FDA Pipeline: Designations and Reviews in Myelofibrosis, Myelodysplastic Syndromes, Biliary Tract Cancer, and T-Cell Receptor Therapy


Recently, the U.S. Food and Drug Administration (FDA) granted Fast Track designation for momelotinib in myelofibrosis, granted Priority Review to a biologics license application for luspatercept in myelodyslastic syndromes and beta-thalassemia, granted Orphan Drug designation for a new chemical entity in biliary tract cancer, cleared an investigational new drug application for a T-cell receptor therapy trial, and granted clearance to a device designed to improve quality of colonoscopies when bowel preparation has been insufficient.

Momelotinib Granted Fast Track Designation for Intermediate/High-Risk Myelofibrosis

The FDA granted Fast Track designation to momelotinib, a JAK1, JAK2, and ACVR1 inhibitor, for the treatment of patients with intermediate-risk/high-risk myelofibrosis who have previously received a JAK inhibitor.

The randomized, double-blind phase III MOMENTUM trial, which will further investigate momelotinib in this setting, is set to launch later in 2019. It is designed to enroll 180 patients with myelofibrosis who are symptomatic and anemic and have been treated previously with a JAK inhibitor.

Patients will be randomly assigned 2:1 to receive either momelotinib or danazol. Danazol has been selected as an appropriate treatment comparator given its use to ameliorate anemia in myelofibrosis patients as recommended by National Comprehensive Cancer Network® and European Society for Medical Oncology guidelines. After 24 weeks of treatment, patients on danazol will be allowed to crossover to receive momelotinib.

The primary endpoint of the trial is the total symptom score response rate of momelotinib compared to danazol at week 24. Key secondary endpoints include the transfusion-independence rate at week 24, splenic response rate at week 24, duration of total symptom score response to week 48, transfusion-dependence response rate, various measures of cumulative transfusion burden, and patient-reported outcome measures of fatigue and physical function. 

More than 1,200 patients have received momelotinib since clinical studies began in 2009. This population includes more than 800 patients treated for myelofibrosis.

Luspatercept Biologics License Application Accepted for Myelodysplastic Syndromes and Beta-Thalassemia

The FDA accepted a biologics license application (BLA) for luspatercept, an investigational erythroid maturation agent, for the treatment of adult patients with very low–risk to intermediate-risk myelodysplastic syndromes (MDS)-associated anemia who have ring sideroblasts and require red blood cell transfusions, as well as for the treatment of adult patients with beta-thalassemia–associated anemia who require red blood cell transfusions. The FDA has granted Priority Review to this BLA for the evaluation of the beta-thalassemia indication and set a Prescription Drug User Fee Act (PDUFA) date of December 4, 2019. The FDA has also set a PDUFA date of April 4, 2020, for the evaluation of the MDS indication.

The safety and efficacy results provided in the application are from the phase III MEDALIST and BELIEVE trials, which evaluated the ability of luspatercept to effectively treat the anemia associated with MDS and beta-thalassemia, respectively. MEDALIST and BELIEVE were both presented at the 2018 American Society of Hematology Annual Meeting & Exposition, where MEDALIST was included in the plenary session.

Orphan Drug Designation for NUC-1031 in Biliary Tract Cancer

The FDA granted Orphan Drug designation for the investigational drug NUC-103 in the treatment of biliary tract cancer. NUC-103 is a new chemical entity.

“We are pleased to have received Orphan Drug designation from the FDA for NUC-103 in biliary tract cancer,” said Hugh Griffith, NuCana’s Founder and Chief Executive Officer, in a press release. “There is a high unmet need for patients suffering from this cancer type.  Our phase Ib study of NUC-103 combined with cisplatin showed an approximate doubling of the response rate expected with the standard of care, gemcitabine plus cisplatin, with several patients achieving significant reductions in their tumor volume as well as further tumor shrinkage over time. We believe NUC-103 represents a potential significant advance in biliary tract cancer and we remain on track to open our global phase III study in combination with cisplatin as a front-line treatment for patients with advanced biliary tract cancer in 2019.”

Investigational New Drug Application Cleared for Sleeping Beauty TCR T-Cell Therapy Trial

The investigational new drug application submitted by the National Cancer Institute (NCI) has received clearance from the FDA for a clinical trial in solid tumors to evaluate T-cell receptor (TCR) T-cell therapy utilizing the Sleeping Beauty platform.

Ziopharm and the NCI are partnered in a cooperative research and development agreement under the direction of Steven Rosenberg, MD, PhD, Chief of the Surgery Branch of the NCI, supporting clinical work to evaluate a nonviral approach to manufacturing TCR T-cell therapy with the Sleeping Beauty platform that targets solid tumors. With this approach, T cells can be genetically modified to express multiple, tumor-specific TCRs.

Clearance for Pure-Vu Colonoscopy Device

The FDA granted 510(k) clearance for the second generation Pure-Vu colonoscopy device.

The original Pure-Vu device was designed to attach to standard and slim colonoscopes to deliver a mixture of water and air to remove debris when patients hadn’t completed their bowel preparation prior to colonoscopy. Pure-Vu GEN2 has been designed to improve the mobility and setup logistics of the system and enhance navigation through the colon, while retaining all the same cleansing functionality as the system’s first generation.

The initial launch will focus on the inpatient colonoscopy market, where challenges with insufficient bowel preparation can slow diagnosis, diminish quality of care, and add significant costs to hospital systems.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.