FDA grants tentative approval to new cabozantinib capsule formulation

The FDA has granted tentative approval to cabozantinib (OMCAZIO) capsules, a novel alternate-salt formulation of cabozantinib developed under the 505(b)(2) regulatory pathway, according to an announcement from Handa Pharmaceuticals.¹

If granted final approval, the product would provide an alternative oral formulation of cabozantinib for several previously approved indications, including as a monotherapy and in combination with nivolumab (Opdivo) for advanced renal cell carcinoma (RCC), as well as for hepatocellular carcinoma (HCC) and advanced extra-pancreatic neuroendocrine tumors (epNETs).

Tentative approval is generally issued when an application satisfies FDA requirements for safety, efficacy, and manufacturing quality but cannot receive final approval because of existing marketing exclusivity or patent protections associated with the reference product.

"Tentative approval marks an important regulatory milestone for Handa,” said Bill Liu, chairman and CEO of Handa Pharmaceuticals, in the news release from the company.¹ “We developed OMCAZIO with the goal of providing an alternative oral cabozantinib formulation that may offer greater flexibility for patients and health care providers. We are continuing our commercial readiness activities and look forward to making OMCAZIO available to patients following FDA final approval."

Bioequivalence findings

Unlike the currently marketed CABOMETYX tablets, OMCAZIO is formulated as an alternate salt designed to improve drug absorption. According to the Handa, pharmacokinetic studies demonstrated bioequivalence to CABOMETYX at lower milligram doses and found no clinically significant food effect.

Based on the bioequivalence findings, the proposed prescribing information includes recommendations for converting patients between CABOMETYX tablets and OMCAZIO capsules. Patients receiving CABOMETYX 60 mg once daily would transition to OMCAZIO 34.5 mg once daily, those receiving 40 mg once daily would transition to 23 mg once daily, and those receiving 20 mg once daily would transition to 11.5 mg once daily.

Data on cabozantinib in RCC

Cabozantinib was initially approved by the FDA in April 2016 for the treatment of patients with advanced RCC who had previously received antiangiogenic therapy. The indication was expanded in December 2017 to include first-line treatment of advanced RCC based on findings from the phase 2 CABOSUN trial, in which cabozantinib significantly improved progression-free survival compared with sunitinib (Sutent) in patients with previously untreated intermediate- or poor-risk disease (HR, 0.48; 95% CI, 0.31-0.74; P = .0008).

Subsequently, the phase 3 CheckMate 9ER trial showed that cabozantinib combined with nivolumab significantly improved progression-free survival, overall survival, and objective response rates vs sunitinib, leading to regulatory approval of the combination as a first-line treatment for advanced RCC in January 2021.³

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