RZL-012, a New Fat Dissolving Molecule, Tested in Dercum's Disease Patients

Gueta, Racheli; Blaugrund, Eran; Bloomenfeld, Alon; Herbst, Karen L.

doi:10.1097/dss.0000000000002989

Cited by 3 publications

(2 citation statements)

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“…RZL-012 is a clinical stage product being developed for fat-related disorders such as Dercum's disease and aesthetic applications. 5 , 16 The compound is administered by a single injection session into subcutaneous fat deposits, resulting in reduction of fat tissue volume. This phase 2b study met the primary endpoint, namely the proportion of patients who had at least a 1-grade improvement in C-CAT (Day 84 vs baseline) showed statistically significant differences between the high-dose RZL-012 and placebo treatment groups ( P = .0011).…”

Section: Discussionmentioning

confidence: 99%

Efficacy and Safety of Tapencarium (RZL-012) in Submental Fat Reduction

Shridharani¹,

Dayan

Biesman³

et al. 2023

Aesthetic Surgery Journal

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Background Tapencarium (RZL-012) (5-(3.6-dibromo-9H-carbazol-9-yl)-N, N, N-trimethylpentan-1-aminium chloride) is a novel injectable synthetic molecule with cytolytic properties, capable of reducing subcutaneous fat volume. Objectives This three-arm, randomized, double blind, placebo-controlled phase 2b study determined the safety and efficacy of low and high dose RZL-012 versus placebo on submental fat (SMF) reduction. Methods Subjects (n = 151, aged 18-65 years) with excess SMF received a single treatment session of RZL-012 or placebo into the submental area, after which they were monitored for 84 days. SMF was assessed at baseline and after dosing using newly developed scales, namely the Clinician Chin Assessment Tool (C-CAT) and Subject Chin Assessment Tool (S-CAT). SMF was also assessed by magnetic resonance imaging (MRI) at screening and day 84 after treatment. Results The proportion of subjects who had a 1-grade or 2-grade improvement in C-CAT and/or S-CAT on Day 84 vs. baseline was significantly higher in the high dose RZL-012 group versus the placebo group (p < 0.002). The relative percent reduction in MRI measured SMF volume (Day 84 vs. screening) was significantly greater in the high dose RZL-012 group vs. the low dose RZL-012 or the placebo group (P < 0.0001). Local injection-site reactions were the most common AEs. Conclusions A single administration of RZL-012 into SMF resulted in significant improvement in submental appearance as assessed by clinicians, subjects and MRI. From a safety perspective, there were no serious AEs nor any clinically significant changes in vital signs or laboratory tests over the course of the study.

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Section: Discussionmentioning

confidence: 99%

Efficacy and Safety of Tapencarium (RZL-012) in Submental Fat Reduction

Shridharani¹,

Dayan

Biesman³

et al. 2023

Aesthetic Surgery Journal

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“…To address localized fat deposits in a single treatment session, Raziel Therapeutics developed a novel cytolytic drug, tapencarium (RZL-012, 5-(3,6-dibromo-9H-carbazol-9-yl)- N , N , N -trimethylpentan-1-aminium chloride), which has shown promise in reducing fat deposits in the submental area and in patients with Dercum's disease. 5 , 6 Injection of RZL-012 into fat tissue disrupts cell membrane integrity, subsequently killing fat cells, after which the treated area goes through the normal inflammatory and wound-healing process, with complete clearance of dead fat tissue seen at 84 days after injection in animal studies. 7 …”

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confidence: 99%

Tapencarium (RZL-012) for Flank Fat Reduction: A Proof-of-Concept Study

Shridharani,

Kennedy,

Gueta

et al. 2023

Aesthetic Surgery Journal Open Forum

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Background RZL-012 is a novel cytolytic drug that has shown promise in reducing localized fat deposits in a single treatment session. Objectives To assess the safety and efficacy of injecting RZL-012 to the flanks. Methods A double-blind, placebo-controlled proof-of-concept study randomized 12 subjects to receive RZL-012 injections in 1 flank and placebo injections in the contralateral flank. After 12 weeks of follow-up, subjects could receive RZL-012 in the placebo-treated flank and be followed for 12 weeks in the open-label phase. Results At 12 weeks, Investigator Global Aesthetic Improvement Scale assessments showed improvement for 90.9% of RZL-012-treated flanks and 0% of placebo-treated flanks (p < 0.0001), 81.8% of subjects were satisfied with the RZL-012-treated flanks and 9.1% with the placebo-treated flanks (p = 0.0019), and volume reduction measured on 3-dimensional images was a mean 37.27 mL, which was significantly greater than placebo (p = 0.0052). The product was well tolerated, with no clinically significant trends in laboratory values, electrocardiograms, or vital signs. Pharmacokinetic analyses demonstrated that RZL-012 is quickly absorbed, reaches maximum concentration in approximately 1.67 hours, and has a half-life of 9.1 hours. The mean maximal concentration of RZL-012 found in the blood was <1 µg/mL. Conclusions RZL-012 is a promising option for injectable fat reduction of the flanks in a single treatment session. The drug was well tolerated in this small subject population, with no concerning safety signals, and it had indications of efficacy. Further research is needed in large phase 2 studies with robust efficacy measurements to confirm these early findings.

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Patent Highlights August–September 2021

Mucke¹

2022

Pharm. Pat. Anal.

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RZL-012, a New Fat Dissolving Molecule, Tested in Dercum's Disease Patients

Cited by 3 publications

References 4 publications

Efficacy and Safety of Tapencarium (RZL-012) in Submental Fat Reduction

Efficacy and Safety of Tapencarium (RZL-012) in Submental Fat Reduction

Tapencarium (RZL-012) for Flank Fat Reduction: A Proof-of-Concept Study

Patent Highlights August–September 2021

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