Peginterferon alfa-2b (Xiamen Amoytop)

Pegbing® (peginterferon alfa‐2b), a pegylated interferon‐alpha, is approved for the treatment of chronic hepatitis B (CHB) and C. One of its adverse effects is platelet (PLT) suppression. It is currently being repurposed for the treatment of essential thrombocythemia (ET), a rare myeloproliferative disorder characterized by abnormally elevated PLT levels and associated with significant unmet clinical needs. The drug repositioning strategy of Pegbing® from CHB to ET aims to accelerate development and reduce costs. Through the application of pharmacometrics, the existing data from CHB patients were leveraged to inform dose selection and clinical trial design for ET patients. The pharmacokinetic/pharmacodynamic (PK/PD) model of Pegbing® for PLT and white blood cell (WBC) inhibition was established using data from a phase II trial conducted in CHB patients who received Pegbing®, and validated with data from a phase III trial. The PK/PD relationship was extrapolated to ET patients by adjusting baseline PLT and WBC levels using real‐world data from ET patients receiving off‐label treatment with Pegbing®. According to the parameter distribution and correlation from the extrapolated PK/PD relationship, 1,000 virtual ET patients were generated to form an in silico clinical trial, revealing that baseline PLT and WBC levels were key factors for hematologic response. Pegbing® 180 μg is expected to be an appropriate dose for future development, with an overall complete hematologic response rate of 62.3%. A higher maintenance dose may be required in patients with severe ET. Moreover, this study provides a valuable reference for drug repositioning between two indications with significant differences.

Craniopharyngiomas account for approximately 1.2–4% of all CNS tumors. They are typically treated with a combination of surgical resection and focal radiotherapy. Unfortunately, treatment can lead to permanent deleterious effects on behavior, learning, and endocrine function.

The Pediatric Brain Tumor Consortium performed a multicenter phase 2 study in children and young adults with unresectable or recurrent craniopharyngioma (PBTC-039). Between December 2013 and November 2017, nineteen patients (median age at enrollment, 13.1 y; range, 2–25 y) were enrolled in one of 2 strata: patients previously treated with surgery alone (stratum 1) or who received radiation (stratum 2).

Eighteen eligible patients (8 male, 10 female) were treated with weekly subcutaneous pegylated interferon alpha-2b for up to 18 courses (108 wk). Therapy was well tolerated with no grade 4 or 5 toxicities. 2 of the 7 eligible patients (28.6%) in stratum 1 had a partial response, but only one response was sustained for more than 3 months. None of the 11 stratum 2 patients had an objective radiographic response, although median progression-free survival was 19.5 months.

Pegylated interferon alpha-2b treatment, in lieu of or following radiotherapy, was well tolerated in children and young adults with recurrent craniopharyngiomas. Although objective responses were limited, progression-free survival results are encouraging, warranting further studies.