Ruxolitinib

Articles · Lactation Safety Information · New Medicines ·
703779004

Articles

Lactation Safety Information

No published evidence of safety
Serious adverse effects reported in adults
22nd September 2020

New Medicines

Jakavi (EU), Jakafi (US) · Acute graft versus host disease (GvHD)

Information

Jakavi (EU), Jakafi (US)
Licence extension / variation
Novartis
Incyte

Development and Regulatory status

Phase III Clinical Trials
Phase III Clinical Trials
Launched
Yes
Mar 20 · EU filing planned for 2021 [14].
May 19 · US FDA announced approval of ruxolitinib for treatment of steroid-refractory acute GVHD in pts aged 12 years and older.[12]
Dec 18 · Planned filing date (presumably EU) is 2020 [11].
Oct 18 · US FDA grants Priority Review for ruxolitinib as a treatment for patients with acute GVHD who have had an inadequate response to corticosteroids. The submission is based on data from the REACH1 study [10].
Jun 18 · Following positive data from REACH 1, Incyte announced plans to file a sNDA for the approval of ruxolitinib to treat steroid-refractory acute GVHD with the US FDA during Q3 2018.[8]
Dec 17 · Filings now expected 2020 [7].
Mar 17 · Novartis plans to file in 2019 [6].
Jun 16 · Incyte announce that the FDA has granted Breakthrough Therapy designation for ruxolitinib for treatment of patients with acute graft versus host disease (GVHD) [1].

Category

JAK1 and JAK2 inhibitor
Incidence of acute GVHD after bone marrow and stem cell transplant varies widely, between 10% and 80% depending on risk factors. It is a prominent cause of death in recipients of such transplants [3].
Acute graft versus host disease (GvHD)
Oral

Trial or other data

Nov 20 · Acute GVHD is a major cause of morbidity and mortality after bone marrow or stem-cell transplantation. There are a number of accepted treatments, including systemic corticosteroids, calcineurin inhibitors, and extracorporeal photopheresis, however there are few reported randomised controlled trials and evidence for many of the treatments used is limited [4, 5]. This first-in-class JAK1/JAK2 inhibitor is the first FDA-approved treatment for this indication [12].
Jul 20 · Incyte announces PIII REACH3 study meets primary endpoint [16].
Apr 20 · The REACH2 RCT (n=309) found that ruxolitinib therapy led to significant improvements in overall response at day 28 compared to control group (62% vs. 39%; OR 2.64; 95% CI, 1.65 to 4.22; p<0.001) with a higher incidence of thrombocytopenia, the most frequent toxic effect [15].
Oct 19 · PIII REACH2 trial meets primary endpoint of improved overall response rate (ORR) at day 28 with ruxolitinib vs best available therapy [13].
Jun 18 · Data for pivotal PIII studies in steroid-refractory acute GVHD (REACH2) and steroid-refractory chronic GVHD (REACH3) are expected in 2019.[8]
Jun 18 · The REACH 1 trial, evaluating ruxolitinib (Jakafi®) + corticosteroids for treatment of steroid-refractory acute GVHD met its primary endpoint. REACH 1 is a single-cohort, pivotal PII study (NCT02953678) which demonstrated an overall response rate (ORR) of 55% (n=39/71) at Day 28 and the best overall response rate (BORR), i.e. the no of pts achieving a response at any time point during the study, was 73% (n=52/71). The most common treatment-emergent adverse events of any grade were anemia (61%), thrombocytopenia (61%) and neutropenia (56%).[8]
Feb 17 · PIII REACH2 study to evaluate the safety and efficacy of ruxolitinib compared to Best Available Therapy in patients with corticosteroid-refractory acute graft vs. host disease after allogeneic stem cell transplantation (NCT02913261). 308 patients aged 12 years and older will be recruited from Europe (including UK) and other countries around the world, except the US. Primary outcome is overall response rate; collection of these data due to complete June 19 [9].
Jun 16 · Incyte intend to initiate a pivotal PIII study during the second half of 2016 [2].

Evidence based evaluations

Jakavi (EU), Jakafi (US) · Chronic graft versus host disease (GvHD)

Information

Jakavi (EU), Jakafi (US)
Licence extension / variation
Novartis
Incyte

Development and Regulatory status

Phase III Clinical Trials
Phase III Clinical Trials
Phase III Clinical Trials

Category

JAK1 and JAK2 inhibitor
This is an important entity and a major cause of late non-relapse death after haematopoietic cell transplantation. It is recommended that all patients be scored initially at three months post-transplant and every three months thereafter if they are diagnosed with GvHD. There are two aspects to the scoring, resulting in a classification of mild, moderate and severe chronic GvHD [1]. Incidence rates range from 6 to 80%, depending upon presence of risk factors and diagnostic criteria used [2].
Chronic graft versus host disease (GvHD)
Oral

Evidence based evaluations

Atopic dermatitis

Information

New formulation
Incyte
Incyte

Development and Regulatory status

Phase III Clinical Trials
Phase III Clinical Trials
Phase III Clinical Trials

Category

JAK inhibitor
In adults, population studies report an overall prevalence of 2-18%, in children around 20% [2].
Atopic dermatitis
Topical

Alopecia areata, moderate-to-severe

Information

New formulation
Concert Pharmaceuticals
Concert Pharmaceuticals

Development and Regulatory status

None
None
Phase III Clinical Trials

Category

Selective inhibitor of Janus kinase 1 and Janus kinase-2 inhibitors (JAK 1 and 2). Deuterated formulation of ruxolitinib alters its human pharmacokinetics which may enhance its use as a treatment for alopecia areata.
In the UK, alopecia areata is estimated to affect about 15 in 10,000 people. [1]
Alopecia areata, moderate-to-severe
Topical