Reformulation of Abiraterone Effective in Metastatic Prostate Cancer

A new formulation of abiraterone acetate called TAVT-45 demonstrated therapeutic equivalence to Zytiga, the currently approved formulation, in patients with metastatic castration-resistant prostate cancer (mCRPC) and metastatic castration-sensitive prostate cancer (mCSPC), according to a press release from Tavanta Therapeutics.¹

The phase 3 registrational TAVT45C02 trial (NCT04887506) showed equivalent testosterone level at day 9 and 10 and no statistical difference in the decrease of prostate-specific antigen (PSA) levels in patients between TAVT-45, which is formulated as granules for oral suspension, and abiraterone in tablet form.

"The positive results from the TAVT45C02 trial demonstrate that TAVT-45 may provide an easy-to-swallow alternative to Zytiga, benefitting many patients with dysphagia or difficulty swallowing large tablets," Andreas Maetzel, MD, PhD, chief medical officer of Tavanta Therapeutics, said in a statement. "Approximately 20% to 30% of [patients with] cancer, including many patients with prostate cancer, have difficulty swallowing pills and capsules. We believe these patients may benefit from an alternate formulation like TAVT-45 that would allow them to take their much-needed medications in an easier-to-take formulation."

Current formulations of abiraterone acetate given in large tablets are difficult for some patients to swallow and must be taken on an empty stomach. TAVT-45 is a granule formulation of abiraterone acetate that can be reconstituted in water or juice and consumed as an oral suspension. It may also increase the bioavailability of abiraterone and allow a lower dose to be effective.

The global, multicenter open-label phase 3 trial randomly assigned approximately 107 patients with mCRPC or mCSPC to receive either 250 mg of TAVT-45 as a sachet twice daily without respect to food versus 500 mg abiraterone tablets twice daily at least 1 hour before or 2 hours after a meal. Both arms received 5 mg prednisone once or twice daily depending on the disease setting.

The primary end point was blood serum testosterone levels averaged over day 9 and 10 of treatment to determine pharmacodynamics of the 2 formulations. Secondary end points included the percent of patients with a PSA decrease of 50% or greater from baseline over 84 days and additional pharmacokinetics measures.

In addition to meeting the primary end point and the PSA secondary end point, it was reported that the safety profile of TAVT-45 was in line with that of abiraterone in tablet form.

“It is encouraging to see a familiar efficacy and safety profile for TAVT-45, which is consistent with data established for abiraterone acetate as a standard of care in the treatment of metastatic prostate cancer,” Kenneth M. Kernen, MD, a study investigator and partner in the Michigan Institute of Urology, said in a press release. “The positive results from this clinical study further support and validate the use of TAVT-45 as a novel, oral, easy-to-drink formulation of abiraterone acetate. As a physician, this would be a welcome potential treatment alternative that may also help patients adhere to their medication regimens and may ultimately improve clinical outcomes.”

The results of the study will be presented at an upcoming medical meeting and will be submitted for publication.

“Tavanta intends to submit our New Drug Application to the [FDA], while also evaluating strategic options for the commercialization of TAVT-45,” said Lynne Powell, CEO of Tavanta Therapeutics.

_Reference:

_{1. Tavanta Therapeutics Announces positive top-line results from pivotal phase 3 trial of TAVT-45 for the treatment of metastatic prostate cancer. Tavanta Therapeutics. January 5, 2023. Accessed January 6, 2023. https://bit.ly/3VWn3f4}