The first new bone marrow fibrosis drug in nearly a decade! Hundred-time Meishi Shiguibao JAK2 inhibitor Inrebic EU is about to be approved, has been listed in the United States!

December 15, 2020 / -- BMS recently announced that the European Medicines Agency (EMA) Committee on Human Pharmaceutical Products (CHMP) has issued a positive review recommending approval of the highly selective JAK2 inhibitor Inrebic (Fedratinib) for primary myeloma, true red blood cell disease Adult patients with post-marrow fibrosis, primary plate plate enlargement bone marrow fibrosis, treated for disease-related spleen enlargement (enlargement of the spleen) or symptoms, including patients who had not received JAK inhibitors (jaK inhibitors for initial treatment) and patients who had received ruxolitinib (Jakavi/Jakafi, Rusotini, Novarian/Incyte oral JAK1/JAK2 inhibitors) (JAK inhibitors).
chMP's comments will now be submitted to the European Commission, which usually makes a final review decision within two months.
If approved, Inrebic will be the first new treatment for bone marrow fibrosis in Europe in nearly a decade, and the first daily oral therapy to significantly reduce the volume and symptom burden of the spleen in patients with failed ruxolitinib treatment or the initial treatment of JAK inhibitors.
Inrebic was acquired by Shishi Shiguibao for $74 billion.
August 2019, Inrebic was approved by the FDA for the treatment of adult patients with secondary or secondary bone marrow fibrosis of medium-risk-2 and high-risk (intermediate-2/high-risk) (after erythrocyte augmentation or after primary plate small plate augmentation).
inrebic was approved through the FDA's priority vetting process and previously qualified for orphan drugs.
bone marrow fibrosis is a serious bone marrow disease that disrupts normal blood cell production in the body.
approval, making Inrebic the first new bone marrow fibrosis drug approved by the FDA in nearly a decade, will provide patients with a new daily oral treatment option.
2011, Novarma/Incyte's JAK1/JAK2 inhibitor Jakafi (ruxolitinib, Rusotini) was approved by the FDA as the first drug to treat bone marrow fibrosis.
It is important to note that in the United States, Inrebic's product prescription information is accompanied by a black-box warning of the risk of severe and fatal encephalopathy (brain injury or malfuncation), including Wernicke's.
in clinical studies, 1.3% of patients treated with Inrebic (n=8/608) developed severe encephalopathy, of which 0.16% (n=1/608) died.
encephalopathy is a neuro-emergency caused by a deficiency of thiamine (vitamin B1).
all patients should periodically test for thiamine levels before and during Inrebic treatment.
patients with thiamine deficiency are unable to initiate treatment;
if encephalopathy is suspected, inrebic treatment should be stopped immediately and extraintestinal thiamine should be activated.
monitoring until symptoms disappear or improve and thiamine levels normalize. "For nearly a decade, there has been no treatment for patients with myeloid fibrosis who are progressing with ruxolitinib, a rare bone marrow disease characterized by weakness and swelling of the spleen," said Diane McDowell, M.D., vice president of global medical affairs at
Centennia Mercer Hematology.
CHMP's positive comments on Inrebic reinforce our commitment to improving standards of care for patients with resocced blood disorders, and we look forward to the European Commission's decision to approve it.
"bone marrow fibrosis-spleen swelling (Photo: oncohemakey.com) Inrebic's development project consists of several studies (including Phase III clinical study JAKARTA and Phase II clinical study JAKARTA2), in which 608 patients received at least one treatment (dose range: 30mg to 800mg), of which 459 patients with bone marrow fibrosis were treated, including 97 previously treated with Jakafi.
positive review of CHMP, based on the results of the JAKARTA study and the JAKARTA2 study.
JAKARTA was a randomized, placebo-controlled study that assessed the efficacy and safety of 2 doses (400 mg and 500 mg) of Inrebic relative to placebo in 289 patients who had not previously been treated with JAK inhibitors.
results showed that 37% of patients in the Inrebic 400mg dose group (n=35/96) had a reduction in spleen volume compared to baseline ≥35 per cent and 40 per cent (n=36/89) after the end of the 6th cycle of treatment The overall symptom score of bone marrow fibrosis was 50% better than the baseline≥ and the placebo group was 1% (n-1/96) and 9% (n-7/81), respectively, with statistically significant differences (average p<0.0001).
JAKARTA2 is a one-arm, open-label study that evaluated the efficacy and safety of Inrebic (starting dose 400 mg) in 97 patients with primary or secondary bone marrow fibrosis who had previously been treated with Jakafi.
results showed that Inrebic therapy showed clinically significant response rates.
in patients with intentional therapy (ITT, n-97), 31% of patients had a 35% reduction in spleen volume after the end of the 6th cycle ≥ treatment.
97 patients, 79 (81%) met the narrower jakafi resistance or insatiability criteria.
in this queue, the spleen volume was reduced by ≥35 percent at the end of the sixth week to 30 percent (95 percent CI: 21,42), consistent with the response rate observed in the ITT population.
addition, in the ITT group (95% CI:18,37) and in patients included in the narrow standard analysis (95% CI:17,39), the proportion of patients with symptom relief rate ≥50% was 27%.
fedratinib molecular structure (Photo: Wikipedia) Inrebic's active pharmaceutical ingredient is fedratinib, an oral kinase inhibitor that is active against wild and mutant-activated Janus-related kinase 2 (JAK2) and FMS-like tyrosine kinase 3 (FLT3).
is a SELECTIVE inhibitor of JAK2, which has a higher inhibitory effect on JAK2 than family members JAK1, JAK3 and TYK2.
activation of JAK2 is associated with bone marrow-boosting tumors (MPNs), including bone marrow fibrosis and true red blood cell growth.
In cell models that express mutations that activate JAK2 or FLT3, fedratinib reduces phosphorylation of signal transductors and transcription activators (STAT3/5) proteins, inhibits cell proliferation, and induces apoptosis cell death.
In mice with JAK2V617F-driven bone marrow-boosting disease, fedratinib blocked STAT3/5 phosphate, improved survival, and improved disease-related symptoms, including leukocyte reduction, red blood cell ratio, spleen enlargement, and fibrosis.
Origin: Bristol Myers Squibb Receives Positive CHMP Opinion for Inrebic ® For Adult Patients New with Diagnosed and Previously Treated Myelofibrosis<!--/ewebeditor:page->