FDA Approves Home Administration for Omacetaxine Mepesuccinate

Meir Wetzler, MD

The FDA has approved a home administration route for the subcutaneous injection omacetaxine mepesuccinate (Synribo) in patients with chronic or accelerated phase chronic myeloid leukemia (CML) who are resistant or intolerant to treatment with tyrosine kinase inhibitors.

A Medication Guide and Instructions for Use was approved along with the new indication for omacetaxine mepesuccinate, a protein synthesis inhibitor that was originally granted an accelerated approval in October 2012. A full approval was granted in February 2014 based on long-term analysis from two single-arm phase II trials. These same data supported the new home administration indication. Teva Pharmaceuticals, the company manufacturing the drug, plans to launch a specialty pharmacy support program that facilitates home administration in the middle of 2014.

“It had been necessary for adults living with chronic or accelerated phase CML who are prescribed Synribo to travel to their doctor’s office twice a day for two weeks, which can be extremely burdensome and inconvenient to both patients and their caregivers,” Meir Wetzler, MD, chief of the Leukemia Section at Roswell Park Cancer Institute, said in a release. “Now, physicians can decide if their patients are candidates for self administration, and if so, provide their patients with guidance on how to properly administer reconstituted Synribo in the home.”

The final ≥24-month follow-up analysis from the clinical studies was presented at the 2013 ASH Annual Meeting. This efficacy analysis included 76 patients with chronic phase (CP) and 35 patients with accelerated phase (AP) CML. The primary endpoints were major cytogenetic response (MCyR) for CP and major hematologic response (MaHR) for AP.

The median treatment duration after a 29.5 month follow-up was 7.5 months for patients with CP CML. After a median 14.3-month follow-up, the median treatment duration was 1.6 months for patients with AP CML. Responses were similar at the longer follow-up to original assessments in the blinded data monitoring committee review. In the original assessment, 18% of CP patients achieved a MCyR for a 12.5-month median, and 14% of AP patients achieved a MaHR for a median 4.7-month duration.

For the secondary endpoint of progression-free survival, the median was 9.6 months for patients with CP CML and 3.6 months for AP patients. Based on the ≥24-month update, median OS was extended from 33.9 months to 40.3 months for CP patients and remained 14.3 months for patients with AP CML.

The most common adverse events (>20%) were thrombocytopenia, anemia, neutropenia, diarrhea, nausea, fatigue, asthenia, injection site reaction, pyrexia, infection, and lymphopenia for CP and AP patients. Grade 3/4 hematologic toxicities for CP and AP patients were thrombocytopenia (CP 85%, AP 88%), neutropenia (CP 81%, AP 70%), leukopenia (CP 76%, AP 60%), and anemia (CP 60%, AP 78%).

“As an oncology nurse practitioner who has treated CML patients for nearly 20 years, I’m thrilled to see this unique therapy become available for home administration,” Sandra Corbin, CRNP at Calvert Hematology and Oncology, said in a release. “Patients may initially express concern at the thought of self-injecting—but with training and support, most can become skilled at administering the subcutaneous injections.”

The recommended dose and schedule for the subcutaneous omacetaxine mepesuccinate injection is 1.25 mg/m² twice daily for 14 days of a 28-day cycle for the induction phase and 1.25mg/m² twice daily for 7 days of a 28-day cycle for maintenance.