Real-world data in drug development strategies for orphan drugs: Tafasitamab in B-cell lymphoma, a case study for an approval based on a single-arm combination trial.

Tafasitamab (TAF) plus lenalidomide (LEN) is a novel treatment option for patients with relapsed/refractory diffuse large B-cell lymphoma (rrDLBCL) who are not eligible for autologous stem cell transplantation. The initial US/EU approvals for TAF represent precedents because this is the first time that approval of a novel combination therapy was granted based on a pivotal single-arm trial (SAT). Matching real-world data (RWD) helped to disentangle the contribution of individual agents. In this review, we present the TAF development strategy, the prospective incorporation of RWD within the clinical development plan, the corresponding regulatory hurdles of this strategy, and the prior regulatory actions for other cancer drugs that previously incorporated RWD and propensity score matching in EU and US regulatory submissions. We also outline how RWD could further advance and impact orphan drug development.

Storage and transport of reconstituted omacetaxine mepesuccinate: Considerations for home administration.

Purpose Omacetaxine mepesuccinate ("omacetaxine") is approved by the US Food and Drug Administration for the treatment of adult patients with chronic- or accelerated-phase chronic myeloid leukemia with resistance and/or intolerance to two or more tyrosine kinase inhibitors. In May 2014, the US Food and Drug Administration approved revisions to the packaging information that included directions for home administration of reconstituted omacetaxine by patients or caregivers using syringes filled at a healthcare facility. We developed recommendations for the transport, storage, and spill-clean procedure of reconstituted omacetaxine for home and clinic administration. Methods We conducted chemical stability and microbial growth studies of reconstituted omacetaxine solution stored in vials and syringes at room temperature or refrigerated for various durations. Several shipping configurations were tested in simulated transport conditions to evaluate their ability to contain solution leakage and maintain product quality during distribution. In addition, we evaluated cleaning products and procedures for their effectiveness in removing residual omacetaxine from household surfaces after mock spills. Results Reconstituted omacetaxine showed limited degradation when refrigerated for 14 days in vials and syringes, and no microbial growth was observed for 12 days after intentional inoculation. In shipping studies, the configurations maintained prepared syringes within the recommended storage temperature range throughout transport and could contain leaks if spills occurred. In the event of an accidental spill in a home environment, effective cleaning can be achieved using household cleaning products and defined procedures. Conclusion These data provide important information regarding the safe transportation and administration of reconstituted omacetaxine in the home and clinic.