The first new bone marrow fibrosis drug in nearly a decade! Hundred-time Meishi Shiguibao JAK2 inhibitor Inrebic EU approved: will become a clinical new standard of care!

2021 // -- BMS recently announced that the European Commission (EC) has granted full market approval to Inrebic, a highly selective JAK2 inhibitor for primary bone marrow fibrosis, true erythrocytosis, In adult patients with primary plate enlargement bone marrow fibrosis, treatment of disease-related spleen enlargement (enlargement of the spleen) or symptoms, including patients who have not received JAK inhibitors (jaK inhibitors for initial treatment) and patients who have received ruxolitinib (Jakavi/Jakafi, Rusotini, Novartic/Incyte oral JAK1/JAK2 inhibitors) (JAK inhibitors).
It is worth noting that Inrebic is the first new treatment for bone marrow fibrosis in Europe in nearly 10 years, and will also be the first daily oral therapy to significantly reduce spleen volume and symptom burden in patients with ruxolitinib treatment failure, inability to treat ruxolitinib or jak inhibitor primary treatment.
nearly a decade, there has been no treatment for patients with progressing bone marrow fibrosis with ruxolitinib, a rare bone marrow disease characterized by weak symptoms and swelling of the spleen.
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).
approved through the FDA's priority vetting process and was previously granted orphan drug eligibility.
addition, Inrebic was approved by Canada.
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, which is available oral twice a day.
note that Inrebic's product prescription information is accompanied by a black-box warning of the risks 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 thiamin (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.
this approval, based on the results of the JAKARTA study and the JAKARTA2 study. Dr Claire Harrison, professor of hematology at Guy's and St Thomas' NHS Trust in London, said:
Myel fibrosis is a serious bone marrow disease that usually debilitates people and has only one approved treatment in the last decade.
clinical data show that in patients who are progressing in ruxolitinib or have not yet been treated with JAK inhibitors, Inrebic treatment results in a clinically significant reduction in spleen volume and symptoms.
in the EU, about one in every 100,000 people is diagnosed with bone marrow fibrosis each year, and today's approval provides an important new option for patients who still desperately need new treatments.
"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.
the EU approval, 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 conducted in 97 patients with primary or secondary bone marrow fibrosis who had previously been treated with Jakafi to assess the efficacy and safety of Inrebic (starting dose 400 mg).
results showed that Inrebic treatment showed clinically significant response rates.
in patients with intentional therapy (ITT, n-97), 31% of patients had their spleen volume reduced by 35% at the end of the 6th cycle ≥ treatment.
97 patients, 79 (81%) met the narrower jakafi resistance or insatiability criteria.
in this queue, the proportion of patients with a reduction in spleen volume by ≥35% at the end of the sixth week was 30% (95% 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 remission rates of ≥50% was 27%.
fedratinib molecular structure (Photo: Wikipedia) Inrebic's active pharmaceutical ingredient is Fedratinib, an oral kinase inhibitor, 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 transducers and transcription activators (STAT3/5) proteins, inhibits cell proliferation, and induces apoptosis 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 European Commission for Inrebic® For Adult Patients with Diagnosed and Previously Treated Myelofibrosis<!--/ewebeditor:page->