Development

Raziel's RZL-012 meets Phase III endpoints for submental fat reduction, paving China NDA path

Raziel's RZL-012 meets Phase III endpoints for submental fat reduction, paving China NDA path

A pivotal 480-patient Phase III trial of utenpanium chloride (RZL-012) has met all primary and secondary efficacy and safety endpoints in submental fat (fat located under the chin) reduction after a single treatment cycle, according to results announced by Israel-based Raziel Therapeutics and China-based Fosun Pharma. The companies plan to submit a New Drug Application to China's National Medical Products Administration by year-end 2026.

The randomized, placebo-controlled trial enrolled 360 patients in the active arm and 120 in the placebo arm. Efficacy was assessed 84 days after a single treatment cycle, with the primary responder rate showing approximately a 30-percentage-point advantage over placebo. Exact absolute rates and p-values were not disclosed. The trial was conducted through Fosun Pharma's affiliate JuveStar.

RZL-012 is a synthetic small-molecule injectable that destroys adipocyte membranes subcutaneously, leading to permanent fat cell elimination at the injection site. The compound is administered in one to two injection sessions by trained physicians. Unlike AbbVie's Kybella (deoxycholic acid injection) — the only FDA-approved injectable drug for submental fat reduction, which requires up to six treatment sessions spaced at least one month apart — RZL-012's pivotal data were generated after a single cycle, a potential convenience differentiator that the companies said supports its commercial positioning.

The Phase III trial initiation in China was announced in March 2025, with JuveStar responsible for conducting the study and Raziel supplying drug substance and finished product. The positive readout now clears the path for an NDA filing in what Raziel describes as the first of several planned aesthetic indications for the compound. Fosun is separately preparing a follow-on trial evaluating RZL-012 in body contouring — a broader focal fat reduction indication where no injectable drug currently holds approval in any major market.

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Deoxycholic acid, marketed as Kybella in the US and Belkyra in Europe, has faced adoption constraints linked to its multi-session burden and injection-site reaction profile, including swelling, bruising, and rare cases of marginal mandibular nerve injury. Caliway Biopharmaceuticals' CBL-514, a competing injectable lipolytic agent, received FDA clearance for a Phase III trial in abdominal subcutaneous fat in July 2025 but is not targeting the submental indication.

A strategic collaboration with South Korea's 365mc, announced in July 2025, is intended to support Phase III development and commercialization in Korea, with 365mc also making a strategic investment in the company. A US Phase III program remains in preparation, with Phase II completed with the FDA.

The China NDA, if submitted on schedule, would position RZL-012 for a potential 2027 launch in a market where Kybella has limited penetration and where Fosun's distribution infrastructure provides a commercial pathway. Full numerical data from the pivotal trial have not been disclosed; the companies said detailed results will be presented at an upcoming scientific conference.


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