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39807711000001105

New Medicines

InrebicPrimary myelofibrosis, post polycythaemia vera myelofibrosis or post essential thrombocythaemia myelofibrosis - treatment of disease-related splenomegaly or symptoms in adults who are JAK inhibitor naïve or have been treated with ruxolitinib

Information

Inrebic
New molecular entity
Bristol-Myers Squibb
Bristol-Myers Squibb

Development and Regulatory status

Launched
Approved (Licensed)
Launched
June 2021
Yes
Yes
Jun 21Launched in UK. Price for 120 x 100mg caps = £6,119.68 [22].
Apr 21MHRA grants orphan drug status to fedratinib. As the MHRA grants this status at the time of authorisation, it can be assumed that the MHRA has licensed fedratinib but at present no further details are available [20].
Dec 20Recommended for EU approval by CHMP - the full indication is "for the treatment of disease-related splenomegaly or symptoms in adult patients with primary myelofibrosis, post polycythaemia vera myelofibrosis or post essential thrombocythaemia myelofibrosis who are JAK inhibitor naïve or who have been treated with ruxolitinib" [17]
Nov 20BMS reports revenues from sales of Inrebic in the US, $13 million in Q3 and $40 million in the 9 months to end of Q3 20 [18].
Jan 20Currently pre-registration in EU [16].
Aug 19FDA approved Inrebic for treatment of adult patients with intermediate-2 or high-risk primary or secondary (post-polycythemia vera or post-essential thrombocythemia) myelofibrosis. [16]
Mar 19Accepted for priority review in US, with a target action date of 3/9/19 [13].
Jul 18Celgene plans to file fedratinib before the end of 2018 [12].
Mar 18Celgene is now developing fedratinib. PIII development has resumed in EU & US [10].
Oct 17FDA lifts hold on clinical trials of fedratinib after reviewing additional data provided by Sanofi. One of the factors taken into consideration are they very limited therapeutic options available for these patients so benefit may outweigh risk in some. Re-investment into the product may lead to further development by Impact Biosciences. [9]
Nov 13Sanofi discontinues development of fedratinib, following reports of cases consistent with Wernicke’s encephalopathy in patients participating in studies. The US FDA had told Sanofi to put all fedratinib trials on clinical hold while the company thoroughly investigated the cases [8].
May 13Filings are being planned [7].
Dec 11Orphan drug status in the EU [2] and the US [3].
Sep 11PIII study to start Oct 11 [1].

Category

Selective inhibitor of Janus kinase 2 (JAK2) and FLT-3 tyrosine kinase
In the EU, primary myelofibrosis affects ~0.3 in 10,000 people (15,000 people), post-essential thrombocythaemia myelofibrosis affects < 0.01 in 10,000 people (<500 people) and post-polycythaemia vera myelofibrosis affects < 0.15 in 10,000 people (<8,000 people).
Primary myelofibrosis, post polycythaemia vera myelofibrosis or post essential thrombocythaemia myelofibrosis - treatment of disease-related splenomegaly or symptoms in adults who are JAK inhibitor naïve or have been treated with ruxolitinib
Oral

Further information

Yes

Trial or other data

Dec 19Updated efficacy data from JAKARTA and JAKARTA-2 presented at 61st Annual Meeting and Exposition of the American Society of Hematology [15].
Oct 17JAKARTA-2 trial meets its primary endpoint [11].
Apr 14PII JAKARTA-2 trial investigating efficacy and tolerability of fedratinib in patients with intermediate-2 or high-risk myelofibrosis, following polycythaemia vera or essential thrombocythaemia, who had previously been treated with another JAK2 inhibitor, ruxolitinib completes (NCT01523171). The follow-on study enrolled 97 patients in Austria, Belgium, Canada, France, Germany, Italy, Netherlands, Spain, United Kingdom, and the US [11].
May 13The pivotal study, JAKARTA, examining the selective JAK2 inhibitor SAR302503 for myelofibrosis (MF), met its primary endpoint in both dose groups. Results will be published at a forthcoming conference. [6]
Jan 13Recruitment to the PIII JAKARTA study is complete and headline results are expected Q2 2013 [5].
Dec 12New data from A PII study reported. The open label, randomized dose-ranging study evaluated the once-daily oral doses of 300mg, 400mg and 500mg of SAR302503. Spleen volume at the end of cycle three assessed by MRI with independent central review (primary endpoint) was reduced vs baseline by a mean of 30% (n=10), 33% (n=10) and 42% (n=11), in each group, respectively. The proportion of patients who achieved a ≥35% reduction in spleen volume by MRI was 30%, 50% and 63.6% in each group, respectively. The proportion of patients who achieved ≥50% reduction in the Myeloproliferative Neoplasm Symptom Assessment Form (MPN-SAF) score, a sum of six key constitutional symptoms (night sweats, itching, abdominal discomfort, abdominal pain, bone pain, early satiety), was similar in all groups (44-50%). The most common serious (grade 3-4) haematologic adverse event was anaemia ( 33%, 30% and 55%, respectively). Rates of grade 3-4 thrombocytopenia were 20%, 0% and 9%, respectively. The most common grade 3-4 non-haematological events were diarrhoea (10%, 20%, 0%), nausea (10%, 10%, 0%) and vomiting (10%, 10%, 0%). Two patients in the 300mg group discontinued treatment due to an adverse event (grade 3 anaemia, grade 4 transaminase elevation) [4].
Sep 11NCT01437787 (JAKARTA) - A PIII, multicenter, randomized, double-blind study of SAR302503 in 225 patients with intermediate-2 or high-risk primary myelofibrosis, post-polycythemia vera myelofibrosis, or post-essential thrombocythemia myelofibrosis with splenomegaly. The primary objective is to evaluate the efficacy of daily oral doses of 400 or 500mg of SAR302503 vs placebo in the reduction of spleen volume as determined by MRI (or CT scan in patients with contraindications for MRI). The primary outcome is response rate, defined as the proportion of patients who have a ≥35% reduction in volume of spleen size at the end of cycle 6, and confirmed 4 weeks thereafter (time frame: 6 months). Patients who continue to benefit clinically will be allowed to remain on SAR302503 or placebo beyond the 6-month treatment period until the occurrence of disease progression or unacceptable toxicity. The study will start Oct 11 and is due to complete Jan 16 (date for primary outcome data collection Feb 13) [1].

Evidence based evaluations