Date: 2017-02-20
Type of information: Withdrawal of a market application in the EU
Product name: Enpaxiq®
Compound: pacritinib
Therapeutic area: Cancer - Oncology
Action mechanism: kinase inhibitor/ tyrosine kinase inhibitor. Pacritinib is an oral tyrosine kinase inhibitor with dual activity against JAK2 and FLT3. The JAK family of enzymes is a central component in signal transduction pathways, which are critical to normal blood cell growth and development, as well as inflammatory cytokine expression and immune responses. Mutations in these kinases have been shown to be directly related to the development of a variety of blood-related cancers, including myeloproliferative neoplasms, leukemia and lymphoma. Pacritinib may offer an advantage over other JAK inhibitors through effective treatment of symptoms while having less treatment-emergent thrombocytopenia and anemia than has been seen in currently approved and in-development JAK inhibitors.
CTI BioPharma and Baxalta are parties to a worldwide license agreement to develop and commercialize pacritinib. CTI BioPharma and Baxalta will jointly commercialize pacritinib in the U.S. while Baxalta has exclusive commercialization rights for all indications outside the U.S.
Company: CTI BioPharma - previously known as Cell Therapeutics (USA - WA) Baxalta (USA - IL)
Disease: myelofibrosis
Latest news:
- • On February 20, 2017, CTI BioPharma officially notified the Committee for Medicinal Products for Human Use (CHMP) that it wishes to withdraw its application for a marketing authorisation for Enpaxiq®, for treating patients with an enlarged spleen or other symptoms of myelofibrosis. a disorder in which scar tissue builds up in the bone marrow where blood cells are produced.
- The application was withdrawn after the CHMP had evaluated the initial documentation provided by the company and formulated a list of questions. At the time of the withdrawal of application, the CHMP was of the provisional opinion that Enpaxiq® could not have been approved for myelofibrosis.
The Committee had a number of concerns: the reduction in spleen size, the main measure of effectiveness in the study, appeared to be lower with Enpaxiq® than with another medicine of its class, with no improvement in symptom scores; the incidence of low blood platelet levels (which can cause bleeding) was higher in patients treated with Enpaxiq®; and a higher number of deaths occurred in patients taking Enpaxiq® than in those receiving best available therapy, including deaths due to bleeding and effects on the heart.
Furthermore, the CHMP noted that more information was needed about the starting materials used in the manufacture of Enpaxiq® and how it acts on certain target proteins in the body. Given these concerns, the Committee was of the opinion that the benefits of Enpaxiq® had not been shown to outweigh its risks.
- CTI BioPharma presented data from a main study in 327 patients with myelofibrosis that looked at thenumber of patients whose spleen size reduced by at least 35% after 24 weeks of treatment. The study compared Enpaxiq® with ‘best available therapy’, which included treatments that do not act on JAK proteins such as hydroxyurea or supportive care.
The company stated in its letter to the Agency that it was withdrawing the application 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.
- • On January 5, 2016, CTI BioPharma and Baxalta announced the completion of the rolling submission of the New Drug Application (NDA) to the FDA for pacritinib, an investigational oral kinase inhibitor with specificity for JAK2, FLT3, IRAK1 and CSF1R. CTI BioPharma and Baxalta are requesting U.S. marketing approval of pacritinib for the treatment of patients with intermediate and high-risk myelofibrosis with low platelet counts of less than 50,000 per microliter (<50,000/µL). The Companies are seeking accelerated approval and have requested a Priority Review of the application.
- The NDA includes data from the PERSIST-1 Phase 3 trial - as well as data from Phase 1 and 2 studies of pacritinib. Submission of an NDA after a single Phase 3 trial under accelerated approval, instead of waiting to complete two Phase 3 trials, could potentially reduce time to market by up to 14 months. In August 2014 (see below) , pacritinib was granted Fast Track designation by the FDA for the treatment of intermediate and high-risk myelofibrosis including, but not limited to, patients with disease-related thrombocytopenia (low platelet counts); patients experiencing treatment emergent thrombocytopenia on another JAK2 therapy; or patients who are intolerant to or whose symptoms are not well controlled (or sub-optimally managed) on another JAK2 therapy.
- • On November 23, 2015, CTI BioPharma announced the initiation of its rolling new drug application (NDA) to the FDA for pacritinib, an investigational oral kinase inhibitor with specificity for JAK2, FLT3, IRAK1 and CSF1R. As part of the application, CTI BioPharma and its partner, Baxalta, are seeking accelerated approval and priority review for pacritinib for the treatment of patients with intermediate and high-risk myelofibrosis with low platelet counts of less than 50,000 per microliter (<50,000/uL). If approved for the requested indication, pacritinib would be the first JAK2 inhibitor approved for the treatment of patients with myelofibrosis with platelet counts of less than 50,000/uL - a specific patient population for which there are currently no approved drugs. The rolling NDA allows completed portions of an NDA to be submitted and reviewed by the FDA on an ongoing basis. CTI BioPharma and Baxalta plan to complete the submission before the end of 2015. The submission includes data from the PERSIST-1 Phase 3 trial - as well as data from Phase 1 and 2 studies of pacritinib. Submission of an NDA after a single Phase 3 trial under accelerated approval, instead of waiting to complete two Phase 3 trials, could potentially reduce time to market by up to 14 months. In August 2014, pacritinib was granted Fast Track designation by the FDA for the treatment of intermediate and high-risk myelofibrosis including, but not limited to, patients with disease-related thrombocytopenia (low platelet counts); patients experiencing treatment emergent thrombocytopenia on another JAK2 therapy; or patients who are intolerant to or whose symptoms are not well controlled (or sub-optimally managed) on another JAK2 therapy. CTI BioPharma and Baxalta are parties to a worldwide license agreement to develop and commercialize pacritinib. CTI BioPharma and Baxalta will jointly commercialize pacritinib in the U.S. while Baxalta has exclusive commercialization rights for all indications outside the U.S.
- • On August 7, 2014,CTI BioPharma announced that pacritinib has been granted Fast Track designation by the FDA 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 or patients who are intolerant to or whose symptoms are sub-optimally managed on other JAK2 therapy. The drug candidate is currently being evaluated in two Phase 3 clinical trials, known as the PERSIST program, for patients with myelofibrosis. Last month CTI BioPharma has completed recruitment in the PERSIST-1 of pacritinib. The primary endpoint is the percentage of patients achieving a greater than or equal to 35 percent reduction in spleen volume measured by MRI or CT from baseline to 24 weeks of treatment.
- In March 2014, CTI announced the initiation of the PERSIST-2 trial, which will evaluate pacritinib compared to best available therapy, including approved JAK2 inhibitors that are dosed according to product label, in patients with myelofibrosis whose platelet counts are less than or equal to 100,000/uL. The trial is designed to enroll up to 300 patients in North America, Europe, Australia and New Zealand. In October 2013, CTI reached agreement with the FDA on a Special Protocol Assessment (SPA) for the PERSIST-2 trial, which is a written agreement between CTI and the FDA regarding the planned design, endpoints and statistical analysis approach of the trial to be used in support of a potential NDA submission. Under the SPA, the agreed upon co-primary endpoints are the percentage of patients achieving a 35 percent or greater reduction in spleen volume measured by MRI or CT scan from baseline to 24 weeks of treatment and the percentage of patients achieving a Total Symptom Score (TSS) reduction of 50 percent or greater using six key symptoms as measured by the modified Myeloproliferative Neoplasm Symptom Assessment (MPN-SAF TSS 2.0) diary from baseline to 24 weeks.
Patents:
Submission of marketing authorization application USA :
Submission of marketing authorization application UE:
Withdrawal of marketing authorization application USA:
Withdrawal of marketing authorization application UE: 2017-02-20
US authorization:
UE authorization:
Favourable opinion UE:
Favourable opinion USA:
Orphan status USA:
Orphan status UE: 2010-08-25
Pediatric exclusivit _USA:
Pediatric exclusivity UE:
OTC status:
Other news:
Is general: Yes
