Tricida Inc., as expected, said the FDA declined to approve its NDA for veverimer as a treatment for chronic metabolic acidosis due to deficiencies in the NDA.

With an Aug. 22 PDUFA date set and publicly forecasted by the company in July, the turn had already driven company shares (NASDAQ:TCDA) down 40.3%. On Monday morning, shortly after the market opened, shares sagged another 12%.

The FDA provided options for the company to resolve deficiencies the agency noted, which include the possibility that another clinical trial may be needed for approval. The NDA was reviewed under the Accelerated Approval Program and the FDA left that option on the table.

Tricida said it will ask for a type A meeting, usually set within 30 days of the request, then detail its next steps, including a potential NDA resubmission, before 2020 ends.

The FDA accepted veverimer’s NDA for its accelerated approval program in November 2019 based on strong phase III extension data released in March 2019.

Results from Tricida's phase III, 12-week efficacy trial, TRCA-301, and a follow-on 40-week extension trial, TRCA-301E, formed the primary basis of its NDA submission. Both studies met their primary and secondary endpoints.

The CRL specifically noted the need for more data beyond the TRCA-301 and TRCA-301E trials regarding the treatment’s magnitude and durability of veverimer on the surrogate marker of serum bicarbonate and the applicability of the treatment effect to the U.S. population. The FDA also is concerned if the demonstrated effect size would be reasonably likely to predict clinical benefit.

There were no safety, clinical pharmacology/biopharmaceutics, CMC or non-clinical issues identified in the CRL, Tricida said.

Cowen analyst Phil Nadeau wrote Aug. 6, before the FDA specific concerns were revealed, that a CRL would mean at least a year’s delay to the launch.

This is the second, though more consequential, time that Tricida and the agency failed to see eye to eye. In a late cycle meeting with the regulator, held in May, company representatives addressed two substantive review issues that agency reviewers had raised in advance of the meeting, Tricida said in a recent SEC filing. In particular, the FDA expressed concerns related to the magnitude and durability of the treatment effect on the surrogate marker of serum bicarbonate demonstrated in the '301 and '301E trials and the applicability of data from those trials to the U.S. population.

Tricida's team presented its rationale for why they believe their data addressed the issues raised. But because the regulator's July 14 notification about NDA deficiencies didn't specify the issues the agency saw in the application, they were left uncertain what the identified deficiencies were or whether they were related to the review issues raised earlier.

The extension trial followed the 12-week TRCA-301 study of 217 randomized patients with non-dialysis-dependent CKD and metabolic acidosis. Of 208 patients completing the trial, 196 opted to continue with the extension. They were assigned to the same blinded treatment received in the parent trial, with 114 receiving TRC-101 and 82 receiving placebo, of which 111 and 74, respectively, completed one year of treatment.

Chronic kidney disease treatments brought in $12.9 billion in the U.S., western Europe and Japan in 2015 and that market is expected to grow to $21.9 billion by 2025, according to DRG.

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