A snapshot of noteworthy recent developments in the patent literature of relevance to pharmaceutical and medical research and development.WO/2021/152390 Compositions for the treatment of angiolipoma Inventors: Bloomenfeld A, Gueta R, Blaugrund E Assignees: Raziel Therapeutics Ltd. (Rehovot, Israel) In contrast to lipomas that contain only fat tissue, angiolipomas have a considerable vascular component, and a thin ?brous capsule with incomplete ?brous septa extending into the lesion, dividing it into lobules of different size.They are histologically benign and usually subcutaneous, but can occur almost anywhere including the CNS 1, and can invade surrounding structures. Treatment of angiolipomas is usually by surgery or, in some cases, injection of corticosteroids into the cell mass. Although their ?brous membranes make angiolipomas relatively resistant to fat-reducing agents, the inventors provide such compounds herein. These are substituted carbazoles carrying a C1-9alkyl chain at the nitrogen atom, and a terminal quaternary amino or phosphonium group. They are to be formulated for intratumoral injection, in daily doses of 5–40 mg and in volumes of 1–2 ml per subcutaneous tumor.An open-label phase IIa clinical trial (NCT04229030) was conducted with one of the compounds (RZL-012; 5- (3,6-dibromo-9H-carbazol-9-yl)-N,N,N-trimethylpentan-1-aminium chloride) in patients with nodular Dercum’s disease (adiposis dolorosa) 2. Up to four lipomas from each of the six patients were injected once with up to 20 mg RZL-012 per lipoma and up to 40 mg RZL-012 per patient. Tumor height and pain were signi?cantly reduced after 28 and 56 days. Preclinical studies in pigs have established the mechanism: RZL-012 destroys adipocytes by directly disrupting cell membrane integrity. Replacement of dead fat tissue by ?brotic tissue enables healing and causes contraction of the injected area 3. A phase IIb trial for obesity with submental fat (NCT04867434) commenced in June 2021.
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