RESUMEN
BACKGROUND: Fremanezumab is a humanized monoclonal antibody against calcitonin gene-related peptide for subcutaneous use to suppress migraine attacks. A phase 3 study was conducted to investigate the safety of autoinjector (AI)-assisted self-injection of fremanezumab 225 mg. RESEARCH DESIGN AND METHODS: The multicenter, open-label study involving 71 patients with migraine was conducted between June 2020 and November 2020 at ten institutions in Japan. The study consisted of a 4-week (28-day) screening period and an 8-week (57-day) treatment period. According to the investigator's instructions, all patients successfully performed self-injection for 4 weeks at the institutional site and at home and maintained eDiaries of their headaches. The primary endpoint was safety of the drug based on treatment-emergent adverse events (TEAEs). RESULTS: Treatment-emergent adverse events were more frequent after at-home injection than after at-site injection, but they were mainly injection site reactions and mostly mild. The safety profile was comparable, raising no concerns compared with what has been reported in previous studies. Both migraine days and headache days were decreased considerably. CONCLUSIONS: Overall, AI-assisted, at-home self-injection of fremanezumab was found to be generally safe and well-tolerated. This injection strategy is considered clinically meaningful in view of improved utility of and adherence to the drug.
RESUMEN
Roseophilin is a unique metabolite containing two pyrrole and one furan ring and is structurally related to tripyrrole antibiotics, prodigiosins. Each homologous gene in the roseophilin producer Streptomyces griseoviridis was amplified by PCR using primers designed from the prodigiosin-biosynthesis genes redH, redM, and redW. A search for prodigiosins produced by S. griseoviridis resulted in the isolation of a new prodigiosin designated prodigiosin R1 (1). The molecular formula of 1 was established as C27H37N3O by high-resolution FABMS. The structure of 1 was elucidated by NMR spectroscopic analysis including COSY, HMQC, HMBC, and NOESY. Prodigiosin R1 (1) is a new member of the prodigiosin family possessing a cyclic alkyl side chain.
Asunto(s)
Prodigiosina , Streptomyces/química , Streptomyces/genética , Compuestos Heterocíclicos con 3 Anillos/química , Compuestos Heterocíclicos con 3 Anillos/aislamiento & purificación , Datos de Secuencia Molecular , Estructura Molecular , Resonancia Magnética Nuclear Biomolecular , Prodigiosina/análogos & derivados , Prodigiosina/biosíntesis , Prodigiosina/química , Pirroles/química , Pirroles/aislamiento & purificación , Streptomyces/metabolismoRESUMEN
Streptomyces griseoviridis 2464-S5 produces prodigiosin R1, a tripyrrole antibiotic, and roseophilin, a structurally related compound containing two pyrrole and one furan rings. A gene cluster for the biosynthesis of a prodigiosin was identified in S. griseoviridis. The cluster consisted of 24 open reading frames, including 21 genes (rphD-rphZ) homologous to prodigiosin biosynthesis genes in the red cluster in Streptomyces coelicolor A3(2). The expression of rphN in S. coelicolor lacking redN restored the production of prodigiosin.