dm+d

Unassigned

New Medicines

EpjevyMyelofibrosis

Information

Epjevy
New molecular entity
CTI Biopharma
CTI BioPharma

Development and Regulatory status

Filing withdrawn
Filing withdrawn
Pre-registration (Filed)
Yes
Yes
Jun 21US FDA grants Priority Review with a PDUFA action date 30/11/21 [27].
Mar 21CTI BioPharma complete rolling submission of NDA to FDA [26].
Oct 20CTI BioPharma initiate rolling submission of NDA to FDA [25].
Sep 20BioPharma announce plans to submit NDA to FDA for accelerated approval of pacritinib for myelofibrosis with severe thrombocytopenia. The application will be based on available data from completed PIII PERSIST-1 and PERSIST-2 trials [24].

Feb 19: CTI BioPharma notified the EMA on 7th Feb 2019 that it wished to withdraw the marketing authorisation application (MAA) for pacritinib (proposed trade name Epjevy). The CHMP had reviewed the data presented by the company, and its answers to questions raised, and had come to the provisional opinion that the drug could not have been approved: although it reduced spleen size in patients, it had not been shown to reduce symptoms - one of the main objectives of treatment. Additionally, the most appropriate dose had not yet been determined. In its letter withdrawing the application, the company stated that it could not generate the additional data required within the procedural time frame [23].


Jul 17: CTI announces that the EMA has validated and accepted a re-submitted Marketing Authorisation Application for pacritinib for the treatment of patients with myelofibrosis who have thrombocytopenia. [22]. If there are no major questions raised during the assessment, this implies a CHMP opinion early in 2018 and if positive, EC authorisation in Spring 2018.


Oct 16: CTI terminates the licence agreement with Baxalta and takes back full worldwide rights [21].


Mar 17: EU filing withdrawn because there was not enough time in the current application procedure to provide new data from a second main study with Enpaxiq. The company said that it intends to integrate the new data from the study into its current dossier before approaching EMA to discuss a new application [19].


Jun 16: Listed as filed in CHMP list of medicines under evaluation [15].


May 16: CTI Biopharma is preparing for release of top-line results from the PERSIST-2 PIII trial in Q3 16 [16].


Mar 16: FDA releases the clinical hold on certain investigator-sponsored trials that were evaluating pacritinib and informed the company that emergency requests may be submitted for individual patient expanded access. Also FDA expressed interest in submitting a request under a Single Patient IND (SPI) program, for patients who were receiving benefit from pacritinib treatment at the time the clinical hold to resume pacritinib treatment on a case-by-case basis [16].


Feb 16: the FDA´s partial hold has been upgraded to a full clinical hold on trials, thus all patients currently taking pacritinib must discontinue it and no new patients should be started on it. As a result, the New Drug Application has been withdrawn [14].


Feb 16: CTI BioPharma announces that the FDA has put a partial hold on clinical studies being carried out with pacritinib, due to excess mortality and other adverse effects in the active treatment group compared to control in the PERSIST-1 study. The excess was most evident during crossover to pacritinib and the hold will apply until the significance of the excess has been clarified; during this period, no new patients should be enrolled to trials, patients must not be started on pacritinib as initial or crossover treatment, and patients not deriving benefit after 30 weeks of pacritinib treatment should stop using it. Otherwise, those patients currently taking the drug may continue using it [13].


Nov 15: As part of the US licence application, CTI BioPharma and Baxalta are seeking accelerated approval and priority review for pacritinib for treatment of patients with intermediate and high-risk myelofibrosis with low platelet counts of less than 50,000 per microliter. If approved, pacritinib would be the first JAK2 inhibitor approved for treatment of patients with myelofibrosis with platelet counts


Nov 15: CTI BioPharma begins a rolling FDA submission for pacritinib. The company expects to complete its application by end of 2015 [12].


Sep 15: CTI BioPharma announce plan to submit NDA in the fourth quarter of 2015 [11].


Aug 14: Pacritinib has been granted Fast Track designation in the US for the treatment of intermediate and high risk myelofibrosis, including but not limited to patients with disease-related thrombocytopenia, patients experiencing treatment-emergent thrombocytopenia on other JAK2 therapy and patients intolerant to or whose symptoms are sub-optimally managed on other JAK2 therapy [8].


Nov 13: CTI BioPharma and Baxter enter into a worldwide license agreement. CTI BioPharma and Baxter will jointly commercialise pacritinib in the US while Baxter has exclusive commercialisation rights for all indications outside the US [9].


Jan 13: PIII study starts [3].


Orphan drug status in the EU and US [2].


S Bio has announced plans to commence global, Phase III, double-blind, placebo-controlled trials [1]

Category

Tyrosine kinase inhibitor with dual activity against Janus Associated Kinase 2 (JAK2) and FMS-like tyrosine kinase 3 (FLT3)
In the EU, 3 people in 100,000 has primary fibromyosis, equivalent to around 15,000 people.
Myelofibrosis
Oral

Further information

Yes
Suspended

Trial or other data

Mar 17: Results of PERSIST-1 (n=327) published in The Lancet Haematology [20].


Aug 16: CTI announces preliminary results from the PERSIST-2 trial which met one of the co-primary endpoints, showing a statistically significant response rate in spleen volume reduction in patients with myelofibrosis treated with pacritinib vs. Jakavi. But it did however fail to meet its other co-primary endpoint, of greater than 50% reduction in total symptom score. Most common treatment emergent adverse events for pacritinib were generally manageable diarrhea, nausea and vomiting. Incidence of cardiac and bleeding adverse events (all grades and grade 3-4 including deaths) were similar across the arms, with overall mortality rates comparable between arms. Additional data from ongoing analyses along with top-line results from PERSIST-2 will be posted at an upcoming scientific meeting [17].


Mar 15: BioPharma and Baxter announce positive top-line results for the primary endpoint from PERSIST-1, with a statistically significant response rate (p = 0.0003) in spleen volume reduction in patients with myelofibrosis when compared to BAT, including patients with severe or life-threatening thrombocytopenia. There was also a significant difference among patients with platelet counts of less than 100,000 per microliter and less than 50,000 per microliter, both subgroups that were stratified at randomization. The safety profile in the PERSIST-1 trial was consistent with prior Phase 2 trials. While the most common treatment emergent adverse events were diarrhoea, nausea and vomiting, the incidence of grade 3 events was lower than observed in Phase 2 trials. No grade 4 gastrointestinal adverse events were reported. Three patients discontinued therapy and nine patients required dose reduction for diarrhoea. Preliminary analysis suggests that very few patients discontinued treatment while on pacritinib or required a dose reduction due to treatment-related anemia or thrombocytopenia. Additional data from ongoing analyses along with top-line results from PERSIST-1 will be submitted for presentation at an upcoming scientific meeting [9].


Feb 14: NCT02055781 is a PIII randomized controlled study of pacritinib vs best available therapy (BAT) in 300 patients with thrombocytopenia and primary myelofibrosis, post-polycythemia vera myelofibrosis, or post-essential thrombocythemia myelofibrosis. The primary hypothesis is that treatment with either once or twice-daily pacritinib, vs BAT, results in a greater proportion of patients achieving from baseline to week 24 (1) a ≥ 35% reduction in spleen volume and (2) a ≥ 50% reduction in total symptom score measured by the Myeloproliferative Neoplasm Symptom Assessment Form 2.0. BAT may include ruxolitinib, other approved JAK2 inhibitors, hydroxyurea, glucocorticoids, erythropoietic agents, immunomodulatory agents, mercaptopurine, danazol, interferons, cytarabine, melphalan and may also include no treatment and symptom-directed treatment without myelofibrosis-specific treatment. The study starts Dec 13 and is due to complete Aug 18 (primary data collection Aug 15) [7].


Nov 13: Baxter and Cell Therapeutics have entered into an exclusive worldwide licensing agreement to develop and commercialise pacritinib [6]


Oct 13: Company has reached agreement with the FDA on a Special Protocol Assessment (SPA) for the planned PIII study, PERSIST-2. The randomized, open-label, multi-center trial will evaluate pacritinib (200 or 400mg daily) vs best available therapy, including approved JAK2 inhibitors such as ruxolitinib, in 300 patients with myelofibrosis whose platelet counts are


PERSIST-1 (NCT01773187) is due to complete Aug 17, with collection of primary outcome data by Aug 14 [4].


Jan 13: Enrollment in the PIII PERSIST-1 (or PAC325) study has started. The study will evaluate the safety and efficacy of pacritinib (400mg once daily) vs best available therapy, excluding JAK inhibitors, in 270 patients with primary myelofibrosis, post-polycythemia vera myelofibrosis or post-essential thrombocythemia myelofibrosis. The study will not exclude patients with low platelet counts as PII studies suggest pacritinib does not cause thrombocytopenia or anaemia. The primary endpoint will be the percentage of patients achieving a ≥ 35% reduction in spleen volume measured by MRI or CT at 24 weeks of treatment. The trial will be conducted in Europe, Australia and the IS. One of the principal investigators is Claire Harrison, Consultant Haematologist at Guy´s and St. Thomas. A second PIII trial is planned to evaluate pacritinib vs best available therapy, including JAK inhibitors, in patients with myelofibrosis whose platelet counts are


Apr 12: Cell Therapeutics has entered into an agreement to acquire pacritinib [2]


In 2011, while reviewing PII results, S*Bio outlined the following safety issues;17 patients (50%) discontinued, 8 because of nausea, sepsis, increased bilirubin, subdural haematoma, allergic reaction, GI bleed, 2 due to thrombocytopenia, 5 for disease progression and 2 for lack of response. Of the AEs leading to discontinuation, only increased bilirubin, allergic reaction and intermittent nausea were considered possibly drug related. Ten patients required dose reduction for adverse events [2]


Oct 11: S Bio has announced plans to commence global, Phase III, double-blind, placebo-controlled trials of pacritinib (SB1518), for the treatment of myelofibrosis (MF). The primary objective is to compare the efficacy of pacritinib vs. placebo in achieving clinically significant reduction in spleen size in MF patients with splenomegaly. Secondary outcomes of both studies include patient-reported change in the most bothersome symptom identified at baseline, duration of response, as well as overall survival. The trials will enrol up to 500 MF patients [1].

Evidence based evaluations