Genovate Biotechnology Co., Ltd. announced its plans to submit a New Drug Application (NDA) with the United States Food and Drug Administration (US FDA) for PMR, an investigational once daily extended-release form of cilostazol for the treatment of Intermittent Claudication, in the second half of 2025. In the written responses to the pre-NDA meeting package, the FDA confirmed that the clinical studies conducted are sufficient to support the submission of a marketing application under the 505(b)(2) regulatory pathway. The key study in the submission package, GBL23-001 (NCT06167265), is a randomized, fully replicate crossover study designed to evaluate the bioequivalence and within-subject variability between PMR 145 mg once daily and the immediate-release tablet of cilostazol 100 mg twice daily.

This study is expected to be completed in mid-2024, and the top-line results have shown that the primary endpoints of the study were achieved, and the decision to submit the application was made following the successful outcome of study GBL23-001. Furthermore, Genovate has been improving the PMR formulation and its manufacturing processes in order to address additional FDA comments. All clinical study and manufacturing data are expected to be included in the final submission package.

PMR (Cilostazol Extended-Release Tablets) PMR, a novel extended-release (ER) formulation of cilostazol, was designed to reduce the concentration-dependent side effects associated with immediate-release (IR) tablet form of cilostazal. Cilostazol is currently available in IR tablet form at 50 and 100 mg strengths administered twice daily. The IR formulation of cilostazal, marketed as Pletal®?

in the US (Pletaal®? in Taiwan and other Asian countries), was first available in Japan in 1988 for the treatment of peripheral arterial diseases and the prevention of recurrence of cerebral infarction and later approved by the US FDA in 1999 for the treatment of intermittent claudication (IC). Cilostazol is a specific PDE III inhibitor that can cause reduced platelet aggregation and increased vasodilatation.

Cilostazol showed good efficacy in preventing secondary strokes, notably reducing the rates of ischaemic stroke recurrence. Nevertheless, the results from eight placebo-controlled clinical trials indicated that 15.4% of patients withdrawn from cilostazol treatment were as a result of adverse reactions. Headache, palpitations, and diarrhea were the most frequently reported adverse reactions among these patients.

These adverse reactions were attributable to the peak concentration of cilostazol. Genovate is developing an ER tablet form of cilostrazol, PMR, to be administered once daily aiming to improve adherence and to reduce the side effects associated with the high peak-to-trough variation of the concentration of cilostazal IR.