Tricida appeal to FDA denied

 Tricida, Inc. (Nasdaq: TCDA), a pharmaceutical company focused on the development and commercialization of its investigational drug candidate, veverimer, a non-absorbed, orally-administered polymer designed to treat metabolic acidosis in patients with chronic kidney disease (CKD), today provided an update on its U.S. Food and Drug Administration (FDA) interactions.

Tricida has received an Appeal Denied Letter (ADL), from the Office of New Drugs (OND) of the FDA in response to its Formal Dispute Resolution Request (FDRR) submitted in December 2020. While the FDRR was focused on whether the magnitude and durability of serum bicarbonate change seen in the TRCA-301/TRCA-301E trial is reasonably likely to predict clinical benefit in the treatment of metabolic acidosis in patients with CKD, the OND’s decision additionally addressed other deficiencies identified in the Complete Response Letter (CRL), which Tricida received in August 2020. The additional issues addressed included the reliability of the data from the TRCA-301/TRCA-301E trial due to the disproportionate impact of data from a single high-enrolling clinical site on the trial’s results and the applicability of the trial results to the U.S. patient population given that the majority of the subjects in the study were enrolled in sites outside of the United States or were in regions that the FDA does not consider “U.S.-like,” such as Eastern Europe.

In the ADL, the OND acknowledged that the TRCA-301/TRCA-301E trial met its serum bicarbonate endpoints with statistical significance but concluded that the extent of serum bicarbonate increase observed in the TRCA-301/TRCA-301E trial is not reasonably likely to provide a discernible reduction in CKD progression. The OND also concluded that the confirmatory trial, VALOR-CKD, is underpowered to detect the effect size (13%) predicted by the original Tangri model (also known as the Predictive MA Model) based upon the placebo-subtracted mean treatment effect observed in the TRCA-301/TRCA-301E trial.

The OND also provided feedback on other concerns that are particularly relevant in an NDA supported by a single registrational trial. The OND noted concerns around the trial results being strongly influenced by a single site, and the majority of sites for the TRCA-301/TRCA-301E trial being in Eastern Europe, where differences in patient management, including concomitant medications and diet, might affect the treatment response to veverimer and raise a concern of the applicability to a U.S. patient population. The FDA did not raise any concerns related to its completed inspection of the highest-enrolling clinical trial site and there was no FDA Form 483 issued. Also, while the OND did not suggest that there was a specific unblinding issue in the TRCA-301/TRCA-301E trial, the OND noted concerns around adequate blinding and that, while the measures in place to protect the study blind in the TRCA-301/TRCA-301E trial were reasonable, they may not have optimally protected the blind.

Although the ADL provides greater clarity on the potential path for approval of veverimer through the Accelerated Approval Program, Tricida believes the timeline to meet the requirements for accelerated approval as suggested in the ADL may not result in the most rapid development path for veverimer. For example, the OND suggested that Tricida meet with the Division of Cardiology and Nephrology (the Division) to discuss submission of 52-week serum bicarbonate results from the fully randomized VALOR-CKD trial and that such submission should include a substantial proportion of U.S. and “U.S.-like” patients. The OND also indicated that, if the results of this trial were to demonstrate a meaningfully larger treatment effect on serum bicarbonate than seen in the TRCA-301/TRCA-301E trial, results from VALOR-CKD, along with the results from the TRCA-301/TRCA-301E trial, could address the deficiencies identified in the CRL. However, the OND noted that whether these data would support accelerated approval would remain a review issue and therefore would be subject to the Division’s assessment of the adequacy of the magnitude of increase in serum bicarbonate. Moreover, based on the concerns expressed, we believe that the FDA could require an additional trial or trials to confirm the magnitude, durability of effect or applicability to the U.S. population for resubmission of the veverimer NDA through the Accelerated Approval Program.

Given the feedback provided by the FDA in the ADL, Tricida intends to continue the VALOR-CKD trial without further modifications at the present time with consideration of both the accelerated and traditional approval pathways. Tricida’s planned interim analyses in the VALOR-CKD trial could result in early stopping for efficacy and resubmission of the NDA through a traditional approval pathway with a potential indication of treatment of metabolic acidosis to slow CKD progression. Tricida is also evaluating several options with respect to the VALOR-CKD trial that are focused on obtaining additional data prior to the end of 2022 on the effect of veverimer on (1) CKD progression; (2) physical functioning; and (3) serum bicarbonate. These options include the possibility of stopping the trial early for administrative reasons, which would allow analysis of the data using all alpha remaining at that time. In any event, Tricida believes data from VALOR-CKD will be very important in furthering the understanding of the regulatory path for approval of veverimer.

https://finance.yahoo.com/news/tricida-provides-fda-interactions-210500860.html