this case, the implanted cells initiate an immune response and attack the recipient's organs GVHD can be divided into two types (acute and chronic), which can affect multiple organ systems The most common organs involved are skin, gastrointestinal tract and liver Clinically, most patients are treated with glucocorticoid, which is a kind of steroid drug Long-term use will lead to serious health complications Patients with steroid refractory acute GVHD can develop into severe diseases, with a one-year mortality rate of about 70% In May 2019, Incyte's drug jakafi (ruxolitinib) was approved by the US FDA for the treatment of steroid refractory acute graft-versus-host disease (aGVHD) in children and adults aged 12 and over It is worth mentioning that jakafi is the first drug approved by FDA to treat the indication, and has been granted breakthrough drug qualification, orphan drug qualification and priority review by FDA Jakafi is the first oral inhibitor of Janus kinase 1 and Janus kinase 2 (Jak1 / JAK2) It has been approved for three indications in the United States The other two indications are: (1) treatment of adult patients with erythrocytosis (PV) who have inadequate or intolerant response to thioglycosuria; (2) treatment of adult patients with high-risk myelofibrosis (MF), including primary MF, MF after PV, and primary thrombocytosis After MF Jakafi is sold in the United States by Incyte and Novartis is sold under the name of jakavi in markets outside the United States Itcitinib (incb39110), a new, powerful and selective inhibitor of Jak1, was found by Incyte It is currently being evaluated in a number of clinical studies for the first-line treatment of acute and chronic graft versus host disease (GVHD) In December 2018, Cinda biology and Incyte company reached a strategic cooperation and exclusive licensing agreement to promote the clinical development and commercialization of single or combined treatment of three drugs (itacitinib, parsaclsib, pemigatinib) in mainland China, Hong Kong, Macao and Taiwan According to the provisions of the cooperation agreement, Cinda bio will pay the down payment of US $40 million to Incyte first, and US $20 million will be paid to Incyte as the second cash payment after Xinda bio first submits the new drug application in China in 2019 In addition, Incyte will be eligible for potential development milestone payments of up to $129 million and potential commercial milestone payments of up to $202.5 million Further financial details of the cooperation were not disclosed Source of original text: infinite announcements results of phase 3 study of itanitinib in patients with treatment Na ï ve acute grant versus host release